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Background: The study was designed to systematically evaluate the efficacy and safety of Fuzheng-Buyi formula in treating castration-resistant prostate cancer (CRPC)., Methods: A computer-based search were conducted in the databases, including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, and the Cochrane database to identify all randomized controlled trials. The studies investigating the efficacy and safety of Fuzheng-Buyi formula combined with Western medicine for the treatment of CRPC were included from January 1st, 2010 to December 31st, 2023. The quality of the included studies was evaluated according to the Cochrane Handbook manual, and meta-analysis was performed using Review Manager 5.3 and R Studio 4.2.3 software., Results: In this study, a total of 18 trials were included, encompassing a population of 1093 patients diagnosed with CRPC. The results of the meta-analysis showed that the combination of Fuzheng-Buyi formula and Western drugs was more effective in increasing the overall efficacy rate (risk ratio = 1.31, 95% confidence interval [CI] [1.17, 1.46], P < .00001), decreasing Traditional Chinese Medicine syndrome score (mean difference [MD] = -4.40, 95% CI [-6.10, -2.70], P < .00001), and quality of life scale (physiological condition MD = -2.31, 95% CI [-3.13, -1.48], P < .00001; social well-being MD = 1.26, 95% CI [0. 59, 1.94], P = .0002; emotional well-being MD = -2.04, 95% CI [-2.96, -1.12], P < .00001; functional well-being MD = -3.18, 95% CI [2.11, 4.26], P < .00001; others should be paid to MD = -3.15, 95% CI [-4.93, -1.37], P = .0005) compared with the Western medicine alone. And the incidence of adverse events was significantly lower in the combination treatment group compared with Western medicine group (risk ratio = 0.58, 95% CI [0.46, 0.73], P < .00001)., Conclusion: The combination of Fuzheng-Buyi formula and Western medicine was more effective in improving the clinical efficacy and quality of life of CRPC patients, with lower incidence of adverse events compared with Western medicine alone., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sanhua Decoction (SHD) is a classic prescription for the treatment of stroke in the clinic. Based on the combination strategy in vitro and in vivo, the chemical constituents of SHD were characterized by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, and the metabolites of five effective anthraquinone aglycones (emodin, chrysophanol, rhein, aloe-emodin, and physcion) of rhubarb in SHD were studied. A total of 222 compounds were isolated and identified in vitro, including 50 flavonoids and their glycosides, 41 coumarins, 22 anthraquinones, 22 tannins, 14 phenylpropanoids, 16 alkaloids, 18 organic acids and their esters, 14 lignans, six anthrones, and 19 other compounds. A total of 111 prototype components were isolated and identified in vivo. Among them, 26, 82, 101, and 46 prototype components and 87 metabolites were detected in plasma, urine, feces, and bile for the first time. This study provides a basis for the identification of chemical components in vivo and in vitro and the analysis of potential pharmacodynamic components of SHD, and provides a basis for further study of pharmacodynamic mechanism., (© 2024 Wiley‐VCH GmbH.)

Xinglou Chengqi decoction (XLCQD) is a Chinese formula that offers benefits in ischemic stroke. However, the underlying mechanism of the effects of XLCQD-mediated anti-ischemic stroke effects remains obscure. This study investigates the ferroptosis mechanism of XLCQD against cerebral ischemia/reperfusion (I/R) injury using rat models of middle cerebral artery occlusion/reperfusion (MCAO/R). Ferroptosis differs from traditional cell death pathways and is linked to oxidative stress-induced lipid peroxidation and glutathione (GSH) depletion, which is essential to the development of ischemic stroke. In this study, it is shown that XLCQD improves brain infarction, neurological dysfunction, and histopathological changes caused by MCAO/R exposure, and improving I/R-induced oxidative damage through inhibition of ferroptosis via (Solute Carrier Family 7 Member 11) SLC7A11/ (glutathione peroxidase 4) GPX4 pathway. Interestingly, it is found that XLCQD-mediated protection in I/R is reversed by the silence of SLC7A11. XLCQD intervention significantly promotes GSH content and suppresses Reactive Oxygen Species(ROS), iron accumulation, as well as Malondialdehyde (MDA) generation, are markedly abrogated when SLC7A11 is knockdown by SLC7A11-shRNA transfection, indicating that SLC7A11 is the main target of XLCQD to further trigger intracellular events. In conclusion, XLCQD attenuates in vivo cerebral I/R injury by reducing ferroptosis via the SLC7A11/GPX4 pathway., (© 2024 Wiley‐VCH GmbH.)

We used network pharmacology, molecular docking, and in vitro experiments to explore the mechanisms of Astragali Radix in the treatment of lupus nephritis. We screened compounds and targets of Astragali Radix, as well as related genes of lupus nephritis from databases. We identified 211 common genes and 44 compounds between the herb and the disease, and constructed global, narrowed, hierarchical Compound-Target Interaction networks to illustrate the possible mechanism. We found that the PI3K/AKT/mTOR pathway is a core target gene set identified through enrichment analysis, PPI analysis and MCODE analysis. In vitro experiments showed that freeze-dried Astragali powder inhibits activation of PI3K, AKT1 and mTOR in TGF-β1 stimulated HK-2 cells. Molecular docking demonstrated that (R)-isomucronulatol, 3,9,10-trimethoxypterocarpan and astrapterocarpan exhibited promising binding affinity to PI3K, AKT, and mTOR proteins., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, largely due to the limitations of available therapeutic strategies. The traditional Chinese medicine Qizhu Anticancer Prescription (QZACP) can improve the quality of life and prolong the survival time of patients with HCC. However, the precise mechanisms underlying the anti-cancer properties of QZACP remain unclear., Purpose: This study examined the anti-hepatocarcinogenic properties of QZACP, with a specific focus on its influence on the p21-activated secretory phenotype (PASP)-mediated immune surveillance, to elucidate the underlying molecular pathways involved in HCC., Materials and Methods: Cell proliferation was measured using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and clonogenic assays. The cell cycle was evaluated using flow cytometry, and senescence was identified by staining with senescence-associated beta-galactosidase (SA-β-gal). A primary liver cancer model produced by diethylnitrosamine was established in C57 BL/6 mice to assess the tumor-inhibitory effect of QZACP. The liver's pathological characteristics were examined using hematoxylin and eosin staining. PASP screening was performed using GeneCards, DisGeNet, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas databases. Western blot analysis, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and Transwell migration assays were performed., Results: Serum containing QZACP enhanced p21 expression, triggered cell cycle arrest, accelerated cell senescence, and suppressed cell proliferation in Huh7 and MHCC-97H liver cancer cells. QZACP reduced the quantity and dimensions of liver tumor nodules and enhanced p21 protein expression, SA-β-Gal staining in tumor lesions, and cytotoxic CD8 + T cell infiltration. Bioinformatic analyses indicated that PASP factors, including hepatocyte growth factor, decorin (DCN), dermatopontin, C-X-C motif chemokine ligand 14 (CXCL14), and Wnt family member 2 (WNT2), play an important role in the development of HCC. In addition, these factors are associated with the presence of natural killer cells and CD8 + T cells within tumors. Western blotting and ELISA confirmed that QZACP increased DCN, CXCL14, and WNT2 levels in tumor tissues and peripheral blood., Conclusions: QZACP's suppression of HCC progression may involve cell senescence mediated via p21 upregulation, DCN, CXCL14, and WNT2 secretion, and reversal of the immunosuppressive microenvironment. This study provides insights that can be used in the development of new treatment strategies for HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of β cells., Aim of the Study: We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used., Materials and Methods: The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 μg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining., Result: 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic β-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKβ/AMPK pathway., Conclusions: The present study findings show that JTTF may protects β-cells by inhibiting the CaMKKβ/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Irinotecan (CPT-11) is a commonly prescribed chemotherapeutic for the treatment of colon cancer. Unfortunately, acute and delayed diarrhea are prominent side effects of CPT-11 use, and this limits its therapeutic potential. The curative effect of Huangqin decoction (HQD) on chemotherapy-induced diarrhea has been proven. This study investigated the efficacy of the components of HQD (baicalein, baicalin, and paeoniflorin) on CPT-11-induced diarrhea and their underlying mechanisms. Baicalein was found to be the most effective component in improving CPT-11-induced enterotoxicity by intestinal permeability test, ELISA, fluorescence co-localization, and IHC. The combination of baicalin, baicalin and paeoniflorin can obtain similar therapeutic effect to that of HQD. Mendelian randomization analysis, 16 s rRNA sequencing, and fluorescence imaging revealed that baicalein and baicalin significantly inhibited β-glucuronidase (β-GUS) activity. Bacterial abundance analysis and scanning electron microscopy showed that baicalein inhibited the proliferation of Escherichia coli by destroying its cell wall. The molecular dynamics and site-directed mutagenesis results revealed the structural basis for the inhibition of β-GUS by baicalein and baicalin. The results above provide a new idea for the development of drug therapy for adjuvant chemotherapy and theoretical guidance for the optimization of molecular structure targeting β-GUS., (© 2024. The Author(s).)

Zuojin Pill (ZJP), a traditional Chinese medicine prescription composed of Rhizoma Coptidis and Euodiae Fructus in the ratio of 6:1 (w/w), has been widely used for the treatment of gastric disorders. However, an in-depth understanding of in vivo metabolism and distribution profiles of protoberberine alkaloids (PBAs) and indole alkaloids (IDAs) in ZJP is lacking. In this study, a method using ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was developed to systematically screen the alkaloids and their metabolites in rat plasma and various tissues after oral administration of ZJP. Furthermore, bioinformatics and molecular docking analyses were conducted to elucidate the contribution of the alkaloids and metabolites enriched in the stomach to the therapeutic effect of ZJP on gastritis. A total of 33 compounds, including 7 prototype alkaloids and 26 metabolites, were chemically defined or tentatively identified in this work. The metabolic pathways of PBAs (hydroxylation, oxidation, reduction, demethylation, demethylenation, glucuronide conjugation, sulfate conjugation) and IDAs (hydroxylation, glucuronide conjugation) were revealed. Notably, 7 prototype alkaloids and 18 metabolites were detected in the stomach, indicating their propensity for gastric distribution. These alkaloids and metabolites showed strong affinities with the 7 hub targets associated with gastritis, such as CCR7, CXCR4, IL6, IFNG, CCL2, TNF, and PTPRC, and could be considered the potential active substances of ZJP for treating gastritis. In conclusion, this study clarified the gastric distribution propensity of PBAs and IDAs and their metabolites, as well as their favorable binding interactions with gastritis-related targets, which could provide essential data for the further study of the pharmacodynamic material basis and gastroprotective mechanism of ZJP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Codonopsis Radix, commonly known as Dangshen in Chinese, is frequently used to treat deficiencies of spleen and lung Qi, gastrointestinal discomfort, fatigue, asthmatic breathing, sallow complexion, lack of strength, shortness of breath, deficiencies of both Qi and blood, as well as impairments to both Qi and body fluids in suboptimal health status., Aim of the Review: This review systematically expounds on the modern pharmacological studies related to the use of Codonopsis Radix in invigorating Qi and nourishing the body in recent years. The aim is to provide theoretical research and reference for the in-depth and systematic exploration and development of the applications of Codonopsis Radix in the fields of food and medicine., Materials and Methods: This study employs "Codonopsis Radix," "Codonopsis," and "Dangshen" as keywords to gather pertinent information on Codonopsis Radix medicine through electronic searches of classical literature and databases such as PubMed, Elsevier, Google Scholar, Wiley, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Baidu Scholar., Results: From previous studies, activities such as immune system modulation, gastrointestinal motility regulation, cardiac function revitalization, lung function improvement, blood circulation enhancement, aging process deceleration, learning and memory augmentation, fatigue resistance enhancement, and liver and kidney damage protection of Codonopsis Radix have been reported. Recognized as an important medicine and food homologous traditional Chinese herbal remedy for supplementing deficiencies, its mode of action is multi-elemental, multi-systemic, multi-organ, multi-mechanistic, and multi-targeted. Furthermore, the benefits of its tonic surpass its therapeutic value, establishing it as an extraordinary preventive and therapeutic medicine., Conclusions: With its long history of traditional applications and the revelations of contemporary pharmacological research, Codonopsis Radix exhibits great potential as both a therapeutic agent and a dietary supplement for further research in medicine, nutrition, and healthcare., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism., Methods: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model., Results: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids., Conclusion: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could be perceived to have influenced the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Myocardial infarction (MI) is a significant threat to human health and life. Xue-Fu-Zhu-Yu Decoction (XFZYD), a renowned traditional Chinese medicine prescription for treating myocardial infarction, is known to play a significant role in the management of MI. However, its mechanism of action remains unclear. Through network pharmacology analysis of compound-target interactions, we have identified Carbonic Anhydrase II (CA2) as a critical target for XFZYD in the treatment of MI. Subsequently, we will embark on a target-based drug design approach with a focus on CA2 as the key target: Pharmacophore modeling: Two pharmacophore models were developed and validated to screen for small molecules with CA2 inhibitory features. Virtual screening: Based on two pharmacophore models, small molecules with the property of binding to the CA2 target were screened from a virtual screening library. Molecular docking: Molecular docking was employed to identify small molecules with stable binding affinity to CA2. ADMET prediction: ADMET models were utilized to screen for small molecules with favorable pharmacological properties. Molecular dynamics: Molecular dynamics simulations were further conducted to analyze the binding modes of the selected small molecules with CA2, ultimately resulting in the identification of Ligand 3 and Ligand 5 as small molecule inhibitors targeting CA2. Finally, the mechanisms underlying the anti-MI effects were discussed. The primary objective of this article is to uncover the mechanism by which XFZYD acts on MI and utilize it for drug development. These findings provide novel avenues for the development of anti-MI drugs.Communicated by Ramaswamy H. Sarma.

Rational: Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products., Methods: An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products., Results: A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected., Conclusion: The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine., (© 2024 John Wiley & Sons Ltd.)

Chinese Herbal Medicine (CHM) is being more and more used in cancer treatment because of its ability to regulate the immune system. Chinese Herbal Medicine has several advantages over other treatment options, including being multi-component, multi-target, and having fewer side effects. Dendritic cells (DCs) are specialized antigen presenting cells that play a vital part in connecting the innate and adaptive immune systems. They are also important in immunotherapy. Recent evidence suggests that Chinese Herbal Medicine and its components can positively impact the immune response by targeting key functions of dendritic cells. In this review, we have summarized the influences of Chinese Herbal Medicine on the immunobiological feature of dendritic cells, emphasized an anti-tumor effect of CHM-treated DCs, and also pointed out deficiencies in the regulation of DC function by Chinese Herbal Medicine and outlined future research directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shen, Li, Wang, Xiang and Xie.)

Ethnopharmacological Relevance: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear., Aim of This Study: To elucidate the underlying endotype mechanisms of DHI in the CTBH., Materials and Methods: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22., Results: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments., Conclusions: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) is one of the leading causes of death worldwide, and its internal medicine treatments are mostly single/few-target chemical drugs. Long-term use of cardiovascular drugs for complex chronic diseases may lead to serious adverse drug reactions. Traditional Chinese medicine (TCM) has been used to treat heart diseases for thousands of years, helping to ease symptoms and prolong patients' lifespan in ancient China. TCM has the pharmacological characteristics of being multi-component, multi-target and multi-pathway, and the combined application of TCM and western medicine can be an alternative treatment for chronic and intractable diseases with high safety levels. This article reviewed the interactions and synergistic effect of TCM and cardiovascular drugs. In the treatment of arrhythmia, TCM combined with western medicine can more effectively regulate patients' cardiac electrophysiological characteristics, reduce the onsets of premature beat and heart rate variability, lower the levels of QT interval dispersion and serum inflammatory factors, alleviate clinical symptoms and TCM syndromes, and improve cardiac function with good safety levels. In the treatment of hypertension, integrative medicine can more steadily reduce blood pressure and levels of serum inflammatory factors and improve hemodynamic indexes and exercise tolerance, and it has high safety levels, especially for pregnant women. As for coronary heart disease, the combination of TCM and antiplatelet drugs may promote the absorption of each other. However, the interaction risk of pharmacokinetic mechanism between them is low at the dose of efficacy. Integrative medicine can reduce the level of N-terminal pro-brain natriuretic peptide, delay cardiac remodeling and improve heart function and quality of life for patients with heart failure with high safety levels., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Coptidis Rhizoma (CR) holds significant clinical importance. In this study, we conducted a comparative analysis of CR's dispensing granule decoction (DGD) and traditional decoction (TD) to establish a comprehensive evaluation method for the quality of DGD. We selected nine batches of DGD (three from each of manufacturers A, B and C) and 10 batches of decoction pieces for analysis. We determined the content of representative components using high-performance liquid chromatography and assessed the content of blood components in vivo post-administration using ultra-performance liquid chromatography-mass spectrometry. The antibacterial activity was measured using the drug-sensitive tablet method. To evaluate the overall consistency of DGD and TD, we employed the CRITIC method and Grey relational analysis method. Our CRITIC results indicated no significant difference between the CRITIC scores of DGD-B and TD, with DGD-B exhibiting the highest consistency and overall quality. However, DGD-A and DGD-C showed variations in CRITIC scores compared with TD. After equivalent correction, the quality of DGD-A and DGD-C approached that of TD. Furthermore, our Grey relational analysis results supported the findings of the CRITIC method. This study offers a novel approach to evaluate the consistency between DGD and TD, providing insights into improving the quality of DGD., (© 2024 John Wiley & Sons Ltd.)

Background: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet β cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota., Purpose: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the "intestinal flora bile acid TGR5'' axis., Methods: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum., Results: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion., Conclusion: GQD can regulate the "intestinal flora-bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Ethnopharmacological Relevance: Pseudobulbus Cremastrae seu Pleiones (PCSP) is a multi-source traditional Chinese medicine (TCM) with diverse chemical compositions and toxicity levels. The authenticity identification and safety evaluation of PCSP have attracted widespread attention in clinical applications., Aim of This Study: The objective of this study was to evaluate the authenticity and safety of commercially available PCSP., Materials and Methods: Morphological and microscopic identification, HPLC chromatogram, UPLC-Q-TOF-MS/MS with molecular networking were applied to the authenticity identification of PCSP. The safety of different PCSPs was evaluated by acute toxicity in zebrafish at maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC 10 ). Intestinal toxicity of PCSP was assessed through histological staining, intestinal goblet cells, neutrophils, and intestinal opacity., Results: Four sources of PCSP varied in size, epidermal longitudinal grooves, and microscopic features. GNPS analysis identified 61, 47, 44, and 56 chemical compounds in Cremastra appendiculate (CA), Oreorchis patens (Lindl.) Lindl. (OPL), Iphigenia indica A. Gray (IIG), and Tulipa edulis (Miq.) Baker (TEB). Colchicine and militarine, were discovered as distinguishing markers. Acute toxicity in zebrafish ranked as follows: IIG > OPL > CA > TEB. Further studies on the intestinal toxicity of the authentic PCSP (CA, OPL) showed that CA induced less damage with a smaller lumen area, fewer neutrophils and goblet cells, and reduced peristalsis inhibition compared to OPL, indicating greater safety., Conclusion: Four different sources of PCSP were accurately distinguished based on three dimensions: character, components, and toxicity. OPL and CA were considered as genuine products, while CA with lower toxicity was more suitable for clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Current treatment options for cholestatic liver diseases are limited, and addressing impaired intestinal barrier has emerged as a promising therapeutic approach. Si-Ni-San (SNS) is a Traditional Chinese Medicine (TCM) formula commonly utilized in the management of chronic liver diseases. Our previous studies have indicated that SNS effectively enhanced intestinal barrier function through the modulation of gut microbiota., Aim of the Study: This study aims to verify the therapeutic effects of SNS on cholestatic liver injury, focusing on elucidating the underlying mechanism involving the gut-liver axis., Materials and Methods: The 16s RNA gene sequencing, non-targeted metabolomics were used to investigate the effects of SNS on the gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) was conducted to identify potential beneficial probiotics underlying the therapeutic effects of SNS., Results: Our results demonstrated that SNS significantly ameliorated cholestatic liver injury induced by partial bile duct ligation (pBDL). Additionally, SNS effectively suppressed cholestasis-induced inflammation and barrier dysfunction in both the small intestine and colon. While SNS did not impact the intestinal FXR-FGF15-hepatic CYP7A1 axis, it notably improved gut microbiota dysbiosis and modulated the profile of microbial metabolites, including beneficial secondary bile acids and tryptophan derivatives. Furthermore, gut microbiota depletion experiments and FMT confirmed that the therapeutic benefits of SNS in cholestatic liver disease are dependent on gut microbiota modulation, particularly through the promotion of the growth of potential probiotic P. goldsteinii. Moreover, a synergistic improvement in cholestatic liver injury was observed with the co-administration of P. goldsteinii and SNS., Conclusion: Our study underscores that SNS effectively alleviates cholestatic liver injury by addressing gut microbiota dysbiosis and enhancing intestinal barrier function, supporting its rational clinical utilization. Furthermore, we highlight P. goldsteinii as a promising probiotic candidate for the management of cholestatic liver diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cis-trans isomers of N-isobutyl-2E,4E,8Z,10E-dodecatetraenamide (DDA-E) and N-isobutyl-2E,4E,8Z,10Z-dodecatetraenamide (DDA-Z) are representative alkamides with numbness of tongue, anti-inflammatory and analgesic activities of Asari Radix et Rhizoma. However, their respective metabolic pathways and pharmacokinetic behaviors are still unknown. This study aim to investigate the metabolism of the two alkamides in vitro and in vivo using ultra-high-performance liquid chromatography-quadruple-time-of-flight mass spectrometry. Furthermore, a rapid, sensitive, and selective ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to quantify DDA-E/Z in rat plasma. Results indicated that DDA-E and DDA-Z showed significant differences in metabolism and pharmacokinetics. Across all samples, 24 metabolites of DDA-E and 21 metabolites of DDA-Z were detected. A variety of pathways were involved in the production of these metabolites, mainly hydroxylation and oxidation. The linear range of DDA-E/Z was 1-2500 ng/mL (R 2 = 0.9984), and the lowest quantification limit was 1 ng/mL. Precision, accuracy, extraction recovery, matrix effect, and stability of DDA-E/Z were within acceptable limits. Pharmacokinetic research was conducted using male Sprague-Dawley rats receiving intravenous (1 mg/kg) or intragastric (40 mg/kg) administration of DDA-E or DDA-Z solution. There was a calculated absolute bioavailability of 15.67 % for DDA-E and 4.83 % for DDA-Z when consumed orally. The apparent volume of distribution of intravenous and intragastric administrations were 4.44 ± 0.41 L/kg and 5.18 ± 0.67 L/kg for DDA-E, and 1.56 ± 1.66 L/kg and 2.35 ± 0.42 L/kg for DDA-Z. The maximal plasma concentrations of DDA-E and DDA-Z were 599.84 ± 149.92 nM and 422.09 ± 69.17 nM, and the time to maximum peak were 4.33 ± 3.51 h and 0.70 ± 1.12 h, respectively. In conclusion, in subsequent pharmacodynamics and safety evaluation studies, great attention should be paid to the metabolic characteristics and pharmacokinetic differences between DDA-E and DDA-Z., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In traditional Chinese medicinal practices, Gegen (GG) and Tianma (TM) are widely utilized for headache relief, but their material basis has not been comprehensively characterized. This research utilized ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) for precise determination of Gegen-Tianma's (GGTM) material composition, and employed desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to pinpoint the brain-absorbed components and various metabolites post oral administration to rats. A total of 80 chemical constituents were identified from GGTM, 11 prototypes and 18 metabolites were identified from plasma. The brain tissue was identified in total 4 prototypes and 5 metabolites, these constituents were basically located in the prefrontal cortex and thalamus. The absorption patterns of components in the rat brain aligned with the varied distribution of metabolites within the brain. This study provides a solid theoretical basis for in-depth exploration of potential drug targets and elucidation of the specific mechanism of action of GGTM in the treatment of migraine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia-reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Chronic heart failure (CHF) is a severe consequence of cardiovascular disease, marked by cardiac dysfunction. Jin-Xin-Kang (JXK) is a traditional Chinese herbal formula used for the treatment of CHF. This formula consists of seven medicinal herbs, including Ginseng (Ginseng quinquefolium (L.) Alph.Wood), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge), Salvia miltiorrhiza (Salvia miltiorrhiza Bunge), Descurainiae Semen Lepidii Semen (Descurainia sophia (L.) Webb ex Prantl), Leonuri Herba (Leonurus japonicus Houtt.), Cinnamomi Ramulus (Cinnamomum cassia (L.) J.Presl), and Ilex pubescens (Ilex pubescens Hook. & Arn.). Its clinical efficacy has been validated through prospective randomized controlled studies. However, the specific mechanisms of action for this formula have yet to be elucidated., Aim of the Study: This study aimed to investigate the effect of JXK on mitochondrial function and its mechanism in the treatment of CHF., Methods: JXK components were qualitatively analyzed using UPLC-Q-Orbitrap-MS. HF was induced in mice via transverse aortic constriction (TAC). After successful model establishment, lyophilized JXK-L (4.38 g/kg) and JXK-H (13.14 g/kg) were administered for 8 weeks. In vitro, hypertrophic myocardium was induced using angiotensin II (Ang II) for 48 h, followed by JXK-L and JXK-H treatment. Network pharmacology and molecular docking techniques were used to predict the relevant targets of JXK. Cardiac function, serum markers, and histopathological changes were evaluated to assess cardiac function. Immunofluorescence of Tomm20, mitochondrial membrane potential, and ROS were measured to assess mitochondrial dysfunction. Protein expression of calcineurin (CaN) and Drp1 in the myocardium was assessed by Western blot analysis., Results: We detected that the active components of JXK include terpenes, glycosides, flavonoids, amino acids, and alkaloids, among others. In mice with CHF, JXK improved cardiac function and reversed ventricular remodeling. Network pharmacology indicated that JXK can inhibit the calcium signaling pathway. The molecular docking results demonstrated that the active components of JXK effectively bind with CaN. Both in vitro and in vivo experiments confirmed that JXK regulated the CaN/Drp1 pathway and alleviated mitochondrial dysfunction., Conclusion: JXK can inhibit the CaN/Drp1 pathway to improve mitochondrial function, and consequently treat CHF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Trichosanthes kirilowii-Allium macrostemon (Chinese name Gualou and Xiebai, GLXB), a classical herb pair, has significant clinical efficacy in the treatment of myocardial ischemia (MI). In this study, network pharmacology combined with RNA-seq strategy was employed to predict the targets and pathways of GLXB for MI. GLXB significantly modulated signaling pathways related to the pathology of MI, such as anti-inflammatory and anti-apoptotic signaling pathways such as WNT, PI3K/AKT, and AMPK. GSEA showed that GLXB administration downregulated these key pathways. In addition, Metabolomic analysis demonstrated that GLXB treatment reversed metabolic disorder. Integrative analysis demonstrated three key metabolites (pyruvate, lactate, and palmitate) and three differential genes (Pck1, Cdo1, and Cth) that affected glycolysis or gluconeogenesis and cysteine and methionine metabolism. The results of molecular docking showed that chrysin-7-O-glucuronide and diosmetin-7-O-rutinoside may be the crucial components that exert myocardial protective activity. Western blot showed that GLXB administration reversed the expression levels of Pck1, Cdo1, Cth, Alb, Bcl2, and Ccnd1. This study has elucidated that GLXB could alleviate MI in rats by modulating WNT and PI3K/AKT signaling pathways, thereby reducing inflammation and apoptosis as well as improving energy metabolism., (© 2024 John Wiley & Sons Ltd.)

Context: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use., Objective: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases., Methods: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence., Results: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment., Conclusions: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml -1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 ., (© 2024. The Author(s).)

Background: The activation of the NLRP3 inflammasome has recently been revealed as a novel pathological mechanism of coronary heart disease (CHD). The Dan-Lou tablets (DLT) is widely used in the clinical treatment of CHD and prescription characterized by multi-component and multi-target regulation. However, the anti-inflammatory mechanism of DLT in the treatment of CHD remains unclear., Purpose: This study aimed to evaluate the effect of DLT in the treatment of CHD on the priming and activation of the NLRP3 inflammasome and to investigate the underlying anti-inflammatory mechanisms., Methods: First, CHD rats model were established by a high-fat diet combined with left anterior coronary artery ligation (LADCA) followed by DLT intervention. The therapeutic effect of DLT was evaluated according to cardiac function, lipid level, and cardiac histopathology. Next, data-independent acquisition (DIA) proteomics was used to identify the key differential proteins of DLT intervention in CHD rats, and bioinformatics analysis was performed. Finally, the differentially expressed proteins in the NOD-like signaling pathway were verified based on bioinformatics results, and the priming and activation steps of the NLRP3 inflammasome were detected., Results: In this study, a high-fat diet combined with LADCA was utilized to generate a CHD model, and DLT alleviated myocardial ischemia injury by inhibiting lipid deposition and inflammatory response. Proteomic studies observed that the RNF31, TXN2, and GBP2 of the NOD-like receptor signaling pathway were verified as the key targets of DLT in inhibiting myocardial injury in CHD rats. Furthermore, DLT in the treatment of CHD rats may function through the downregulation of P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and may then reduce the release of the IL-1β and IL-18 inflammatory factors to play an anti-myocardial injury effect., Conclusion: Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD. This study innovatively proposed that DLT further exerts an anti-myocardial injury effect by inhibiting P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and then downregulates the release of the IL-1β and IL-18 inflammatory factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Purpose: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length., Study Design and Methods: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length., Results: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator., Conclusions: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging., Trial Registry: https://www.chictr.org.cn/showproj.html?proj=166181., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear., Aim of the Study: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research., Methods: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining., Results: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCβ, IKKβ, GSK3β, c-Fos and NF-κB p65 proteins., Conclusion: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Fangji Huangqi Decoction (FHD) is frequently prescribed for the clinical treatment of wind-cold and wind-dampness pathogenic superficial deficiency syndrome. It also has a notable curative effect on rheumatoid arthritis (RA)., Aim of the Study: The study aimed to explore the possible mechanism of FHD against RA and provided a theoretical basis for alternative therapies for RA., Materials and Methods: We used UPLC-Q-TOF-MS to analysis the ingredients and absorbed blood components of FHD. At the same time, the collagen-induced arthritis (CIA) rat model was established to estimate the therapeutic effects on FHD by considering body weight, arthritis score, paw swelling, autonomous movement ability, and synovial microvessel counts. Subsequently, immunofluorescence, immunohistochemistry, and Western blot were employed to detect the anti-angiogenic capacity of FHD in vivo, as well as the levels of apoptosis and autophagy in the synovial tissue. In addition, flow cytometry and Western blot were used to assess the effects of FHD on apoptosis and autophagy in MH7A cells. The effects of FHD on the proliferation and migration of MH7A cells were measured by CCK8 assay, cell migration and, invasion experiments. Finally, a tube formation assay was performed to evaluate the angiogenic capacity of FHD in co-cultures of MH7A cells and HUVEC cells., Results: Through testing of FHD's original formula, a total of 26 active ingredients have been identified, with 17 of them being absorbed into the bloodstream. FHD significantly improved the pathological symptoms and synovial hyperplasia of CIA rats. FHD could suppress the expression of HIF-1α, promote apoptosis in CIA rat synovial tissue, and suppress autophagy and angiogenesis. In vitro experiments showed that serum containing FHD inhibited the proliferation, migration, and invasion of MH7A cells, and also suppressed the expression of autophagy-related proteins while promoting apoptosis. FHD markedly repressed the expression of HIF-1α protein in TNF-α-stimulated MH7A cells and inhibited the tube formation capacity induced by MH7A cells in HUVEC cells., Conclusions: The study had proven that FHD played an excellent anti-RA role, which may be attributed to its potential mechanism of regulating the balance between autophagy and apoptosis in RA FLS by suppressing the HIF-1α, thus contributing to its anti-angiogenic activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Shanxi University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) presents a significant challenge due to its prevalence and lack of cure, driving the quest for effective treatments. Anshen Bunao Syrup, a traditional Chinese medicine known for its neuroprotective properties, shows promise in addressing this need. However, understanding its precise mechanisms in AD remains elusive. This study aimed to investigate Anshen Bunao Syrup's therapeutic potential in AD treatment using a scopolamine-induced AD rat model. Assessments included novel-object recognition and Morris water maze tasks to evaluate spatial learning and memory, alongside Nissl staining and ELISA analyses for neuronal damage and biomarker levels. Results demonstrated that Anshen Bunao Syrup effectively mitigated cognitive dysfunction by inhibiting amyloid-β and phosphorylation Tau aggregation, thereby reducing neuronal damage. Metabolomics profiling of rats cortex revealed alterations in key metabolites implicated in tryptophan and fatty acid metabolism pathways, suggesting a role in the therapeutic effects of Anshen Bunao Syrup. Additionally, ELISA and correlation analyses indicated attenuation of oxidative stress and immune response through metabolic remodeling. In conclusion, this study provides compelling evidence for the neuroprotective effects of Anshen Bunao Syrup in AD models, shedding light on its potential as a therapeutic agent for AD prevention and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula., Purpose: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD)., Methods: Initially, the chemical profile of ZXG was systemically characterized. Subsequently, the representative constituents were quantitatively analyzed. In the third step, the multi-component xenobiotics profile of ZXG was systemically delineated, and the prototypes absorbed into the blood were identified and designated as the primary bioavailable components. Next, an integrated network of "bioavailable components-CHD targets-pathways-therapeutic effects" was constructed, and the crucial bioavailable components of ZXG against CHD were screened out. Lastly, the bioactivities of crucial bioavailable components were further evaluated to pinpoint effective components., Results: First of all, the chemical profile of ZXG was systemically characterized with the detection of 201 components. Secondly, 37 representative components were quantified to comprehensively describe its content distribution characteristics. Thirdly, among the quantified components, 24 bioavailable components of ZXG were identified based on the multi-component xenobiotic profile. Fourthly, an integrated network led to the identification of 11 crucial bioavailable components against CHD. Ultimately, 9 components (honokiol, magnolol, naringenin, magnoflorine, hesperidin, hesperetin, naringin, neohesperidin and narirutin) exhibiting myocardial protection in vitro were identified as effective components of ZXG for the first time., Conclusion: Overall, this innovative strategy successfully identified the effective components of ZXG for the first time. It could not only significantly contribute to elucidating the therapeutic mechanism of ZXG in the treatment of CHD, but also serve as a helpful reference for the systematic discovery of effective components as well as ideal quality markers in the quality assessment of TCM formulas., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8‑week 2% NaCl‑feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD‑associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/β‑catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt‑induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/β‑catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E&#95;2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E&#95;2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.

Natural Killer (NK) cell is the first batch of re-constructed cell populations after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and its delayed reconstitution inevitably causes poor outcome. The traditional Chinese medicine Huiyang-Guben decoction (HYGB) has been clinically used in patients undergoing allo-HSCT, but its effect on NK cell reconstruction is still unclear. 40 patients with allo-HSCT therapy were randomly divided into the control group and the HYGB group, and were given oral administration of normal saline or HYGB for 4 weeks before allo-HSCT, respectively. NK cells were cultured and treated with transforming growth factor β (TGF-β) and HYGB in vitro, and cell viability, cell apoptosis, and the function of NK cells were evaluated. Functional verification experiments were performed by knocking down signal transduction molecule 7 (Smad7) in NK cells before TGF-β and HYGB treatment. Clinical data suggested that HYGB intervention decreased the incidence of acute graft-versus-host disease after allo-HSCT, and increased the proportion of NK cell population. Meanwhile, HYGB improved cell viability, restrained apoptotic cell death, and enhanced cell killing activity of NK cells in patients with allo-HSCT. Notably, we found that HYGB significantly increased the expression level of Smad7 and the phosphorylation level of signal transducer and activator of transcription 3 (Stat3) in NK cells from patients with allo-HSCT. Moreover, HYGB alleviated TGF-β-induced NK cell impairment and re-activated the Smad7/Stat3 signaling in vitro, while silencing Smad7 reversed the protective effect of HYGB on TGF-β-treated NK cells. HYGB promotes NK cell reconstruction and improves NK cell function after allo-HSCT through activating the Smad7/Stat3 signaling pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethnopharmacological Relevance: Of all primary liver cancer cases, hepatocellular carcinoma (HCC) accounts for about 90%. Most patients with HCC receive a diagnosis in the medium-to-late stages or with chronic liver disease, have lost the opportunity for radical treatment, such as surgical resection, and their 5-year survival rate is low. Qizhu Anticancer Prescription (QZACP) is an empirical formula composed of traditional Chinese herbs that can clinically relieve HCC symptoms, inhibit the progression of HCC, reduce recurrence rate, and prolong survival; however, its exact mode of action remains unknown., Aim of the Study: This study's purpose was to investigate the mode of action of QZACP in the prevention and treatment of HCC., Materials and Methods: Initially, drug components in the QZACP decoction were analyzed using high-resolution mass spectrometry. A subcutaneous tumor xenograft model in nude mice was constructed to further analyze the active components of QZACP that had entered tumor tissues through oral administration. Potential targets of QZACP in the prevention and treatment of HCC were identified and then confirmed in vivo via network pharmacology and molecular docking. In addition, regulatory effects of QZACP on HCC cell proliferation and the cell cycle were detected using a CCK-8 assay and flow cytometry., Results: High-resolution mass spectrometry revealed that the QZACP decoction contained deacetyl asperulosidic acid methyl ester (DAAME), paeoniflorin, calycosin-7-glucoside, liquiritin, glycyrrhizic acid, astragaloside IV, saikosaponin A, curdione, and atractylenolide II. In nude mice, QZACP could effectively inhibit the growth of subcutaneous tumors, where DAAME, paeoniflorin, liquiritin, and glycyrrhizic acid could enter liver cancer tissues after oral administration. Among these, DAAME was the most highly expressed in HCC tissues and may be an important active component of QZACP for inhibiting HCC. Utilizing network pharmacology, the targets of action of these four drug components were identified. After verification using western blotting, STAT3, VEGFA, JUN, FGF2, BCL2L1, AR, TERT, MMP7, MMP1, ABCB1, CA9, and ESR2 were identified as targets of QZACP inhibition in HCC. In vitro experiments revealed that QZACP inhibited the proliferation of HCC cells while inducing G0/G1 phase cell cycle arrest. In vivo experiments demonstrated that DAAME significantly inhibited HCC growth. After intersection of the 24 DAAME targets predicted using network pharmacology with the 435 HCC disease targets, only CA9 was identified as a DAAME-HCC crossover target. Molecular docking results revealed that the binding site of DAAME and CA9 had good stereo-complementarity with a docking score of -8.1 kcal/mol. Western blotting and immunohistochemical results also confirmed that DAAME significantly decreased CA9 protein expression in HCC., Conclusions: QZACP inhibits HCC by reducing the expression of STAT3, VEGFA, JUN, FGF2, BCL2L1, AR, TERT, MMP7, MMP1, ABCB1, CA9, and ESR2. DAAME may be an important active component of QZACP for the prevention and treatment of HCC, inhibiting it by targeting the expression of CA9., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quantitative analysis of the quality constituents of Lonicera japonica (Jinyinhua [JYH]) using a feasible method provides important information on its evaluation and applications. Limitations of sample pretreatment, experimental site, and analysis time should be considered when identifying new methods. In response to these considerations, Raman spectroscopy combined with deep learning was used to establish a quantitative analysis model to determine the quality of JYH. Chlorogenic acid and total flavonoids were identified as analysis targets via network pharmacology. High performance liquid chromatograph and ultraviolet spectroscopy were used to construct standard curves for quantitative analysis. Raman spectra of JYH extracts (1200) were collected. Subsequently, models were built using partial least squares regression, Support Vector Machine, Back Propagation Neural Network, and One-dimensional Convolutional Neural Network (1D-CNN). Among these, the 1D-CNN model showed superior prediction capability and had higher accuracy (R 2  = 0.971), and lower root mean square error, indicating its suitability for rapid quantitative analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.

Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD. Second, we analyzed the active compounds of BSNXD and predicted their potential mechanisms for POI-related osteoimmune disorder via network pharmacology, further confirmed by molecular biology experiments. The results demonstrated that VCD exposure led to elevated follicle-stimulating hormone (FSH) levels, a 50% reduction in the primordial follicles, bone microstructure changes, and macrophage activation, indicating an osteoimmune disorder. BSNXD inhibited macrophage activation and osteoclast differentiation but did not affect serum FSH and estradiol levels in the VCD-induced POI model. Network pharmacology predicted the potential mechanisms of BSNXD against the POI-related osteoimmune disorder involving tumor necrosis factor α and MAPK signaling pathways, highlighting BSNXD regulated inflammation, hormone, and osteoclast differentiation. Further experiments identified BSNXD treatment suppressed macrophage activation via downregulating FSH receptor (FSHR) expression and inhibiting the phosphorylation of ERK and CCAAT enhancer binding proteins β. In conclusion, BSNXD regulated POI-related osteoimmune disorder by suppressing the FSH/FSHR pathway to reduce macrophage activation and further inhibiting osteoclastogenesis.

Objective: To evaluate the clinical efficacy of Xiaozheng Granules (XZG) combined with Jingqiankang Bacteriostatic Gelatin (JBG) on chronic prostatitis of the damp-heat and blood-stasis type based on infrared thermography (IRT)., Methods: This study included 120 cases of chronic prostatitis with damp-heat and blood stasis treated in the First Affiliated Hospital of Henan University of Chinese Medicine with oral XZG (the control group, n = 60) or oral XZG combined with anal administration of JBG (the trial group, n = 60), both for 4 weeks. We obtained the NIH-CPSI and traditional Chinese medicine (TCM) syndrome scores of the patients, measured the temperatures in the belt-vessel, lower focal and inguinal regions by IRT before and after treatment, recorded the adverse reactions during the treatment, and compared them between the two groups of patients., Results: Compared with the baseline, the NIH-CPSI and TCM syndrome scores were significantly decreased in the two groups of patients after treatment (P < 0.05), even more significantly in the trial than in the control group (P < 0.05), and after 1 hour of treatment, the temperatures in the Xiajiao (［34.09 ± 0.34］ vs ［33.60 ± 0.40］ ℃, P < 0.05) and the groin region (［34.49 ± 0.28］ vs ［33.78 ± 0.30］ ℃, P < 0.05) were remarkably reduced in the trial group, but showed no significant change in the control group (Xiajiao region: ［34.02 ± 0.29］ vs ［34.05 ± 0.26］ ℃, P > 0.05; groin region: ［34.54 ± 0.25］ vs ［34.51±0.22］ ℃, P > 0.05). After 4 weeks of treatment, the temperatures in the Xiajiao and groin regions were even lower in the trial (［33.13 ± 0.41］ ℃ and ［33.21 ± 0.29］ ℃) and the control group (［33.42±0.25］ ℃ and ［33.86±0.29］ ℃) than the baseline and those after 1 hour of treatment (P < 0.05), and still more significantly in the former than in the latter group (P < 0.05). The total effectiveness rate was markedly higher in the trial group than in the control (88.14% vs 77.19%, P < 0.05), and no obvious adverse reactions were observed in neither group., Conclusion: XZG combined with JBG is a safe and effective treatment of chronic prostatitis with damp-heat and blood-stasis, which can significantly reduce the NIH-CPSI and TCM syndrome scores and IRT temperatures in the lower focal and inguinal regions of the patients.

Thromboangiitis obliterans (TAO) is a rare, chronic, progressive, and segmental inflammatory disease characterized by a high rate of amputation, significantly compromising the quality of life of patients. Si-Miao-Yong-An decoction (SMYA), a traditional prescription, exhibits anti-inflammatory, anti-thrombotic, and various other pharmacological properties. Clinically, it was fully proved to be effective for TAO therapy, but the specific therapeutic effect of SMYA on TAO has been unknown. Thus, deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important. In this study, we observed elevated levels of IL-17A in the peripheral blood mononuclear cells (PBMCs) of TAO patients, whereas the expression of miR-548j-5p was significantly decreased. A negative correlation between the levels of miR-548j-5p and IL-17A was also demonstrated. In vitro experiments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels, whereas downregulation of miR-548j-5p showed the opposite effect. Using a dual luciferase assay, we confirmed that miR-548j-5p directly targets IL-17A. Furthermore, serum containing SMYA effectively decreased IL-17A levels by increasing the expression of miR-548j-5p. More importantly, the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular tissues. In conclusion, SMYA significantly enhances the expression of miR-548j-5p, thereby reducing the levels of the target gene IL-17A and alleviating TAO. Our research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Based on the insulin receptor substrate(IRS)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) pathway, the intervention effect of Yupingfeng Powder on type 2 diabetes mellitus(T2DM) rats was studied, and the potential mechanism of improving T2DM hepatic insulin resistance was explored. A T2DM rat model was established by feeding with high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin. Successfully modeled rats were selected and divided into a model group, a positive control group(MET), and a Yupingfeng Powder group. At the same time, a blank group was set up, and corresponding drugs were given by gavage. The model group and blank group were given an equal amount of physiological saline by gavage. During the experiment, body mass and fasting blood glucose were regularly measured, and glucose tolerance and insulin tolerance were measured at the end of the experiment. After the experiment, the levels of blood glucose, insulin, blood lipids, and related liver function indicators were measured; changes in liver pathological damage were observed, levels of liver monoamine oxidase were detected, and qRT-PCR was used to detect mRNA expression levels of IRS/PI3K/Akt pathway related genes. Compared with the model group, the Yupingfeng Powder group had an increase in body weight, a decrease in fasting blood glucose, fasting insulin, and steady-state model evaluation index, a decrease in the area under the curve of glucose tolerance and insulin tolerance tests, a decrease in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol content, and an increase in high-density lipoprotein cholesterol content. Compared with the model group, the Yupingfeng Powder group showed a decrease in liver monoamine oxidase levels, a decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and an increase in total protein and albumin levels. Hematoxylin-eosin(HE) staining showed a reduction in pathological liver cell damage. Compared with the model group, the Yupingfeng Powder group showed a significant increase in the mRNA expression levels of IRS1, PI3K, and Akt in the liver of rats, as well as a significant decrease in the mRNA expression levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). This indicates that Yupingfeng Powder can regulate the IRS/PI3K/Akt signaling pathway and glucose and lipid metabolism disorders, increase insulin sensitivity, improve hepatic insulin resistance, and thus play a therapeutic role in T2DM.

Background: Danggui Longhui is a traditional Chinese medicine made from the dried root of Angelica sinensis. It is used in psychiatric patients in China to reduce associated constipation. In a population pharmacokinetic model in olanzapine patients from Beijing Anding Hospital, we demonstrate that dangguilonghui tablets doubled olanzapine clearance, indicating the induction of olanzapine metabolism. Olanzapine metabolism is similar to clozapine metabolism., Methods: Two cases of possible clozapine induction using dangguilonghui tablets 4 g/day were identified in Beijing Anding Hospital. Dividing the minimum therapeutic concentration of 350 ng/mL by the concentration-to-dose (C/D) ratio provides the minimum therapeutic dose., Results: Case 1 was a female smoker on clozapine for 415 days. The mean of 6 clozapine C/D ratios associated with smoking provided a minimum therapeutic dose of 267 mg/day. There were 6 steady-state concentrations on the combination of valproic acid and dangguilonghui tablets, which provided a much higher minimum therapeutic dose of 833 mg/day. Four steady-state clozapine C/D ratios based on smoking and valproate after 4 months of carbamazepine 200 mg/day provided a minimum therapeutic dose of 603 mg/day. Case 2 was a female non-smoker on clozapine for 58 days. She had 3 clozapine C/D ratios on dangguilonghui tablets with a mean of 0.30 ng/mL providing a minimum therapeutic dose of 1167 mg/day., Conclusion: Future clinical studies with repeated measures need to replicate the possibility that dangguilonghui tablets are a moderate-to-strong inducer of clozapine metabolism as suggested by these two limited cases., Competing Interests: Declaration of competing interest In the last 3 years, all authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia., Methods: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg -1 •d -1 ), MPA + low-dose (20 mg•kg -1 •d -1 ) JP (L-JP), MPA + medium-dose (30 mg•kg -1 •d -1 ) JP (M-JP), and MPA + high-dose (40 mg•kg -1 •d -1 ) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase., Results: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro., Conclusions: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease., Methods: BV-2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid-β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration., Results: The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL-1β, TNF-α, and iNOS; increased the expression level of IL-10; and significantly decreased the phosphorylation levels of MAPK and NF-κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL-1β and TNF-α in the cortex were significantly downregulated after JHP administration, whereas IL-10 showed increased expression., Conclusions: It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Ethnopharmacological Relevance: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown., Aim of the Study: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms., Materials and Methods: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders., Results: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders., Conclusions: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rational: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication., Methods: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD., Results: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other., Conclusion: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication., (© 2024 John Wiley & Sons Ltd.)