96 results on '"Xiao, Xiaohe"'
Search Results
2. Flavonoid extracted from Epimedium attenuate cGAS‐STING‐mediated diseases by targeting the formation of functional STING signalosome.
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Wang, Yan, Xu, Guang, Wen, Jincai, Zhao, Xiaomei, Zhao, Huanying, Lv, Guiji, Xu, Yingjie, Xiu, Ye, Li, Junjie, Chen, Simin, Yao, Qing, Chen, Yuanyuan, Ma, Lina, Xiao, Xiaohe, Cao, Junling, and Bai, Zhaofang
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FLAVONOIDS , *MONONUCLEAR leukocytes , *EPIMEDIUM , *INTERFERON regulatory factors , *TYPE I interferons , *CHOLINE - Abstract
Hyperactivation of the cyclic‐GMP‐AMP synthase (cGAS)–stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS‐STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti‐inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow‐derived macrophages (BMDMs), THP‐1 (Tohoku Hospital Pediatrics‐1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS‐STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN‐β, CXCL10 and ISG15) and pro‐inflammatory cytokines (IL‐6 and TNF‐α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK‐binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS‐STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non‐alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS‐STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS‐STING signalling pathway. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Icariside I reduces breast cancer proliferation, apoptosis, invasion, and metastasis probably through inhibiting IL-6/STAT3 signaling pathway.
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Hou, Manting, Li, Hui, He, Tingting, Hui, Siwen, Dai, Wenzhang, Hou, Xiaorong, Zhao, Jing, Zhao, Jia, Wen, Jincai, Kan, Wen, Xiao, Xiaohe, Zhan, Xiaoyan, and Bai, Zhaofang
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BREAST cancer , *METASTATIC breast cancer , *MULTINUCLEATED giant cells , *CELLULAR signal transduction , *CANCER cell growth , *BREAST - Abstract
Objectives: Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism. Methods: Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer. Key findings: EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group. Conclusions: These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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4. The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages.
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Wu, Zhixin, Zhao, Xiaomei, Li, Ruisheng, Wen, Xinru, Xiu, Ye, Long, Minjuan, Li, Junjie, Huang, Xiuqin, Wen, Jincai, Dong, Xu, Xu, Yingjie, Bai, Zhaofang, Zhan, Xiaoyan, and Xiao, Xiaohe
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CHINESE medicine , *COMBINATION drug therapy , *IN vitro studies , *MACROPHAGES , *RESEARCH funding , *HERBAL medicine , *PHARMACEUTICAL chemistry , *POLYMERASE chain reaction , *CHRONIC hepatitis B , *CELLULAR signal transduction , *DNA , *ANTIVIRAL agents , *FLAVONES , *DRUG tablets , *MICE , *VIRAL antigens , *LIGNANS , *ANIMAL experimentation , *WESTERN immunoblotting , *DRUG synergism , *DRUG dosage , *THERAPEUTICS , *PHARMACODYNAMICS , *DRUG administration - Abstract
Background: HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. Methods: Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. Results: In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. Conclusion: Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.
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Xu, Mengwei, Bai, Zhaofang, Xie, Baocheng, Peng, Rui, Du, Ziwei, Liu, Yan, Zhang, Guangshuai, Yan, Si, Xiao, Xiaohe, and Qin, Shuanglin
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DRUG discovery , *MARINE natural products , *DRUG development , *ANTINEOPLASTIC agents , *ACUTE myeloid leukemia , *MARINE toxins - Abstract
Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin entered clinical practice, but there is also a successfully marketed marine-derived bisindole compound called midostaurin that is used for the treatment of acute myeloid leukemia. In summary, investigations into the biological activity and clinical progress of marine-derived bisindoles have revealed their remarkable selectivity, minimal toxicity, and efficacy against various cancer cells. Consequently, they exhibit immense potential in the field of anti-tumor drug development, especially in the field of anti-tumor drug resistance. In the future, these compounds may serve as promising leads in the discovery and development of novel cancer therapeutics. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Glabridin improves autoimmune disease in Trex1-deficient mice by reducing type I interferon production.
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Wen, Jincai, Mu, Wenqing, Li, Hui, Yan, Yulu, Zhan, Xiaoyan, Luo, Wei, Wang, Zhongxia, Kan, Wen, Zhao, Jia, Hui, Siwen, He, Ping, Qin, Shuanglin, Xu, Yingjie, Zhang, Ping, Xiao, Xiaohe, Xu, Guang, and Bai, Zhaofang
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TYPE I interferons , *AUTOIMMUNE diseases , *MONONUCLEAR leukocytes , *CELLULAR signal transduction - Abstract
Background: The cGAS-STING signaling pathway is an essential section of the natural immune system. In recent years, an increasing number of studies have shown a strong link between abnormal activation of the cGAS-STING signaling pathway, a natural immune pathway mediated by the nucleic acid receptor cGAS, and the development and progression of autoimmune diseases. Therefore, it is important to identify an effective compound to specifically downregulate this pathway for disease. Methods: The effect of Glabridin (Glab) was investigated in BMDMs and Peripheral blood mononuclear cell (PBMC) by establishing an in vitro model of cGAS-STING signaling pathway activation. An activation model stimulated by DMXAA was also established in mice to study the effect of Glab. On the other hand, we investigated the possible mechanism of action of Glab and the effect of Glab on Trex1-deficient mice. Results: In this research, we report that Glab, a major component of licorice, specifically inhibits the cGAS-STING signaling pathway by inhibiting the level of type I interferon and inflammatory cytokines (IL-6 and TNF-α). In addition, Glab has a therapeutic effect on innate immune diseases caused by abnormal cytoplasmic DNA in Trex1-deficient mice. Mechanistically, Glab can specifically inhibit the interaction of STING with IRF3. Conclusion: Glab is a specific inhibitor of the cGAS-STING signaling pathway and may be used in the clinical therapy of cGAS-STING pathway-mediated autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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7. The role of Traditional Chinese medicine in anti-HBV: background, progress, and challenges.
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Ge, Feilin, Yang, Yan, Bai, Zhaofang, Si, Lanlan, Wang, Xuemei, Yu, Jia, Xiao, Xiaohe, Liu, Yan, and Ren, Zhigang
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PHYTOTHERAPY , *HEPATITIS B , *ANTI-HIV agents , *AUTOPHAGY , *ANTIVIRAL agents , *HUMAN life cycle , *APOPTOSIS , *IMMUNE system , *HEPATITIS viruses , *DRUG resistance , *NUCLEOTIDES , *OXIDATIVE stress , *VIREMIA , *PLANT extracts , *ALTERNATIVE medicine , *CHINESE medicine , *PHARMACODYNAMICS - Abstract
Chronic hepatitis B (CHB) remains a major world's most serious public health issues. Despite the remarkable effect of nucleos(t)ide analogues (NAs) in inhibiting hepatitis B virus (HBV) deoxyribonucleic acid (DNA) as the first-line drug, there are several limitations still, such as poor antigen inhibition, drug resistance, low-level viremia, restricting patients' functional cure. Due to the constraints of NAs, traditional medicines, such as traditional Chinese medicine (TCM), have become more prevalently used and researched in the clinical treatment of CHB as complementary alternative therapies. As a consequence, the review focuses on the background based on HBV's life cycle as well as the NAs' limitations, progress based on direct and indirect pathway of targeting HBV of TCM, and challenges of TCM. We found TCMs play an increasingly important role in anti-HBV. In a direct antiviral way, they regulate HBV infection, replication, assembly, and other aspects of the HBV life cycle. As for indirect way, TCMs can exert anti-HBV effects through targeting the host, including immune regulation, apoptosis, autophagy, oxidative stress, etc. Especially, TCMs have the advantages of strong antigenic inhibition compared to NAs. Specifically, we can combine the benefits of TCMs in strong HBV antigen inhibition with the benefits of NAs in targeted antiviral effects, in order to find a suitable combination of "TCM + NAs" to contribute to Chinese knowledge of the realisation of the "global elimination of HBV by 2030" goal of the World Health Organization. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Novel role for epalrestat: protecting against NLRP3 inflammasome-driven NASH by targeting aldose reductase.
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Shi, Wei, Xu, Guang, Gao, Yuan, Zhao, Jun, Liu, Tingting, Zhao, Jia, Yang, Huijie, Wei, Ziying, Li, Hui, Xu, An-Long, Bai, Zhaofang, and Xiao, Xiaohe
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REDUCTASE inhibitors , *ALDOSE reductase , *NLRP3 protein , *NON-alcoholic fatty liver disease , *HEPATITIS - Abstract
Background: Nonalcoholic steatohepatitis (NASH) is a progressive and inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocellular injury, inflammation, and fibrosis in various stages. More than 20% of patients with NASH will progress to cirrhosis. Currently, there is a lack of clinically effective drugs for treating NASH, as improving liver histology in NASH is difficult to achieve and maintain through weight loss alone. Hence, the present study aimed to investigate potential therapeutic drugs for NASH. Methods: BMDMs and THP1 cells were used to construct an inflammasome activation model, and then we evaluated the effect of epalrestat on the NLRP3 inflammasome activation. Western blot, real-time qPCR, flow cytometry, and ELISA were used to evaluate the mechanism of epalrestat on NLRP3 inflammasome activation. Next, MCD-induced NASH models were used to evaluate the therapeutic effects of epalrestat in vivo. In addition, to evaluate the safety of epalrestat in vivo, mice were gavaged with epalrestat daily for 14 days. Results: Epalrestat, a clinically effective and safe drug, inhibits NLRP3 inflammasome activation by acting upstream of caspase-1 and inducing ASC oligomerization. Importantly, epalrestat exerts its inhibitory effect on NLRP3 inflammasome activation by inhibiting the activation of aldose reductase. Further investigation revealed that the administration of epalrestat inhibited NLRP3 inflammasome activation in vivo, alleviating liver inflammation and improving NASH pathology. Conclusions: Our study indicated that epalrestat, an aldose reductase inhibitor, effectively suppressed NLRP3 inflammasome activation in vivo and in vitro and might be a new therapeutic approach for NASH. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Novel role for epalrestat: protecting against NLRP3 inflammasome-driven NASH by targeting aldose reductase.
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Shi, Wei, Xu, Guang, Gao, Yuan, Zhao, Jun, Liu, Tingting, Zhao, Jia, Yang, Huijie, Wei, Ziying, Li, Hui, Xu, An-Long, Bai, Zhaofang, and Xiao, Xiaohe
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REDUCTASE inhibitors , *ALDOSE reductase , *NLRP3 protein , *NON-alcoholic fatty liver disease , *HEPATITIS - Abstract
Background: Nonalcoholic steatohepatitis (NASH) is a progressive and inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocellular injury, inflammation, and fibrosis in various stages. More than 20% of patients with NASH will progress to cirrhosis. Currently, there is a lack of clinically effective drugs for treating NASH, as improving liver histology in NASH is difficult to achieve and maintain through weight loss alone. Hence, the present study aimed to investigate potential therapeutic drugs for NASH. Methods: BMDMs and THP1 cells were used to construct an inflammasome activation model, and then we evaluated the effect of epalrestat on the NLRP3 inflammasome activation. Western blot, real-time qPCR, flow cytometry, and ELISA were used to evaluate the mechanism of epalrestat on NLRP3 inflammasome activation. Next, MCD-induced NASH models were used to evaluate the therapeutic effects of epalrestat in vivo. In addition, to evaluate the safety of epalrestat in vivo, mice were gavaged with epalrestat daily for 14 days. Results: Epalrestat, a clinically effective and safe drug, inhibits NLRP3 inflammasome activation by acting upstream of caspase-1 and inducing ASC oligomerization. Importantly, epalrestat exerts its inhibitory effect on NLRP3 inflammasome activation by inhibiting the activation of aldose reductase. Further investigation revealed that the administration of epalrestat inhibited NLRP3 inflammasome activation in vivo, alleviating liver inflammation and improving NASH pathology. Conclusions: Our study indicated that epalrestat, an aldose reductase inhibitor, effectively suppressed NLRP3 inflammasome activation in vivo and in vitro and might be a new therapeutic approach for NASH. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Insights on Antitumor Activity and Mechanism of Natural Benzophenanthridine Alkaloids.
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Peng, Rui, Xu, Mengwei, Xie, Baocheng, Min, Qing, Hui, Siwen, Du, Ziwei, Liu, Yan, Yu, Wei, Wang, Shi, Chen, Xin, Yang, Guang, Bai, Zhaofang, Xiao, Xiaohe, and Qin, Shuanglin
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ANTINEOPLASTIC agents , *PHENANTHRIDINE , *ISOQUINOLINE alkaloids , *NATURAL products , *DRUG development , *NEW product development , *STEM cells - Abstract
Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of papaveraceae, corydalis, and rutaceae. Biological activities and clinical studies have shown that benzophenanthridine alkaloids have inhibitory effects on many cancers. Considering that the anticancer activities and mechanisms of many natural benzophenanthridine alkaloids have been discovered in succession, the purpose of this paper is to review the anticancer effects of benzophenanthridine alkaloids and explore the application potential of these natural products in the development of antitumor drugs. A literature survey was carried out using Scopus, Pubmed, Reaxys, and Google Scholar databases. This review summarizes and analyzes the current status of research on the antitumor activity and antitumor mechanism of natural products of benzophenanthridine from different sources. The research progress of the antitumor activity of natural products of benzophenanthridine from 1983 to 2023 was reviewed. The antitumor activities of 90 natural products of benzophenanthridine and their related analogues were summarized, and the results directly or indirectly showed that natural products of benzophenanthridine had the effects of antidrug-resistant tumor cell lines, antitumor stem cells, and inducing ferroptosis. In conclusion, benzophenanthridine alkaloids have inhibitory effects on a variety of cancers and have the potential to counteract tumor resistance, and they have great application potential in the development of antitumor drugs. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC.
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Zhao, Jia, Liu, Hongbin, Hong, Zhixian, Luo, Wei, Mu, Wenqing, Hou, Xiaorong, Xu, Guang, Fang, Zhie, Ren, Lutong, Liu, Tingting, Wen, Jincai, Shi, Wei, Wei, Ziying, Yang, Yongping, Zou, Wenjun, Zhao, Jun, Xiao, Xiaohe, Bai, Zhaofang, and Zhan, Xiaoyan
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NLRP3 protein , *INFLAMMASOMES , *HEPATIC fibrosis , *SEPTIC shock , *NON-alcoholic fatty liver disease - Abstract
Background: Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study. Methods: IL-1β and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1β levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry. Results: Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH. Conclusions: Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation.
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Mu, Wenqing, Xu, Guang, Wang, Zhilei, Li, Qiang, Sun, Siqiao, Qin, Qin, Li, Zhiyong, Shi, Wei, Dai, Wenzhang, Zhan, Xiaoyan, Wang, Jiabo, Bai, Zhaofang, and Xiao, Xiaohe
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TRICYCLIC antidepressants , *NLRP3 protein , *HEPATITIS , *INFLAMMASOMES , *REACTIVE oxygen species , *ANTIDEPRESSANTS - Abstract
Background: Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood. Methods: We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3−/−) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3−/− mice. Results: We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events. Conclusion: Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury. DBhggTBWtuReWsEtfqqAGm Video Abstract [ABSTRACT FROM AUTHOR]
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- 2023
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13. Pharmacovigilance in China: Evolution and future challenges.
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Song, Haibo, Pei, Xiaojing, Liu, Zuoxiang, Shen, Chuanyong, Sun, Jun, Liu, Yuqin, Zhou, Lingyun, Sun, Feng, and Xiao, Xiaohe
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MEDICATION safety , *ORPHAN drugs , *WATCHFUL waiting , *TOTAL quality management , *MARKETING , *MEDICAL schools - Abstract
Drug‐related adverse reactions are among the main reasons for harm to patients under care worldwide and even their deaths. The pharmacovigilance system has been proven to be an effective method of avoiding or alleviating such adverse events. In 2019, after two decades of implementation of the drug‐related adverse reaction reporting system, China formally implemented a pharmacovigilance system with the Pharmacovigilance Quality Management Standards and a series of supporting technical documents created to improve the safety of medication given to patients. China's pharmacovigilance system has faced many problems and challenges during its implementation. This spontaneous reporting system is the main source of data for China's medication vigilance activities, but it has not provided sufficiently powerful evidence for regulatory decision‐making. In conformity with the health‐centred drug regulatory concept, the Chinese government has accelerated the speed of examination and approval of urgently needed clinical drugs and orphan drugs along with the requirement to improve the safety supervision of these drugs after their listing. China's marketing authorization holders (MAHs) must strengthen their pharmacovigilance capabilities as the primary responsible departments for drug safety. Chinese medical schools generally lack professional courses on pharmacovigilance. The regulatory authorities have recognized such problems and have made efforts to improve the professional capacity of pharmacovigilance personnel and to strengthen cooperation with stakeholders through the implementation of an action plan of medication surveillance and the establishment of a patient‐based adverse events reporting system and active surveillance systems, which will help China bridge the gap to bring its pharmacovigilance practice up to standards. [ABSTRACT FROM AUTHOR]
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- 2023
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14. A multi-omics study reveals the therapeutic effect of Linderae Radix water extract on irritable bowel syndrome (IBS-D).
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Ouyang, Linqi, Liu, Tao, He, Yang, He, Yiran, Xu, Wenfeng, Deng, Guoyan, Deng, Guiming, and Xiao, Xiaohe
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CYSTEINE metabolism , *METHIONINE metabolism , *CHINESE medicine , *DIARRHEA , *CECUM diseases , *IRRITABLE colon , *DATA analysis , *MULTIOMICS , *GUT microbiome , *TREATMENT effectiveness , *RATS , *RNA , *GENE expression , *METABOLITES , *BACTERIA , *PAIN management , *ANIMAL experimentation , *DICARBOXYLIC acids , *STATISTICS , *METABOLOMICS , *GASTROINTESTINAL diseases , *SEQUENCE analysis , *BIOMARKERS - Abstract
Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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15. Liuweiwuling Tablet relieves the inflammatory transformation of hepatocellular carcinoma by inhibiting the PI3K/AKT/NF-κB signaling pathway.
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Chen, Yuanyuan, Song, Zheng, Hou, Xiaorong, Liu, Jia, Zheng, Congyang, Zhao, Xiaomei, Lv, Guiji, Li, Junjie, Xiu, Ye, Shi, Wei, Zhao, Jia, Yang, Huijie, Wang, Yan, Zhao, Jun, Zhan, Xiaoyan, Niu, Ming, Zou, Wenjun, Bai, Zhaofang, and Xiao, Xiaohe
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BLOOD testing , *ALKALINE phosphatase , *GAMMA-glutamyltransferase , *FLOW cytometry , *HERBAL medicine , *IN vivo studies , *STAINS & staining (Microscopy) , *SEQUENCE analysis , *ANIMAL experimentation , *NITROSOAMINES , *WESTERN immunoblotting , *NEOPLASTIC cell transformation , *HEPATITIS , *NF-kappa B , *MACROPHAGES , *CIRRHOSIS of the liver , *APOPTOSIS , *CELLULAR signal transduction , *RATS , *SEVERITY of illness index , *GENE expression , *TRANSFERASES , *GENE expression profiling , *ENZYME-linked immunosorbent assay , *CELL proliferation , *INFLAMMATORY mediators , *CELL lines , *POLYMERASE chain reaction , *PHARMACEUTICAL chemistry , *CALCIUM-binding proteins , *CHINESE medicine , *HEPATOCELLULAR carcinoma , *ASPARTATE aminotransferase , *ALANINE aminotransferase , *PHARMACODYNAMICS , *DISEASE risk factors - Abstract
Liuweiwuling Tablet (LWWL) is a patented Chinese medicine approved by the Chinese National Medical Products Administration (NMPA). Clinically, it is used to treat a range of liver diseases that precede hepatocellular carcinoma (HCC), including hepatitis, liver fibrosis and cirrhosis. LWWL is hypothesized to inhibit the inflammatory transformation of HCC, which may have a positive impact on the prevention and treatment of HCC. However, its exact mechanism of action remains unknown. To investigate how LWWL is effective in the treatment of HCC and to validate the pathways involved in this process. An in vivo model of HCC induced by diethylnitrosamine (DEN) was established to study the effect of LWWL on the development of HCC. The rat serum was analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT). The rat liver tissues were stained with hematoxylin and eosin (HE) and Masson's trichrome for pathological analysis. Rat liver tissue was subjected to transcriptome sequencing. Expression of inflammatory and liver fibrosis-related factors in bone marrow-derived macrophages (BMDMs) and LX-2 cells was detected by QRT-PCR, ELISA and Western blot (WB). The expression of apoptosis and stemness genes in HepG2 and Huh7 cells was assessed through flow cytometry and QRT-PCR. Transcriptomics, network pharmacology, WB, and QRT-PCR were employed to validate the mechanisms associated with the amelioration of HCC development by LWWL. LWWL significantly reduced the severity of hepatitis and liver fibrosis, the expression of tumor stemness genes, and the incidence of HCC. In addition, LWWL inhibited the release of inflammatory substances and nuclear accumulation of P65 protein in BMDMs as well as the conversion of LX-2 cells to fibroblasts. LWWL inhibited the proliferation of HepG2 and Huh7 cells, including the initiation of apoptosis and the reduction of stemness gene expression. Importantly, LWWL regulates the PI3K/AKT/NF-κB pathway, which affects hepatic inflammation and cancer progression. LWWL inhibited the occurrence and development of HCC by modulating the severity of hepatitis and liver fibrosis, indicating the potential clinical relevance of LWWL in preventing and treating HCC. [Display omitted] • Potential efficacy of LWWL in chemically related hepatocellular carcinoma. • LWWL inhibits the development of the hepatitis-fibrosis-HCC axis. • A key mechanism of LWWL is the PI3K/AKT/NF-κB signalling pathway. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer's disease.
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Chen, Xu-Jia, Deng, Zhou, Zhang, Le-Le, Pan, Yan, Fu, Jia, Zou, Liang, Bai, Zhaofang, Xiao, Xiaohe, and Sheng, Feiya
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ALZHEIMER'S disease , *GANODERMA lucidum , *NEURODEGENERATION , *MUSHROOMS , *MEMORY loss - Abstract
Alzheimer's disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Aβ formation, affecting activated microglia, regulating NF-κB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD. [Display omitted] • G. lucidum exhibits therapeutic potential against Alzheimer's disease. • Polysaccharides and triterpenes represent main bioactive components of G. lucidum. • G. lucidum has a good safety profile within reasonable dosage ranges. • G. lucidum and its components can target multiple aspects of AD pathology. [ABSTRACT FROM AUTHOR]
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- 2024
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17. LicochalconeB inhibits cGAS-STING signaling pathway and prevents autoimmunity diseases.
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Luo, Wei, Song, Zheng, Xu, Guang, Wang, Hongbo, Mu, Wenqing, Wen, Jincai, Zhang, Ping, Qin, Shuanglin, Xiao, Xiaohe, and Bai, Zhaofang
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TYPE I interferons , *CELLULAR signal transduction , *AUTOIMMUNITY , *PSEUDOPOTENTIAL method - Abstract
• LicoB is a potential and effective cGAS-STING signaling pathway inhibitor. • LicoB affected the STING-TBK1-IRF3 signal axis. • LicoB effectively diminished systemic inflammation in Trex1-/- mice. Cytosolic DNA activates the STING (stimulator of interferon genes) signaling pathway to trigger interferon and inflammatory responses that protect against microbial infections and cancer. However, Aicardi–Goutières syndrome (AGS) persistently activates the STING signaling pathway, which can lead to severe autoimmune diseases. We demonstrate herein that Licochalcone B (LicoB), the main component of traditional licorice, is an inhibitor of the STING signaling pathway. We observed that LicoB inhibited the activation of the STING signaling pathway in macrophages. Mechanically, LicoB affected the STING-TBK1-IRF3 signal axis and inhibited the activation of the STING downstream signaling pathway. Furthermore, LicoB inhibited the increase in type I interferon levels in mice induced by the STING agonist CMA. LicoB significantly reduced systemic inflammation in Trex1−/− mice. Our results show that LicoB, a STING signaling pathway inhibitor, is a promising candidate for the treatment of diseases related to STING signaling pathway activation. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs.
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Zhou, Yongfeng, Wang, Junnan, Zhang, Dingkun, Liu, Jiaxin, Wu, Qinghua, Chen, Jiang, Tan, Peng, Xing, Boyu, Han, Yanzhong, Zhang, Ping, Xiao, Xiaohe, and Pei, Jin
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HERBAL medicine , *ORGANIC compounds , *DRUG design , *LIVER diseases , *HEPATOTOXICOLOGY , *MOLECULAR structure - Abstract
Drug-induced liver injury (DILI) is a common adverse drug reaction (ADR) and a serious threat to health that affects disease treatments. At present, no targeted clinical drugs are available for DILI. Traditional natural medicines have been widely used as health products. Some natural medicines exert specific hepatoprotective effects, with few side effects and significant clinical efficacy. Thus, natural medicines may be a promising direction for DILI treatment. In this review, we summarize the current knowledge, common drugs and mechanisms of DILI, as well as the clinical trials of natural drugs and their bioactive components in anticipation of the future development of potential hepatoprotective drugs. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Establishment of an anti-inflammation-based bioassay for the quality control of the 13-component TCM formula (Lianhua Qingwen).
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Chen, Shuaishuai, Yang, Xiaojuan, Wei, Ziying, Zhang, Yanru, Huang, Ying, Shi, Zhuo, Zhang, Ziteng, Wang, Jiabo, Zhang, Haizhu, Ma, Jianli, Xiao, Xiaohe, and Niu, Ming
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BIOLOGICAL assay , *QUALITY control , *CHINESE medicine - Abstract
Owing to the complexity of chemical ingredients in traditional Chinese medicine (TCM), it is difficult to maintain quality and efficacy by relying only on chemical markers. Lianhua Qingwen capsule (LHQW) was selected as an example to discuss the feasibility of a bioassay for quality control. Network pharmacology was used to screen potential targets in LHQW with respect to its anti-inflammatory effects. An in vitro cell model was used to validate the prediction. An anti-inflammatory bioassay was established for the quality evaluation of LHQW in 40 batches of marketed products and three batches of destructed samples. The tumor necrosis factor/interleukin-6 (TNF/IL-6) pathway via macrophage was selected as the potential target of LHQW. The IC50 value of LHQW on RAW 264.7 was 799.8 μg/mL. LHQW had significant inhibitory effects on the expression of IL-6 in a dose-dependent manner (p < 0.05). The anti-inflammatory biopotency of LHQW was calculated based on the inhibitory bioactivity on IL-6. The biopotency of 40 marketed samples ranged from 404 U/μg to 2171 U/μg, with a coefficient of variation (CV) of 37.91%. By contrast, the contents of forsythin indicated lower CV (28.05%) than the value of biopotency. Moreover, the biopotencies of destructed samples declined approximate 50%, while the contents of forsythin did not change. This newly established bioassay revealed a better ability to discriminate the quality variations of LHQW as compared to the routine chemical determination. A well-established bioassay may have promising ability to reveal the variance in quality of TCM. [ABSTRACT FROM AUTHOR]
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- 2021
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20. Assessment of the toxicity of two Aconitum herbal medicines by microcalorimetry and chemometrics
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Kong, Weijun, Wang, Jiabo, Xiao, Xiaohe, Zang, Qingce, Zhao, Yanling, Wei, Jianhe, Chen, Shilin, and Yang, Meihua
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HERBAL medicine , *MONKSHOODS , *CALORIMETRY , *CHEMOMETRICS , *SHIGELLA , *DRUG toxicity , *FOOD chemistry - Abstract
Abstract: In this study, a non-invasive and non-destructive microcalorimetric method was applied to assess the toxic effects of two Aconitum herbal medicines, Radix Aconitum Kusnezoffii and Radix A. carmichaeli, on the multiplying and non-multiplying metabolism of Shigella dysenteriae. Some crucial information, such as the thermogenic curves and thermo-kinetic parameters including growth rate constant k, inhibitory ratio I and half-inhibitory concentration IC 50, of S. dysenteriae growth affected by the two Aconitum species was obtained. Coupled with chemometric analysis on this information, it could be found that Radix A. Kusnezoffii and Radix A. carmichaeli could be differentiated according to their toxic effects; Radix A. Kusnezoffii with IC 50 of 35.2mg/mL had stronger toxic effect than Radix A. carmichaeli with IC 50 of 49.6mg/mL. This present study shows the effectiveness of combining microcalorimetry and chemometrics for assessing the toxic effects of herbal medicines and other food matrices. [Copyright &y& Elsevier]
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- 2012
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21. Comparative study of effects of two bile acid derivatives on Staphylococcus aureus by multiple analytical methods
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Kong, Weijun, Jin, Cheng, Xiao, Xiaohe, Zhao, Yanling, Li, Zulun, Zhang, Ping, Liu, Wei, and Li, Xing-Feng
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BILE acids , *STAPHYLOCOCCUS aureus , *COMPARATIVE studies , *CHOLIC acid , *CALORIMETRY , *TOXICITY testing , *PRINCIPAL components analysis , *MULTIVARIATE analysis - Abstract
Abstract: The effects of two bile acid derivatives, cholic acid (CA) and deoxycholic acid (DCA) on Staphylococcus aureus (S. aureus) growth were investigated and compared by microcalorimetry coupled with multiple analytical methods. The heat power (HP)–time curves of S. aureus growth affected by CA and DCA were studied by similarity analysis (SA), respectively. Then the quantitative thermo-kinetic parameters obtained from these curves were investigated by the multivariate analysis of variance (MANOVA) and principal component analysis (PCA). By analyzing the two main parameters, growth rate constant k 2 of the second exponential phase and the heat power P 2 of the second highest peak, together with the minimum inhibitory concentration (MIC) values of 10μg/mL for CA and 20μg/mL for DCA, it could be concluded that the antibacterial effect of CA was stronger than that of DCA. The existence of α-OH at C-7 position of steroid nucleus of bile acid derivatives enhanced the hydrophilicity of compound CA and its inhibitory effect on S. aureus. This study provides a useful method and idea to accurately evaluate the antibacterial effects of bile acid derivatives, which provides some references for screening out new antibacterial agents with high efficacy and low toxicity. [Copyright &y& Elsevier]
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- 2010
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22. Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats
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Wang, Jiabo, Zhao, Yanling, Xiao, Xiaohe, Li, Huifang, Zhao, Haiping, Zhang, Ping, and Jin, Cheng
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TREATMENT of chronic kidney failure , *HEPATOTOXICOLOGY , *RHUBARB , *PLANT extracts , *LABORATORY rats , *CHINESE medicine , *ANTHRAQUINONES , *NEPHROTOXICOLOGY - Abstract
Abstract: Aim of the study: Rhubarb is well used to treat chronic renal failure (CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF. Materials and methods: Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract. Results: In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage. Conclusions: After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats. [Copyright &y& Elsevier]
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- 2009
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23. Microcalorimetric investigation of effect of berberine alkaloids from Coptis chinensis Franch on intestinal diagnostic flora growth.
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Yan Dan, Wei Li, Xiao XiaoHe, DanLei, Zhou, and YuMei, Han
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BERBERINE , *CALORIMETERS , *COPTIS chinensis , *BIFIDOBACTERIUM , *ESCHERICHIA coli , *ALKALOIDS - Abstract
The inhibitory effect of three berberine alkaloids (BAs) from Coptis chinensis Franch, a traditional Chinese medicinal (TCM) herb, on Bifldobacterium adolescentis growth was investigated by microcalorimetry. The power-time curves of B. adolescentis with and without BAs were acquired, meanwhile the extent and duration of inhibitory effect on the metabolism were evaluated by the growth rate constant (k), half inhibitory ratio (IC[sub50]), maximum heat-output power (Pmax), peak time of maximum heat-output power (t[subp]) and total heat production (Q[subt]). k, P[subma]x and Q[subt] decreased, and t[subp] was prolonged with the increase of BAs concentration. The IC[sub50] of BAs is 806 μg/mL for berberine, 341 μg/mL for coptisine and 236 μg/mL for palmatine. The sequence of antimicrobial activity of BAs is berberine < coptisine < palmatine. Combined with previous studies, it could be shown that the sequences of antimicrobial activity of BAs on both Bacillus shigae and Escherichla coil are berberine > coptisine > palmatine. The structure-function relationship of BAs indicates that the functional group methylenedioxy or methoxyl at C2 and C3 might be the major group inducing the activities of BAs on E. coil and B. adolescentis. Meanwhile, the substituent groups at C2, C3, C9 and C10 almost have equal effect on B. shigae. [ABSTRACT FROM AUTHOR]
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- 2009
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24. Brevilin A inhibits NLRP3 inflammasome activation in vivo and in vitro by acting on the upstream of NLRP3-induced ASC oligomerization.
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Qin, Qin, Xu, Guang, Zhan, Xiaoyan, Wang, Zhilei, Wang, Yan, Liu, Hongbin, Hou, Xiaorong, Shi, Wei, Ma, Jianli, Bai, Zhaofang, and Xiao, Xiaohe
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INFLAMMASOMES , *NLRP3 protein , *LABORATORY mice , *OLIGOMERIZATION , *CASPASES - Abstract
• BA selectively inhibits NLRP3 inflammasome activation by acting on the upstream of ASC oligomerization. • BA attenuates NLRP3 inflammasome activation in LPS-mediated inflammation and MSU-induced peritonitis mouse model. • BA can serve as a drug candidate for NLRP3 inflammasome-driven diseases. Brevilin A (BA), is a natural biologically active ingredient derived from Centipeda minima with several reports of anti-cancer, while its anti-inflammatory activity is rarely reported. Current studies have found the dysregulated activation of NLRP3 inflammasome cause a variety of inflammatory diseases. Targeting the NLRP3 inflammasome contributes to the treatment of NLRP3-induced diseases. Here, we found that BA significantly attenuates the activation of caspase-1 and the subsequent secretion of the interleukin-1β (IL-1β) in mouse macrophages and human THP-1 cells, showing the inhibitory effect of BA on the NLRP3 inflammasome activation. Moreover, BA specifically inhibits NLRs inflammasomes activation triggered by multi-stimuli, but it has no effect on the AIM2 inflammasome activation, indicating that BA is a specific inhibitor of the NLRs inflammasomes. Research on the mechanism found BA inhibits NLRP3 inflammasome activation by blocking the upstream of ASC oligomerization. Importantly, in vivo experiments showed that BA markedly reduces the secretion of IL-1β to suppress NLRP3 inflammasome in the LPS-induced inflammation and MSU-challenged peritonitis model. In conclusion, our experiments show that BA is an effective NLRP3 inflammasome inhibitor and can be regarded as a drug candidate for NLRP3 inflammasome-driven diseases. [ABSTRACT FROM AUTHOR]
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- 2021
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25. Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity.
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Gao, Yuan, Xu, Guang, Ma, Li, Shi, Wei, Wang, Zhilei, Zhan, Xiaoyan, Qin, Nan, He, Tingting, Guo, Yuming, Niu, Ming, Wang, Jiabo, Bai, Zhaofang, and Xiao, Xiaohe
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HEPATOTOXICOLOGY , *REACTIVE oxygen species , *LACTATE dehydrogenase , *LIVER injuries , *JOINT diseases , *JOINTS (Anatomy) - Abstract
Background: Epimedii Folium (EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI. Methods: Bone-marrow-derived macrophages (BMDMs) were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo. Results: Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mouse model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation. Conclusions: Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI. 8Ywwvw_wfGTk5F7e3asboC Video abstract. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Isomaculosidine facilitates NLRP3 inflammasome activation by promoting mitochondrial reactive oxygen species production and causes idiosyncratic liver injury.
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Shi, Wei, Liu, Tingting, Yang, Huijie, Zhao, Jia, Wei, Ziying, Huang, Yujiao, Li, Zhiyong, Li, Hui, Liang, Longxin, Hou, Xiaorong, Chen, Yuanyuan, Gao, Yuan, Bai, Zhaofang, and Xiao, Xiaohe
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IN vitro studies , *FLOW cytometry , *DRUG efficacy , *MEDICINAL plants , *HERBAL medicine , *IN vivo studies , *ALKALOIDS , *ANIMAL experimentation , *WESTERN immunoblotting , *SIGNAL peptides , *MACROPHAGES , *LIVER diseases , *HEPATOTOXICOLOGY , *MITOCHONDRIA , *ENZYME-linked immunosorbent assay , *FLUORESCENT antibody technique , *PLANT extracts , *REACTIVE oxygen species , *BONE marrow , *CHINESE medicine , *MICE , *EVALUATION - Abstract
Dictamnus dasycarpus Turcz. (Dictamni Cortex, DC), a Chinese herbal medicine, is commonly used for treating chronic dermatosis and rheumatism, but can also cause herb-induced liver injury (HILI). Our study has demonstrated that DC can induce idiosyncratic HILI, but the mechanism remains unknown. The NLRP3 inflammasome has become a major target for addressing many diseases. The activation of NLRP3 inflammasome is responsible for many liver-related inflammatory diseases, including idiosyncratic HILI. The objective of our study was to demonstrate the mechanism underlying the idiosyncratic HILI induced by DC and clarify the susceptible component in DC. Bone marrow-derived macrophages (BMDMs) and THP1 cells were selected to assess the effect of isomaculosidine (IMD) on NLRP3 inflammasome activation in vitro. Western blot, ELISA and Caspase-Glo® 1 Inflammasome Assay, flow cytometry and Immunofluorescence were employed to detect the mechanism of IMD on NLRP3 inflammasome activation. To assess the efficacy of IMD in vivo , mice were intravenously administrated with LPS and then IMD were injected intraperitoneally for 6 h. The results of our in vitro studies demonstrate that IMD, the major constituent of DC, specifically promoted ATP- and nigericin-induced activation of NLRP3 inflammasome, but not NLRC4 and AIM2 inflammasomes. Additionally, IMD promoted nigericin-induced ASC oligomerization. Notably, synergistic induction of mtROS played a key role on the activation of NLRP3 inflammasome. IMD increased the mtROS production in the activation of NLRP3 inflammasome induced by nigericin. In addition, the results of our in vivo study showed that the combination of nonhepatotoxic doses of LPS and IMD can increase the levels of ALT, AST, and DBIL, leading to liver injury. IMD specifically facilitated the activation of NLRP3 inflammasome induced by nigericin and ATP, which is responsible for DC-induced idiosyncratic HILI. [Display omitted] • IMD enhances NLRP3 inflammasome activation triggered by ATP or nigericin. • The production of mtROS was a key element to the promoting effect of IMD on NLRP3 inflammasome activation. • IMD induces idiosyncratic HILI by promoting NLRP3 inflammasome activation. • IMD is responsible for DC-induced idiosyncratic HILI. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Bavachin combined with epimedin B induce idiosyncratic liver injury under immunological stress conditions.
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Lin, Mengmeng, Li, Yingying, Cao, Bo, Xu, Jing, Zhang, Yujun, Li, Guohui, Xiao, Xiaohe, and Li, Chunyu
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LIVER injuries , *MULTIVARIATE analysis , *GENE expression , *CHINESE medicine , *LIPIDOMICS , *HOMEOSTASIS - Abstract
Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B—two active ingredients derived from both EF and PF—are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2 , Cd74 , Banp , Oas3 , Oas2 , Gbp8 , Slfn8 , Gbp2b , Serpina3g , Zbtb40 , H2-Ab1 , Osgin1 , Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury. [Display omitted] • Bavachin combined with epimedin B-induced IDILI was evaluated under immunological stress conditions. • Integrative lipidomics and transcriptomics approach was used to reveal differential genes and metabolites underlying IDILI. • This study provide fresh insights into unraveling the pathogenesis of IDILI associated with traditional Chinese medicine. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Clinical Efficacy and Safety of Eight Traditional Chinese Medicine Combined with Entecavir in the Treatment of Chronic Hepatitis B Liver Fibrosis in Adults: A Network Meta-Analysis.
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Wang, Tao, Jin, Wei, Huang, Qianqian, Li, Haotian, Zhu, Yun, Liu, Honghong, Cai, Huadan, Wang, Jiabo, Wang, Ruilin, Xiao, Xiaohe, Zhao, Yanling, and Zou, Wenjun
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HERBAL medicine , *LIVER , *CHINESE medicine , *META-analysis , *PATIENT safety , *SYSTEMATIC reviews , *ANTIRETROVIRAL agents , *FIBROSIS , *DATA analysis software , *DESCRIPTIVE statistics , *CHRONIC hepatitis B , *ADULTS - Abstract
Background. Traditional Chinese medicine (TCM) is used as an adjuvant drug for the treatment of chronic hepatitis B liver fibrosis and is used frequently. We still do not know which TCM has the best curative effect as an adjuvant drug. Therefore, we decided to use network meta-analysis to solve this problem. Methods. We used the RevMan software (5.3) and Stata software (13.0) to achieve this network meta-analysis (NMA). The primary outcomes of this study were HA, LN, PCIII, and IV-C; the secondary outcomes of this study were AST, ALT, and HBV-DNA negative conversion rate, and the Cochrane risk-of-bias tool was used to assess the quality of the included studies. For all outcomes, the scissors funnel plot, Egger test, and Begg test were used to detect publication bias, and sensitivity analysis was used to investigate the stability of the results. And the meta-regression was used to explore the source of heterogeneity. Results. A total of 34 articles were included in this study. The study involved a total of 3199 patients, of which 1578 were assigned to the control group and 1621 patients were assigned to the experimental group. The number of men and women is roughly equal, and the average age is about 43 years old. In addition, nine treatment strategies were involved in this study. The combination of TCM and entecavir can significantly improve the patients' HA, LN, PCIII, IV-C, AST, ALT, and HBV-DNA negative conversion rates. The comprehensive evaluation results showed that FHC combined with entecavir has more advantages than other treatment strategies. Conclusion. For improving the HBV-DNA negative conversion rates, adding TCM to the therapeutic strategies does not seem to show absolute superiority. Finally, FHC combined with entecavir is the best therapeutic strategy. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Components synergy between stilbenes and emodin derivatives contributes to hepatotoxicity induced by Polygonum multiflorum.
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Zhang, Le, Liu, Xiaoyi, Tu, Can, Li, Chunyu, Song, Di, Zhu, Jingxiao, Zhou, Yuanyuan, Wang, Xiaohui, Li, Ruisheng, Xiao, Xiaohe, Liu, Youping, and Wang, Jiabo
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EMODIN , *VITAMIN A , *POLYGONUM , *CHINESE medicine , *VITAMIN B6 , *HEPATOTOXICOLOGY , *LIVER injuries - Abstract
Polygonum multiflorum Thunb. (PM) is a famous traditional Chinese medicine with liver tonic effect, but arousing great concerns for hepatotoxicity issue. In this study, we elucidated the contribution of the two major compounds, emodin-8-O-β-D-glucoside (EG) and 2,3,5,4´-tetrahydroxyl diphenylethylene-2-O-glucoside (TSG), in PM-induced liver injury. Based on LC-MS, the two concerned compounds were detected simultaneously in the sera of patients with PM-induced liver injury. In the lipopolysaccharide (LPS)-mediated inflammatory stress rat model, by the analysis of plasma biochemistry and liver histopathology, we observed that the solo treatment of EG, not TSG, could induce significant liver injury; and the combined administration of EG and TSG caused more severe liver injury than that of EG. Metabolomics analysis revealed that the EG-triggered liver injury was associated with significant disturbances of sphingolipids and primary bile acids metabolism pathways. In the combined administration group, much more disturbances in EG-triggered metabolic pathways, as well as alterations of several additional pathways such as retinol metabolism and vitamin B6 metabolism, were observed. Taken together, we considered EG was involved in the idiosyncratic liver injury of PM, and TSG played a synergetic role with EG, which contributed to the understanding of the hepatotoxic basis of PM. [ABSTRACT FROM AUTHOR]
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- 2020
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30. Biothermokinetic characterization and evaluation on the quality of Colla corii asini.
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Liu, Jing, Ma, Li, Li, Yang, Zuo, Xiaobin, Gao, Yuan, Wang, Tao, Zhang, Yan, Liu, Haibin, Wang, Jiabo, Niu, Ming, Liu, Shijing, and Xiao, Xiaohe
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DOSE-effect relationship in pharmacology , *PRINCIPAL components analysis , *ESCHERICHIA coli , *TRADITIONAL medicine - Abstract
Colla corii asini (CCA) is a widely used animal-derived traditional medicine and nutritional supplement in China that has a variety of bioactive effects, especially anti-anaemic effects. To date, the effective substances in CCA are still unclear, thus limiting the evaluation of the quality and consistency of CCA. In this study, a microcalorimetry-based bioassay method was established to assess the quality of CCA by investigating its effects on the growth and metabolism of Escherichia coli, and ten biothermodynamic parameters were employed to characterize the biothermal changes. A principal component analysis (PCA) of these parameters showed that CCA significantly promotes the heat production of E. coli compared to that in the control group, and CCA showed an obvious dose–effect relationship from 0.625 to 20 mg mL−1. Then, the effects of 12 batches of CCA from three different manufacturers were studied at a concentration of 5 mg mL−1, which had a good effect and showed good intraday and daytime reproducibility. The results revealed distinctive characteristics among different manufacturers and good consistency within the same manufacturer according to the scores of the first principal component. In summary, the method based on microcalorimetric has good prospects in the evaluation of the quality of CCA. [ABSTRACT FROM AUTHOR]
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- 2020
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31. Carbamazepine promotes specific stimuli-induced NLRP3 inflammasome activation and causes idiosyncratic liver injury in mice.
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Wang, Zhilei, Xu, Guang, Zhan, Xiaoyan, Liu, Youping, Gao, Yuan, Chen, Nian, Guo, Yuming, Li, Ruisheng, He, Tingting, Song, Xueai, Niu, Ming, Wang, Jiabo, Bai, Zhaofang, and Xiao, Xiaohe
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LIVER injuries , *CARBAMAZEPINE , *LIPOPOLYSACCHARIDES , *PATHOLOGY , *ANTICONVULSANTS , *ADENOSINE triphosphate , *REACTIVE oxygen species , *MEDICATION safety - Abstract
The occurrence of idiosyncratic drug-induced liver injury (IDILI) is a leading cause of post-marketing safety warnings and withdrawals of drugs. Carbamazepine (CBZ), widely used as an antiepileptic agent, could cause rare but severe idiosyncratic liver injury in humans. Although recent studies have shown that inflammasome is implicated in CBZ-induced hepatocellular injury in vitro, the precise pathogenesis of hepatotoxicity remains largely unexplored. Here we report that CBZ causes idiosyncratic liver injury through promoting specific stimuli-induced NLRP3 inflammasome activation. CBZ (40 μM) enhances NLRP3 inflammasome activation triggered by adenosine triphosphate (ATP) or nigericin, rather than SiO2, monosodium urate crystal or intracellular lipopolysaccharide (LPS). In addition, CBZ has no effect on NLRC4 or AIM2 inflammasome activation. Mechanistically, synergistic induction of mitochondrial reactive oxygen species (mtROS) is a crucial event in the enhancement effect of CBZ on ATP- or nigericin-induced NLRP3 inflammasome activation. Moreover, the "C=C" on the seven-membered ring and "C=O" on the nitrogen of CBZ may be contribute to NLRP3 inflammasome hyperactivation and hepatotoxicity. Notably, in vivo data indicate that CBZ (50 mg/kg) causes liver injury in an LPS (2 mg/kg)-mediated susceptibility mouse model of IDILI, accompanied by an increase in caspase-1 activity and IL-1β production, whereas the combination of CBZ and LPS does not exhibit the effect in NLRP3-knockout mice. In conclusion, CBZ specifically promotes ATP- or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic liver injury. Our findings also suggest that CBZ may be avoided in patients with NLRP3 inflammasome activation-related diseases that are triggered by ATP or nigericin, which may be risk factors for IDILI. [ABSTRACT FROM AUTHOR]
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- 2019
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32. A novel perspective on the preventive treatment of hydrazine compound-induced liver injury: Isoniazid liver injury as an example.
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Li, Xinyu, Li, Chengxian, Li, Chenyi, Wu, Chengzhao, Bai, Yuxuan, Zhao, Xu, Bai, Zhaofang, Zhang, Xigang, Xiao, Xiaohe, and Niu, Ming
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IN vitro studies , *EXPERIMENTAL design , *CANCER cell culture , *MEDICINAL plants , *IN vivo studies , *ANIMAL experimentation , *ANTI-inflammatory agents , *ISONIAZID , *LIVER diseases , *RATS , *GENE expression , *TUMOR necrosis factors , *PLANT extracts , *PHARMACEUTICAL chemistry , *ANIMALS - Abstract
Anethum graveolens L. (dill), which has been used as a medicine, spice and aromatic plant since ancient times, is not only a traditional Chinese medicines but also an important medicinal and functional food in Europe and Central and South Asia. In ethnomedicine, dill reportedly exerts a protective effect on the liver and has been widely used as a traditional medicine for the treatment of jaundice in the liver and spleen and inflammatory gout diseases in Saudi Arabia. Furthermore, studies have found that dill can regulate the NAT2 enzyme, and this plant was thus selected to study its alleviating effect on isoniazid liver injury. The purpose of this study was to explore the effect of dill on alleviating liver injury induced by hydrazine compounds represented by isoniazid through the use of network pharmacology combined with in vivo and in vitro experimental verifications. First, we screened the key targets of dill in the treatment of liver injury through the use of network pharmacology; we then performed GO and KEGG pathway enrichment analyses using the DAVID database. We also verified the alleviative and anti-inflammatory effects of dill on isoniazid liver injury in rats by animal experiments. We further investigated the modulating effect of dill on the enzymatic activity of NAT2, a common metabolizing enzyme of hydrazine compounds. A total of 111 key targets were screened through network pharmacology. In vivo experiments showed that dill reduced the amount of inflammatory factors produced by isoniazid, such as IL-10, IL-1β, TNF-α and IL-6, restored the levels of ALT, AST, r-GT, AKP and TBA in vivo, and attenuated isoniazid liver injury. Both in vivo and vitro results indicated that dill could regulate the expression of NAT2 enzymes. The results tentatively demonstrate that dill can alleviate isoniazid liver injury through multiple components, targets and pathways and exerts a regulatory effect on the NAT2 enzyme, and these findings thus provide new ideas for subsequent studies on hydrazide liver injury——reducing the risk of hydrazide-induced liver injury through anti-inflammation and regulation of NAT2 enzymes. [Display omitted] • Predicting potential targets and pathways of dill for the treatment of isoniazid liver injury. • Dill alleviated liver injury in rat. • Dill regulated inflammatory mediators levels in rat. • Dill improves cell survival in isoniazid-treated HepG2. • Dill regulates NAT2. [ABSTRACT FROM AUTHOR]
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- 2023
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33. Synthesis, crystal structure and biological properties of Cd and Zn coordination polymers based on a flexible tripodal ligand.
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Wang, Xia, Ling, Ning, Li, Hanbing, Xiao, Xiaohe, and Zhang, Yawen
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COORDINATION polymers , *CRYSTAL structure , *MORPHOLOGY , *METAL ions , *POLYMERS , *THERMAL stability - Abstract
Two new coordination polymers, namely poly[[hexathiocyanatotetrakis{μ3‐2,4,6‐trimethyl‐1,3,5‐tris[(triazol‐1‐yl)methyl]benzene}tricadmium(II)] 3.5‐hydrate], {[Cd3(SCN)6(C18H21N9)4]·3.5H2O}n (1), and poly[[hexathiocyanatotetrakis{μ3‐2,4,6‐trimethyl‐1,3,5‐tris[(triazol‐1‐yl)methyl]benzene}trizinc(II)] 3.5‐hydrate], {[Zn3(SCN)6(C18H21N9)4]·3.5H2O}n (2), have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR spectroscopy and single‐crystal X‐ray diffraction analysis. From the X‐ray analysis, it is noteworthy that polymers 1 and 2 are isostructural, with their three‐dimensional structures composed of three kinds of four‐connection metal ions and two kinds of three‐connection 2,4,6‐trimethyl‐1,3,5‐tris[(triazol‐1‐yl)methyl]benzene (TTTMB) ligand nodes. Each metal ion is six‐coordinated in a slightly distorted octahedral geometry. The antioxidant activity against DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) and the antidiabetic activity against α‐amylase of the synthesized compounds were evaluated in vitro. The results of the DPPH free‐radical scavenging assay showed that polymers 1 and 2 exhibited strong antioxidant effects, with IC50 values of 3.81 and 2.56 mg ml−1, respectively. The IC50 value in the antidiabetic studies of polymer 1 was 3.94 mg ml−1, while polymer 2 exhibited no antidiabetic activity. Polymers 1 and 2 revealed different inhibitory activities on DPPH and α‐amylase, which indicated that the metal ions play important roles in the biological activity of coordination polymers. In addition, the solid‐state photoluminescence properties and thermal stability of 1 and 2 have been investigated. [ABSTRACT FROM AUTHOR]
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- 2019
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34. Integrated Metabolomics and Network Pharmacology Study on Immunoregulation Mechanisms of Panax ginseng through Macrophages.
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Hao, Junjie, Hu, Huangwanyin, Liu, Jing, Wang, Xuan, Liu, Xiaoyi, Wang, Jiabo, Niu, Ming, Zhao, Yanling, and Xiao, Xiaohe
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BIOMARKERS , *CHOLINE , *ESCHERICHIA coli , *GINSENG , *GLUTATHIONE , *HIGH performance liquid chromatography , *MACROPHAGES , *MASS spectrometry , *METABOLISM , *PHAGOCYTOSIS , *PLANTS , *PHENOTYPES , *METABOLOMICS - Abstract
Panax ginseng (PG) is a widely used functional food and herbal with immunoregulation activity. Currently, immunoregulation studies of PG mainly focused on the specific actions of individual constituents. However, the integral immunoregulation mechanisms of PG need further research. In this study, an integrated metabolomics and network pharmacology approach were used to investigate it. High-content screening was used to evaluate macrophage phagocytosis activity of PG. Untargeted metabolomics profiling of murine macrophage cells with UHPLC-Q-TOF-MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Then, a macrophage phenotype related "ingredients-targets-metabolites" network of PG was constructed using network pharmacology for further research. As a result, PG can significantly enhance macrophage phagocytosis of GFP-E. coli. A total of twenty potential biomarkers and ten main pathways for which levels changed markedly upon treatment were identified, including glycerophospholipid metabolism, glutathione metabolism, choline metabolism, and taurine metabolism. Twenty compounds of PG associated with metabolomic changes were selected by the network pharmacology analysis, including ginsenoside Re, ginsenoside Rg1, frutinone A, and kaempferol. The network pharmacology results also showed that PG can polarize macrophages to both M1 and M2 phenotype but may be prone to M2 phenotype. In conclusion, our results indicated that PG may be prone to polarize macrophages to M2 phenotype by mainly regulating the glutathione and choline metabolism, which was related to twenty compounds of PG. [ABSTRACT FROM AUTHOR]
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- 2019
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35. Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication.
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Zhao, Jia, Xu, Guang, Hou, Xiaorong, Mu, Wenqing, Yang, Huijie, Shi, Wei, Wen, Jincai, Liu, Tingting, Wu, Zhixin, Bai, Jun, Zhang, Ping, Wang, Zhongxia, Xiao, Xiaohe, Zou, Wenjun, Bai, Zhaofang, and Zhan, Xiaoyan
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MEDICINAL plants , *ANIMAL experimentation , *HEPATITIS viruses , *ANTIVIRAL agents , *PRECIPITIN tests , *CELLULAR signal transduction , *IMMUNOBLOTTING , *INTERFERONS , *GENE expression , *ENZYME-linked immunosorbent assay , *FLUORESCENT antibody technique , *MEMBRANE proteins , *NUCLEOTIDYLTRANSFERASES , *POLYMERASE chain reaction , *CHINESE medicine , *MICE , *PHOSPHORYLATION , *PHARMACODYNAMICS - Abstract
Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or Yang Syndrome. Modern pharmacological studies have shown that Schisandra Chinensis regulates host immunity and exhibits anti-cancer, antiviral and liver-protecting effects. However, the specific mechanism by which Schisandra Chinensis modulates antiviral immunity is unknown. We sought to explore the therapeutic effect of the active components of Schisandra Chinensis on anti-viral immunity and further investigate the underlying mechanism. Immunoblotting, quantitative real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and immunoprecipitation were used to investigate the effect of schisandrin C (SC), one of the most abundant and biologically active components of Schisandra Chinensis , on the activation of cGAS-STING signaling pathway and the underlying mechanism. In addition, CMA-mediated STING activation and hydrodynamic injection-mediated HBV-replicating mouse model were used to investigate the effect of SC on the activation of STING signaling pathway and its antiviral effect in vivo. SC promoted cGAS-STING pathway activation, accompanied by increased production of interferon β (IFN β) and downstream gene expression. Moreover, SC also exerted anti-HBV effects, reducing HBeAg, HBcAg, HBsAg, and HBV DNA levels in hydrodynamic injection-mediated HBV-replicating mouse model and elevating the production of IFN β and expression of interferon-stimulated genes (IFIT1, ISG15, and CXCL10). Mechanistically, SC could facilitate the interaction between TANK-binding kinase 1 (TBK1) and STING, which is important for IRF3 phosphorylation and production of IFN β. Our study confirmed that SC enhances cGAS-STING pathway activation and inhibits HBV replication, as well as provides clues for chronic hepatitis B and other infectious diseases treated by SC. [Display omitted] • Schisandrin C (SC) promotes cGAS-STING pathway activation. • SC promotes cGAS-STING pathway activation by facilitating the interaction between TBK1 and STING. • SC markedly attenuates hepatitis B virus replication in vivo and promotes the expression of IFN β and ISGs. [ABSTRACT FROM AUTHOR]
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- 2023
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36. Flavonoids derived from licorice suppress LPS-induced acute lung injury in mice by inhibiting the cGAS-STING signaling pathway.
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Wen, Jincai, Qin, Shuanglin, Li, Yurong, Zhang, Ping, Zhan, Xiaoyan, Fang, Mingxia, Shi, Ce, Mu, Wenqing, Kan, Wen, Zhao, Jia, Hui, Siwen, Hou, Manting, Li, Hui, Xiao, Xiaohe, Xu, Guang, and Bai, Zhaofang
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TYPE I interferons , *LUNG injuries , *CELLULAR signal transduction , *FLAVONOIDS , *GENE expression , *VENOM , *SCORPION venom - Abstract
In recent years, we have found that the dysregulation of the cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING) pathway leads to the development of immune and inflammatory diseases, therefore, finding compounds that can specifically regulate this pathway is essential for effective regulation of the immune pathway for addressing inflammatory diseases. Licorice flavonoids (LFs), are active ingredients extracted from the Chinese herb licorice, which has been reported to have strong anti-inflammatory activity in previous studies. Here, we report that LFs inhibit the activation of the cGAS-STING pathway evidenced by the inhibition of the expression of type I interferons and related downstream genes such as interferon-stimulated gene 15 (ISG15) and C-X-C motif chemokine ligand 10 (CXCL10), as well as inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Notably, LFs markedly improve the LPS-induced acute lung injury by inhibiting the excessive activation of cGAS-STING signaling pathway. Mechanistically, LFs treatment leads to the blocking of 2′3′-cyclic GMP-AMP (cGAMP) synthesis resulting in an inhibition of the activation of the cGAS-STING pathway. Our results indicate that LFs is a specific inhibitor of the cGAS-STING pathway, which is suggested to be a potential candidate for the treatment of cGAS-STING pathway-mediated inflammatory diseases. [Display omitted] • Licorice flavonoids in licorice can specifically inhibit the cGAS-STING signaling pathway. • Licorice flavonoids inhibit the cGAS-STING pathway by reducing the synthesis of 2′3′-cGAMP. • Licorice flavonoids have ameliorative effects on acute lung injury in mice. [ABSTRACT FROM AUTHOR]
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- 2023
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37. Chinese herbal extract Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant hepatitis B virus (HBV) in vitro and effectively suppressed HBV replication in mouse model.
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Liu, Yan, Yao, Weiming, Si, Lanlan, Hou, Jun, Wang, Jiabo, Xu, Zhihui, Li, Weijie, Chen, Jianhong, Li, Ruisheng, Li, Penggao, Bo, Lvping, Xiao, Xiaohe, Lan, Jinchu, and Xu, Dongping
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HEPATITIS B virus , *VIRAL replication , *LABORATORY mice , *PLANT extracts , *DRUG resistance in microorganisms - Abstract
This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2.A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Su-duxing and entecavir combination showed a better anti-HBV effect than each single of agents. Mice treated with Su-duxing (45.0 mg kg −1 d −1 for 2 weeks) had 1.39 log 10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Quantitative RT-PCR verified that CCNA2 , ATF4 , FAS and CDKN1A expression levels had significant difference between Su-duxing-treated and control groups. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition. [ABSTRACT FROM AUTHOR]
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- 2018
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38. Liuweiwuling tablets attenuate BDL-induced hepatic fibrosis via modulation of TGF-β/Smad and NF-κB signaling pathways.
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Liu, Huimin, Dong, Fang, Li, Guangquan, Niu, Ming, Zhang, Congen, Han, Yanzhong, He, Lanzhi, Yin, Ping, Wang, Bin, Sang, Xiuxiu, Li, Ruishen, Wang, Jiabo, Bai, Zhaofang, and Xiao, Xiaohe
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LIVER disease prevention , *FIBROSIS , *ANIMAL experimentation , *CARRIER proteins , *CELLULAR signal transduction , *CHOLESTASIS , *COLCHICINE , *COLLAGEN , *FIBROBLASTS , *HERBAL medicine , *IMMUNOHISTOCHEMISTRY , *INTERLEUKINS , *CHINESE medicine , *PHOSPHORYLATION , *POLYMERASE chain reaction , *RATS , *TRANSFORMING growth factors-beta , *TUMOR necrosis factors , *WESTERN immunoblotting , *DNA-binding proteins , *REVERSE transcriptase polymerase chain reaction , *SIGNAL peptides , *DRUG administration , *DRUG dosage , *PREVENTION - Abstract
Ethnopharmacological relevance Liuweiwuling (LWWL) tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis with associated treatment regimens resulting in a concomitant reduction in transforming growth factor β1 (TGF-β1) levels in the serum of patients with hepatic fibrosis. TGF-β1 plays a prominent role in stimulating liver fibrogenesis and this effect is mediated by myofibroblasts (MFB) derived from hepatic stellate cells (HSCs). It is likely that this phenomenon underpins the antifibrotic effects associated with LWWL. Aim The purpose of this study was to investigate the antifibrotic effects and mechanisms pertaining to LWWL. Methods Hepatic fibrosis was induced in rats following bile duct ligation (BDL). Rats that underwent BDL received daily gavage administration of colchicine (0.2 mg/kg per day), LWWL (0.4, 1.6, 6.4 g/kg per day) or PBS (for the control group). Pathological changes in hepatic tissue were examined using hematoxylin and eosin (HE) and sirius red staining. Immunohistochemical analysis was performed to monitor α-SMA and type I collagen (Collagen I) protein expression. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analyses were used to monitor the expression of genes and proteins in the TGF-β/Smad signaling pathway, including TGF-β1, bone morphogenic protein and activin membrane-bound inhibitor (Bambi), Smad3, phosphorylated Smad3 (p-Smad3) and Smad7. We also monitored the expression of genes and proteins in the nuclear factor-κB (NF-κB) signaling pathway, including NF-κB p65, IκBα and phosphorylation of IκBα (p-IκBα), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β). Results LWWL dose-dependently inhibited BDL-induced liver injury and hepatic fibrosis in rats. Furthermore, LWWL reduced liver tissue collagen deposition, hydroxyproline content, liver dysfunction and α-SMA expression in BDL-induced hepatic fibrosis rats. Moreover, LWWL markedly prevented activation of the TGF-β/Smad signaling pathway by inhibiting expression of Smad2/3 and phosphorylation of Smad3, and upregulating the expression of Bambi and Smad7. In addition, LWWL regulated the expression of the inflammatory cytokines IL-1β, TNF-α and IL-6 by inhibiting the activation of NF-κB p65 and the phosphorylation of IκBα, and increasing the expression of IκBα. Conclusions LWWL can attenuate BDL-induced hepatic fibrosis in rats, and this effect may be due to modulation of the NF-κB-dependent inflammatory response and activation of HSC and TGF-β/Smad-mediated synthesis and degradation of Collagen I. [ABSTRACT FROM AUTHOR]
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- 2018
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39. Zingiberis rhizoma mediated enhancement of the pharmacological effect of aconiti lateralis radix praeparata against acute heart failure and the underlying biological mechanisms.
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Zhang, Lu, Lu, Xiaohua, Wang, Jiabo, Li, Pengyan, Li, Haotian, Wei, Shizhang, Zhou, Xuelin, Li, Kun, Wang, Lifu, Wang, Ruilin, Zhao, Yanling, and Xiao, Xiaohe
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HEART failure treatment , *GINGER , *RANUNCULACEAE , *CHINESE medicine , *ENERGY metabolism , *THERAPEUTICS - Abstract
Aconiti Lateralis Radix Praeparata (Fuzi), a type of Chinese materia medica, has been used to treat acute and chronic heart failure (HF) in traditional Chinese medicine and has been proven in numerous animal studies. It is also well-known that Zingiberis Rhizoma (Ganjiang) is ineffective in the treatment of HF, but it can enhance the anti-HF effect of Fuzi. However, the mechanism underlying this compatibility is still not well investigated. To investigate this mechanism, a model of acute heart failure (AHF) in SD rats induced by propafenone hydrochloride was established in this study. After oral treatments of Ganjiang, Fuzi or a combination of the two drugs in rats with AHF, heart function [e.g., heart rate (HR) and the maximal rising and declining rate of left ventricle pressure (±dp/dt max )] and serum indicators [e.g., brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and creatine kinase (CK)] were measured, and histopathological analysis of the heart was also performed. The biological mechanisms were further explored by measuring the protein expression level of the mitochondrial respiration chain complex (MRCC1-4) and the mRNA and protein expression levels of mitochondrial Ca 2+ uniporter (MCU) and its upstream proteins, mitochondrial Ca 2+ uniporter 1 and mitochondrial Ca 2+ uniporter 2 (MICU1-2). The expression levels of key enzymes downstream of the tricarboxylic acid cycle, including pyruvate dehydrogenase (PDH), malate dehydrogenase (MDH) and nicotinamide nucleotide transhydrogenase (NNT), were also measured. As a result, Ganjiang enhanced the therapeutic effect of Fuzi on AHF by raising the HR and ±dp/dt max ; decreasing the serum levels of BNP, LDH and CK; and alleviating histological damage of the myocardial tissue when compared to the treatments of Ganjiang or Fuzi alone. In conclusion, there was an enhancing effect of Ganjiang on the anti-AHF function of Fuzi treatment, and the potential mechanism of this effect may be related to the mitochondrial energy metabolism pathway mediated by MCU. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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40. The protective effects of compatibility of Aconiti Lateralis Radix Praeparata and Zingiberis Rhizoma on rats with heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α pathway.
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Lu, Xiaohua, Zhang, Lu, Li, Pengyan, Wang, Jiabo, Li, Ruisheng, Huang, Yinqiu, Wu, Mingquan, Zhou, Houqin, Li, Yang, Wei, Shizhang, Li, Kun, Li, Haotian, Zhou, Xuelin, Zhao, Yanling, and Xiao, Xiaohe
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HEART failure treatment , *PHYTOCHEMICALS , *BOTANICAL chemistry , *SIRTUINS , *DEACETYLASES - Abstract
Aconiti Lateralis Radix Praeparata (“Fuzi” in Chinese) in combination with Zingiberis Rhizoma (“Ganjiang” in Chinese) is commonly applied for the treatment of heart failure for thousands of years in China. However, its therapeutic mechanism is still poorly defined. This study aimed to investigate whether the compatibility of Fuzi and Ganjiang can protect rats with acute heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α signaling pathway. Hemodynamic parameters, including heart rate and left ventricular maximal rate of pressure rise and decline, were recorded in rats with acute heart failure induced by Propafenone hydrochloride. The serum levels of cardiac enzymes, including creatine kinase, lactate dehydrogenase, brain natriuretic peptide and cardiac troponin T, were also determined. The gene and protein levels of Sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and their downstream transcription factors were measured as well. The results indicated that Fuzi-Ganjiang herbal couple provided more significant benefits by restoring the left ventricular function and cardiac enzyme activities in comparison with their single use. Moreover, this herbal couple possessed a significant cardio-protection by increasing both gene and protein levels of Sirt1 and PGC-1α. In conclusion, the compatibility of Fuzi and Ganjiang had better therapeutic effect than their single use against failing heart, and the underlying mechanisms were partially through increasing mitochondrial biogenesis via Sirt1/PGC-1α pathway. [ABSTRACT FROM AUTHOR]
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- 2017
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41. Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury.
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He, Lanzhi, Yin, Ping, Meng, Yakun, Tang, Jinfa, He, Tingting, Niu, Ming, Guo, Yuming, Zhu, Yun, Jing, Jing, Li, Chunyu, Ma, Zhijie, Wang, Jiabo, Bai, Zhaofang, and Xiao, Xiaohe
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LIVER injuries , *STILBENE derivatives , *IDIOSYNCRATIC drug reactions - Published
- 2017
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42. Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats.
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Zhao, Yanling, He, Xuan, Ma, Xiao, Wen, Jianxia, Li, Pengyan, Wang, Jiabo, Li, Ruisheng, Zhu, Yun, Wei, Shizhang, Li, Haotian, Zhou, Xuelin, Li, Kun, Liu, Honghong, and Xiao, Xiaohe
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CHOLESTASIS , *ASPARTATE aminotransferase , *ALKALINE phosphatase , *HISTOPATHOLOGY , *NF-kappa B , *LABORATORY rats - Abstract
Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) −induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1β (IL-1β) and the hepatocyte transporters such as Na + /taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1β induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
43. Thermal activities of 6-gingerol, 8-gingerol and 6-shogaol on the potentiation of mitochondria thermogenesis based on microcalorimetry.
- Author
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Yang, Zhirui, Zhang, Dingkun, Zhang, Yaming, Wu, Mingquan, Liu, Honghong, Han, Xue, Zheng, Quanfu, Huang, Yinqiu, Chen, Chang, Zhang, Lu, Yan, Dan, Zhao, YanLing, and Xiao, Xiaohe
- Subjects
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SHOGAOL , *MITOCHONDRIA , *MICROCALORIMETRY , *HERBS , *BIOACTIVE compounds - Abstract
Zingiberis Rhizoma is a typical Chinese herb in 'hot' property. Nowadays, increasing attention has been aroused for its essential role in both health care and treatment of 'cold' syndrome. And research about characteristics of Zingiberis Rhizoma is able to provide an important reference for its deeper understand and successful clinic application. However, cognition level about the 'hot' property of Zingiberis Rhizoma is superficial, and mechanism behind the 'hot' presentation is still elusive and unclear. In this study, the 'hot' property of Zingiberis Rhizoma was investigated at a monomer level with assistance of microcalorimetry, an objective and sensitive method in evaluating biological activity. Three bioactive compounds including 6-gingerol, 8-gingerol and 6-shogaol were selected, and their thermal activities were explored with mitochondria as target. The power-time curves were recorded, and five thermal parameters ( k, P , T , Q and P ) were obtained. With PCA, P was calculated to be the main parameter to measure the bioactivities of 6-gingerol, 8-gingerol and 6-shogaol. Finally, the bioactivities of three subjects were compared with sequence to be 6-gingerol > 8-gingerol > 6-shogaol. Generally, our study is promising to offer a reference to the research about characteristics of Zingiberis Rhizoma or other herbs and is of great interest for clinic practice. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
44. Research Advances on Hepatotoxicity of Herbal Medicines in China.
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Liu, Changxiao, Fan, Huirong, Li, Yazhuo, and Xiao, Xiaohe
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LIVER disease diagnosis , *LIVER disease treatment , *HEPATOTOXICOLOGY , *ANIMALS , *DATABASES , *HERBAL medicine , *MEDICAL information storage & retrieval systems , *LIVER , *LIVER diseases , *MEDICAL screening , *MEDICINAL plants , *MINERALS , *RESEARCH , *TECHNOLOGY , *PHYTOCHEMICALS , *BIOINFORMATICS , *DIAGNOSIS , *THERAPEUTICS - Abstract
In general, herbal medicines have been considered as safe by the general public, since they are naturally occurring and have been applied in treatment for over thousands of years. As the use of herbal medicine is rapidly increasing globally, the potential toxicity of herbal drugs, in particular drug-induced liver injury (DILI), has now become a serious medical issue. According to the literature, the authors analyzed and discussed the hepatotoxicity problem of Chinese herbal medicines (CHM), including global overview on herbal-induced liver injury (HILI), current research progress on toxic CHM, diagnosis and treatment of HILI, and modern approaches and technologies of study of hepatotoxicity. As to promote the recognition of HILI and tackle the issue, a guideline for the diagnosis and treatment of HILI has recently been drafted by Chinese scientists. As suggested by the guideline, the hepatotoxicity issue of CHM, as a matter of fact, is overestimated. Up to date, the investigation of hepatotoxicity of CHM is now booming with worldwide application of CHM. This review therefore provides useful information for investigating hepatotoxicity of herbal medicine and characterizing DILI caused by CHM. In addition, authors describe in which way further efforts should be made to study the rationale of CHM and liver injury. [ABSTRACT FROM AUTHOR]
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- 2016
- Full Text
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45. Cold/hot pad differentiating assay of property differences of Mahuang and Maxingshigan decoctions.
- Author
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Zhao, Yanling, Jia, Lei, Wang, Jiabo, Zou, Wenjun, Yang, Hongbo, and Xiao, Xiaohe
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THERAPEUTIC use of ephedra , *BIOLOGICAL assay , *CHINESE medicine , *OXYGEN consumption , *ENERGY metabolism , *ADENOSINE triphosphatase , *SEASONAL temperature variations - Abstract
Context: Chinese medicines with different cold/hot properties have various pharmacological actions on multiple organisms. Objective: The objective of this study was to explore the cold/hot property differences of traditional Chinese medicine formulas of Mahuang and Maxingshigan decoctions. Materials and methods: A novel cold/hot pad differentiating assay method based on the Intelligent Animal Temperature Tropism Behavior monitoring system at 20 °C (cold pad) and 30 °C (hot pad) was introduced to investigate the variability of temperature tropism among the mice treated by 0.4 mL/20 g (drug volume/body weight) of Mahuang decoction and Maxingshigan decoction, respectively. Meanwhile, the oxygen consumption and activities of adenosine triphosphatase (ATPase) were measured to explore the energy metabolism mechanism. Results: Results showed that the differences between cold/hot properties of Mahuang decoction and Maxingshigan decoction were significant (p < 0.05). Mahuang decoction produced significant synergic effect (a combination index of 1.60), while Maxingshigan decoction expressed significant antagonistic effect (a combination index of 0.35). The changes of energy metabolism including ATPase activity and oxygen consumption might be the possible factors to result in the differences. Those influences tended to be coherent with the definition of cold/hot properties of Chinese medicines based on traditional Chinese medicinal theory. Conclusions: The results indicated that the method based on cold/hot pad differentiating array could objectively and quantitatively represent the cold/hot properties of different compatibilities of traditional Chinese medicines in an ethological way according to the changes of animal’s temperature tropism. These findings would provide some experimental basis and data references as well as a novel evaluation method for the study of the regularity of recipe composition. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
46. Microcalorimetry and turbidimetry to investigate the anti-bacterial activities of five fractions from the leaves of Dracontomelon dao on P. aeruginosa.
- Author
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Wu, Mingquan, Qu, Fen, Zhao, Yanling, Wang, Jiabo, Su, Haibin, Chen, Chang, Zhang, Chenglong, Guo, Yanlei, Zhang, Ping, Ma, Xiao, Yang, Zhirui, Zhang, Yaming, and Xiao, Xiaohe
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MICROCALORIMETRY , *TURBIDIMETRY , *ANTIBACTERIAL agents , *COMPOSITION of leaves , *PSEUDOMONAS aeruginosa - Abstract
As a healthcare-associated pathogen with the resistance to anti-bacterial agent, P. aeruginosa has caused prevalent public burden and should not be ignored. Facing the realistic situation, developing novel anti- P. aeruginosa agents is urgent. Leaves of Dracontomelon dao were extensively used in southern China to treat various infectious diseases 1000 years ago. And in the study, the heat flow power-time (HFP-time) curves generated by P. aeruginosa which were disturbed by the five fractions (PE, CHCl, EtOAc, n-BuOH and Vestiges fraction) from them were investigated through microcalorimetry, and then, some thermal kinetic parameters were obtained from the curves to characterize the metabolism of P. aeruginosa. The parameters were analyzed by principal component analysis (PCA), and the anti- P. aeruginosa activities of the five fractions were systematically compared and evaluated. The results showed that five fractions all expressed respective anti- P. aeruginosa effects in a dose-dependent manner and especially the performance of EtOAc fraction with half-inhibitory concentration (IC50) of 18.06 μg mL. Simultaneously, the prospective performance of EtOAc fraction was confirmed by turbidimetry. Based on the promising anti- P. aeruginosa activities of EtOAc fraction, it could be developed as a novel anti-bacterial agent used in practice for treating certain infectious diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
47. Biological fingerprinting based on microcalorimetry.
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Zhang, Yaming, Wang, Jiabo, Zhao, Yanling, Wang, Ruilin, Niu, Ming, Shen, Honghui, Bai, Zhaofang, Guo, Yuming, Wang, Zhongxia, and Xiao, Xiaohe
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HUMAN fingerprints , *MICROCALORIMETRY , *CHINESE medicine , *TRADITIONAL medicine , *HERBAL medicine - Abstract
Traditional Chinese medicine (TCM) injections have been used as valuable preparations of herbal medicines. However, minor quality variation of TCM injections in the storage and transportation often results in adverse drug reactions and adverse drug events. In this study, biothermal dynamic test combined with chemical analysis was applied to monitor the consistency and stability of TCM injections. Shuang- huang- lian freeze-dried powder for injection (SHLPI) was selected as a representative herbal injection. Ten batches of normal samples and nine batches of artificially abnormal samples were collected. High-performance liquid chromatography (HPLC) fingerprinting was frequently used to characterize the chemical composition of TCM injections. However, it could not monitor minor quality fluctuation of the samples under special conditions such as lighting, high temperature, and bacterial contamination. The biological activity of SHLPI on the growth of Staphylococcus aureus was detected and then analyzed with chemometric methods including similarity evaluation and partial least-squared discriminant analysis. The similarity of abnormal samples in HPLC fingerprinting was > 0.99, whereas most of the abnormal samples in biological fingerprinting was 0.943-0.652, demonstrating the greater discriminating ability of biological fingerprinting. Our study demonstrated that biological fingerprinting is effective to monitor the quality fluctuation of TCM injections and could improve the quality control of herbal medicines. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
48. Antibacterial effect of different extracts from Wikstroemia indica on Escherichia coli based on microcalorimetry coupled with agar dilution method.
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Chen, Chang, Qu, Fen, Wang, Jian, Xia, Xinhua, Wang, Jiabo, Chen, Zhe, Ma, Xiao, Wei, Shizhang, Zhang, Yaming, Li, Jianyu, Gong, Man, Wang, Ruilin, Liu, Honghong, Yang, Zhirui, Li, Yonggang, Zhao, Yanling, and Xiao, Xiaohe
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ANTIBACTERIAL agents , *EXTRACTION (Chemistry) , *WIKSTROEMIA , *ESCHERICHIA coli , *BIOCHEMISTRY - Abstract
The root of Wikstroemia indica has been widely used in China as folk medicine for the treatment for arthritis, whooping cough, cancer, and bacillosis. However, the constituents which have antibacterial activity were not clarified yet. In this study, the antibacterial effect of five extracts from W. indica on Escherichia coli was evaluated by microcalorimetry coupled with agar dilution method. The ethanol extract of W. indica was isolated with organic solvents of different polarities including petroleum (P.E.) extract, chloroform (CHCl) extract, ethyl acetate (EtOAc) extract, n-butylalcohol (nBuOH) extract, and residue extract. The metabolic profiles of E. coli growth at 37 °C were measured by microcalorimetry. According to the principal component analysis, k, k, and P were obtained from heat flow power-time (HFP-time) curve. The agar dilution method was performed to verify the results of thermodynamics. The results of microcalorimetric experiment indicated that EtOAc fraction demonstrated the strongest antibacterial activity with half-inhibitory concentration of 92.4 μg mL. Meanwhile, similar results were gained from the common method of agar diffusion, which suggested that EtOAc extract could be further developed as antibacterial bioactive fraction of W. indica. Altogether, microcalorimetry is a useful technique to provide sufficient quantitative information and evaluate the antimicrobial effect with its sensitive. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
49. Kushenin Combined with Nucleos(t)ide Analogues for Chronic Hepatitis B: A Systematic Review and Meta-Analysis.
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Chen, Zhe, Ma, Xiao, Zhao, Yanling, Wang, Jiabo, Zhang, Yaming, Zhu, Yun, Wang, Lifu, Chen, Chang, Wei, Shizhang, Yang, Zhirui, Gong, Man, Shen, Honghui, Bai, Zhaofang, Guo, Yuming, Niu, Ming, and Xiao, Xiaohe
- Subjects
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ANTIVIRAL agents , *CHINESE medicine , *ASPARTATE aminotransferase , *COMBINATION drug therapy , *CHI-squared test , *CONFIDENCE intervals , *HERBAL medicine , *MEDICAL databases , *INFORMATION storage & retrieval systems , *MEDICAL information storage & retrieval systems , *MEDLINE , *META-analysis , *ONLINE information services , *RESEARCH funding , *VIRAL antigens , *SYSTEMATIC reviews , *ALANINE aminotransferase , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *RESEARCH bias , *SEROCONVERSION , *DATA analysis software , *CHRONIC hepatitis B , *ODDS ratio - Abstract
Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB). Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software. Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency. Conclusion. KS combined with NAs improves the efficacy of NAs in CHB. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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50. Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway.
- Author
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Cao, Bo, Wang, Shiyuan, Li, Ruisheng, Wang, Zhihong, Li, Taifeng, Zhang, Yuanyuan, Dong, Bin, Li, Yingying, Lin, Mengmeng, Li, Xingjie, Xiao, Xiaohe, Li, Chunyu, and Li, Guohui
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GUT microbiome , *ANTINEOPLASTIC agents , *NEOVASCULARIZATION , *CHINESE medicine , *LUNG cancer - Abstract
Lung cancer poses a serious threat to human health. Although targeted therapies have led to breakthroughs in the treatment of lung cancer, drug resistance and side effects limit their clinical applications. Xihuang pill (XHW), a classical anti-cancer traditional Chinese medicine formula, has been clinically proven to be an effective complementary therapy in the treatment of various of cancers. However, the underlying mechanism for its use in combination with anti-cancer drugs remains unclear. Here, we explored the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung cancer (LLC). We used gut microbiota and transcriptomics to elucidate the regulatory properties of XHW in improving anti-lung cancer effect of anlotinib. The results showed that combination treatment of XHW with Anlotinib significantly inhibited tumor growth in LLC-bearing mice. We found that XHW played a key role in the regulation of gut microbiota using 16 s rRNA sequencing analysis. Specifically, XHW increased the proportion of the beneficial bacteria Bacteroides and g_norank_f_Muribaculaceae. Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients. [Display omitted] • XHW improved the effects of anlotinib in the Lewis lung cancer (LLC) -incubated mouse model. • XWH enhances the antitumor effect of Anlotinib by modulating gut microbiota composition. • XHW potentiates the antitumor effect of Anlotinib by regulating tumor angiogenesis. • Combination therapy with XHW and Anlotinib offers a new therapeutic strategy for lung cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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