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Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) on a global scale has created a pressing demand for novel treatments. Gentianella turkestanorum (Gand.) Holub, a traditional Chinese herbal medicine, has been found to possess hypoglycemic effects. However, the mechanism of its action remains unclear. Objectives: This study was to investigate the impact and mechanism of G. turkestanorum 's water extract (WEG) in reducing insulin resistance (IR) in T2DM. Materials and Methods: Db/db mice were administered WEG for 8 weeks, during which their body weight, blood glucose (BG), oral glucose tolerance test, islet tolerance test, fasting insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein were monitored. Additionally, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in db/db mice were measured using enzyme-linked immunosorbent assay (ELISA). The study also evaluated the impact of WEG on liver injury through hematoxylin-eosin staining. The expression levels of key proteins and genes in both insulin signaling and inflammation-related pathways were detected using western blotting and real-time quantitative polymerase chain reaction. Results: WEG has the potential to regulate glycolipid metabolism, reduce inflammation, and alleviate IR. The mechanism of action may involve promoting the insulin signaling pathway and inhibiting inflammation. Conclusion: Gentianella turkestanorum could be a viable treatment option for T2DM and IR. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied. Methods: A mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways. Results: The results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR. Conclusions: QRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients. [ABSTRACT FROM AUTHOR]

The property theory is a unique principle instructing traditional Chinese doctors to prescribe proper medicines against diseases. As an essential part of it, the five-flavor theory catalogs various Chinese materia medicas (CMMs) into five flavors (sweet, bitter, sour, salty, and pungent) based on their taste and medical functions. Although CMM has been successfully applied in China for thousands of years, it is still a big challenge to interpret CMM flavor via modern biomarkers, further deepening its elusiveness. Herein, to identify the correlation between gut microbiota and CMM flavor, we selected 14 CMMs with different flavors to prepare their aqueous extracts, quantified the contained major chemical components, and then performed full-length 16S rRNA sequencing to analyze the gut microbiota of C57BL/6 mice administrated with CMM extracts. We found that flavones, alkaloids, and saponins were the richest components for sweet-, bitter-, and pungent-flavored CMMs, respectively. Medicines with merged flavors (bitter-pungent and sweet-pungent) displayed mixed profiles of components. According to gut microbial analysis, modulation of CMMs belonging to the same flavor on the taxonomic classification was inconsistent to an extent, while the functional sets of gut microbiota, co-abundance gene groups (CAGs), strongly and differentially responded to distinct flavors. Moreover, these correlations were in line with their pharmacological actions. Therefore, the gut microbial functional sets (CAGs) could act as the possible indicator to reflect CMM flavor, rather than the composition of microbial community. [ABSTRACT FROM AUTHOR]

Introduction: Disseminated intravascular coagulation (DIC) is a syndrome characterized by coagulopathy, microthrombus, and multiple organ failure. The complement system in DIC is overactivated, and the functions of complement and coagulation pathways are closely related. Our previous screening revealed that salvianolic acid A (SAA) has anti-complement activity. The hyper-activated complement system was involved in the lipopolysaccharide (LPS) induced DIC in rats. The effects of SAA anti-complement action on LPS-induced DIC in rats were investigated. Methods: The complement activity of the classical pathway and alternative pathway was detected through an in vitro hemolysis assay. The binding sites of SAA and complement C3b were predicted by molecular docking. LPS-induced disseminated coagulation experiments were performed on male Wistar rats to assess coagulation function, complement activity, inflammation, biochemistry, blood routine, fibrinolysis, and survival. Results: SAA had an anti-complement activity in vivo and in vitro and inhibited the complement activation in the classical and alternative pathway of complement. The infusion of LPS into the rats impaired the coagulation function, increased the plasma inflammatory cytokine level, complemented activation, reduced the clotting factor levels, fibrinogen, and platelets, damaged renal, liver, and lung functions, and led to a high mortality rate (85%). SAA treatment of rats inhibited complement activation and attenuated the significant increase in D-dimer, interleukin-6, alanine aminotransferase, and creatinine. It ameliorated the decrease in plasma levels of fibrinogen and platelets and reversed the decline in activity of protein C and antithrombin III. The treatment reduced kidney, liver, and lung damage, and significantly improved the survival rate of rats (46.2 and 78.6% for the low- and high-dose groups, respectively). Conclusion: SAA reduced LPS-induced DIC by inhibiting complement activation. It has considerable potential in DIC treatment. [ABSTRACT FROM AUTHOR]

A new series of C-14 curcumol derivatives as potent anticancer agents were designed and synthesized by click reaction, whose structures were confirmed by 1H NMR,13C NMR, and HRMS analysis. All the synthesized compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620 and HCT116. Most of them exhibited higher inhibitory activity than curcumol. Especially, compound 3j shows good inhibitory activity against SW620 with IC50 value of 8.10 ± 0.13 μM. The structure–activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry revealed that compound 3j induced SW620 cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that fluorine functional group on phenyl ring tended to increase the anticancer activity. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. Materials and Methods. The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. Results. The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. Conclusion. The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine (BBR) have been extensively used for centuries in Ayurvedic and traditional Chinese medicine. The goal of this systematic review is to investigate the preclinical evidence of BBR on NAFLD models. The following relevant databases, including Web of Science, PubMed, the Cochrane Library, and Embase, were retrieved from inception to May 2021. The content involved BBR on different animal models for the treatment of NAFLD. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) Animal Experiment Bias Risk Assessment Tool was used to assess the methodological quality and RevMan 5.4 software was used to conduct the meta-analysis based on the Cochrane tool. A total of 31 studies involving 566 animals were included, of which five models and five animal breeds were reported. The results showed that TC, TG, ALT, AST, HDL-C, LDL-C, FBG, FINS, and FFA in the group treated with BBR were significantly restored compared with those in the model group. HOMA-IR had a significant downward trend, but the result was not significantly different (P = 0.08). The subgroup analysis of the different models and different animal breeds indicated that BBR could ameliorate the aforementioned indicator levels, although some results showed no significant difference. Finally, we summarized the molecular mechanisms by which berberine regulated NAFLD/NASH, mainly focusing on activating the AMPK pathway, improving insulin sensitivity and glucose metabolism, regulating mitochondrial function, reducing inflammation and oxidative stress, regulating cell death and ER stress, reducing DNA methylation, and regulating intestinal microenvironment and neurotoxicity. The preclinical evidence suggested that BBR might be an effective and promising drug for treating NAFLD/NASH. In addition, further studies with more well-designed researches are needed to confirm this conclusion. [ABSTRACT FROM AUTHOR]

Background. Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active components and mechanisms of ZJP are still arcane. This study aimed to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC. Methods. Firstly, the components and putative targets of ZJP were collected based on herbal medicine target databases, and a network containing the interaction between the targets of ZJP and the potential therapeutic targets of UC was established. Then, topological parameters were calculated to identify the key targets in the network and, in turn, to import them into the David database to perform path enrichment analysis. Results. 14 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, MAPK cascade, inflammatory response, immune response, and the apoptotic process of UC. Moreover, the PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway, and Prolactin signaling pathway were predicted to participate in ZJP treating UC. Among them, 14 active components of ZJP directly regulate these pathways. Conclusion. ZJP could alleviate UC through the predicted components and mechanisms. The 14 predicted active components of ZJP may mainly play a therapeutic role for UC through synergistic regulation of the PI3K-Akt signaling pathway and MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Airway remodeling is one of the typical pathological characteristics of asthma, while the structural changes of the airways in asthma are complex, which impedes the development of novel asthma targeted therapy. Our previous study had shown that Bu-Shen-Yi-Qi formula (BSYQF) could ameliorate airway remodeling in chronic asthmatic mice by modulating airway inflammation and oxidative stress in the lung. In this study, we analysed the lung transcriptome of control mice and asthmatic mouse model with/without BSYQF treatment. Using RNA-sequencing (RNA-seq) analysis, we found that 264/1746 (15.1%) of transcripts showing abnormal expression in asthmatic mice were reverted back to completely or partially normal levels by BSYQF treatment. Additionally, based on previous results, we identified 21 differential expression genes (DEGs) with fold changes (FC) > (±) 2.0 related to inflammatory, oxidative stress, mitochondria, PI3K/AKT, and MAPK signal pathways which may play important roles in the mechanism of the anti-remodeling effect of BSYQF treatment. Through inputting 21 DEGs into the IPA database to construct a gene network, we inferred Adipoq, SPP1, and TNC which were located at critical nodes in the network may be key regulators of BSYQF's anti-remodeling effect. In addition, the quantitative real-time polymerase chain reaction (qRT-PCR) result for the selected four DEGs matched those of the RNA-seq analysis. Our results provide a preliminary clue to the molecular mechanism of the anti-remodeling effect of BSYQF in asthma. [ABSTRACT FROM AUTHOR]

Background. Scutellaria baicalensis (SB) is commonly used in traditional Chinese medicine for chronic inflammatory diseases. This study aims to investigate the effects of the early intervention with SB on airway remodeling in a well-established rat model of COPD induced by cigarette smoking. Methods. COPD model in Sprague Dawley (SD) rats were established by exposing them to smoke for 6 days/week, for 12 weeks, 24 weeks, or 36 weeks. Meanwhile, rats were randomly divided into normal control group, model group, Budesonide (BUD) group, and the SB (low, middle, and high) dose groups with 8 rats in each group and 3 stages (12 weeks, 24 weeks, and 36 weeks). After treatment, the pulmonary function was evaluated by BUXCO system and the morphology changes of the lungs were observed with HE and Masson staining. The serum IL-6, IL-8, and IL-10 and TNF-α, TGF-beta (TGF-β1), MMP-2, MMP-9, and TIMP-1 levels in BALF were detected by ELISA-kit assay. The protein expression levels of AKT and NF-κB (p65) were determined by western blot (WB). Results. The oral of SB significantly improved pulmonary function (PF) and ameliorated the pathological damage and attenuated inflammatory cytokines infiltration into the lungs. Meanwhile, the levels of TGF-β, MMP-2, MMP-9, and TIMP-1 were partially significantly decreased. The levels of PI3K/AKT/NF-κB pathway were also markedly suppressed by SB. Conclusions. SB could significantly improve the condition of airway remodeling by inhibiting airway inflammation and partially quenching TGF-β and MMPs via PI3K/AKT/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that Qing-Re-Huo-Xue (QRHX) formulae had significant anti-inflammatory effects in chronic airway diseases such as asthma and chronic obstructive lung disease. Here, we examined the effects of QRHX on lung cancer cell invasion and the potential associated mechanism(s), mainly polarization of macrophages in the tumor microenvironment. In vivo, QRHX both inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in mice with lung cancer. Further study indicated that QRHX inhibited cancer-related inflammation in tumor by decreasing infiltration of TAMs and IL-6 and TNF-α production and meanwhile decreased arginase 1 (Arg-1) expression and increased inducible NO synthase (iNOS) expression. QRHX could markedly inhibit CD31 and VEGF protein expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced in QRHX treatment group. Thus, we draw that QRHX played a more important role in inhibiting tumor growth by regulating TAMs in mice, which was found to be associated with the inhibition of inflammation and the CXCL12/CXCR4/JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bu-Shen-Yi-Qi formulae (BSYQF) are frequently used in the treatment of chronic inflammatory diseases in the respiratory system in traditional Chinese medicine (TCM). However, the regulatory effect of BSYQF on T helper 17 (Th17) and regulatory T (Treg) cells in murine ovalbumin (OVA) asthma model remains poorly understood. In the present study, we sought to determine the effect of high-performance liquid chromatography/mass spectrometry (HPLC/MS) standardized BSYQF on chronic airway inflammation and Th17/Treg imbalance in the murine OVA asthma model. Materials and methods The murine asthma model was induced by OVA sensitization and challenge and BSYQF was oral administrated. 24 h after last OVA exposure, airway hyperresponsiveness (AHR) to methacholine (Mch) was assessed, and inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were analysed. Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining. Th17 and Treg associated cytokine levels in serum and BALF as well as transcription factors expression in the lung tissue were measured by ELISA, Bio-Plex and western blot assay. We also analysed the CD4 + RORγt + and CD4 + Foxp3 + T cells in BALF and spleen by flow cytometric analysis. Results Our results demonstrated that oral administration of BSYQF inhibited the markedly increased AHR and lung inflammation ( p <0.05), resulted in a dramatic reduction in total inflammatory cells as well as neutrophils (Neu), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos) and basophils (Bas) of OVA-induced asthmatic mice ( p <0.05). Furthermore, BSYQF treatment caused a distinct reduction in IL-6, IL-10 and IL-17A levels in serum ( p <0.05), and induced a significant improvement in IL-6 and IL-10 as well as a marked decrease in TGF-β1 and IL-17A levels in BALF of OVA-induced asthmatic mice ( p <0.05). Mice in BSYQF treated groups also had decreased RORγt and increased Foxp3 expression in the lung tissue ( p <0.05). Flow cytometry analysis revealed that CD4 + RORγt + T cells elevated markedly and CD4 + Foxp3 + T cells decreased prominently in BALF and spleen in murine OVA asthma model ( p <0.05), and BSYQF and DEX treatment lead to an obvious reduction in CD4 + RORγt + T cells in BALF ( p <0.05) but not in spleen. BSYQF and DEX treatment resulted in an obvious elevation in CD4 + Foxp3 + T cells in BALF and spleen ( p <0.05). Conclusions Collectively, these results demonstrated that BSYQF could suppress chronic airway inflammation and regulate Th17/Treg imbalance by inhibition of Th17 and enhancement of Treg functions in the murine OVA asthma model, which may help to elucidate the underlying regulatory mode of BSYQF on asthma treatment. [ABSTRACT FROM AUTHOR]

Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a toxic herb that can frequently cause fatal cardiac poisoning. Aconitum toxicity could be decreased by properly hydrolyzing diester-diterpene alkaloids into monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are the primary active and toxic constituents of processed Aconitum. Cytochrome P450 (CYP) enzymes protect the human body by functioning as the defense line that limits the invasion of toxicants. Our purposes were to identify the CYP metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish which isozymes are responsible for their metabolism through the use of chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution mass spectrometry was used to characterize the metabolites. A total of 7,8, and 9 metab olites were detected for BAC, BMA, and BHA, respectively. The main metabolic pathways were demethylation, dehydrogenation, demethylation-dehydrogenation, hydroxylation and didemethylation, which produced less toxic metabolites by decomposing the group responsible for the toxicity of the parent compound. Taken together, the results of the chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4 and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA. [ABSTRACT FROM AUTHOR]

Zuojin Pill (ZJP) has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. But its effect on non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric injury (GI) is still uncharted. This study aims to investigate the therapeutic effect and molecular mechanism of ZJP on indomethacin (IDO) induced gastric injury. GI was induced in rat by oral administration of 5 mg/kg IDO. Then the rats were treated with ZJP (1.26, 2.52, 5.04 g/kg, ig). The changes of food intake, body weight, gastric pH and general state observation were carried out to determine the improvement of ZJP in IDO-induced GI: HE staining and AB-PAS staining was analyzed to characterize the thickness of gastric mucosa and micro mucosal injury; in order to elucidate the effect of ZJP on IDO-induced inflammatory injury, the inflammatory infiltration of gastric tissue was observed by MPO immunohistochemical method, and the contents of TNF-α, IL-6 and IL-10 were measured. Furthermore, the regulatory mechanism of ZJP in treating IDO-induced GI was predicted with the help of network pharmacology, and the expression levels of key proteins ERK, p-ERK, P38, p-P38, JNK, p-JNK were determined to elucidate the molecular mechanism of ZJP. Current data strongly demonstrated that ZJP alleviated food intake reduction, weight loss and gastric injury caused by IDO and made gastric pH and mucosal thickness return to normal. In addition, ZJP could reduce the level of MPO to alleviate the inflammatory infiltration of gastric tissue. Simultaneously, ZJP could down regulate the expression of TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage caused by inflammatory, and create a healing environment. Furthermore, ZJP could significantly inhibit the phosphorylation of ERK, p38 and JNK, which leaded to the increase of inflammatory factors and the damage of gastric mucosa. ZJP improved local inflammation by inhibiting MAPK signaling pathway, and had a good therapeutic effect on IDO-induced GI. This study has reference significance for the study of ZJP in the prevention and treatment of NSAID induced gastric injury. In addition, ZJP may be a new treatment option for the prevention and treatment of NSAID induced gastric disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Systemic glucocorticoids are effective for the management of chronic obstructive pulmonary disease (COPD) exacerbation but have serious adverse effects. Traditional Chinese medicine (TCM) can bring additional benefits to these patients but has few adverse effects. The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime.Methods: In this multi-center, randomized, double-blinded trial, eligible inpatients with COPD exacerbation are randomly assigned to four groups (A, B, C, and D). Group A will receive placebo plus 5-day prednisone, group B will receive placebo plus 9-day prednisone, group C will receive JWBY formulas plus 5-day prednisone, and group D will receive JWBY formulas plus 9-day prednisone. The primary outcomes are the time interval to the patient's next exacerbation during a 180-day following up and the COPD assessment test (CAT) during treatment. Secondary outcomes include lung function, TCM syndrome assessment, laboratory tests, and safety. The changes of the hypothalamic pituitary adrenaline axis (HPA axis) and inflammatory cytokine will be measured as well.Discussion: By demonstrating the advantages of utilizing TCM and an appropriate duration of systemic glucocorticoids, this effectiveness comparison trial will provide new references to physicians on how to improve the management of COPD exacerbation. The results of HPA axis and inflammation cytokine measurements will shed light on the molecular mechanisms and entail further mechanism studies.Trial Registration: www.chictr.org.cn ChiCTR1900023364. Registered on 24 May 2019. [ABSTRACT FROM AUTHOR]

Numerous studies have provided evidence supporting the significant roles of icariin, in the prevention of multiple chronic diseases like diabetes, liver fibrosis, cardiac fibrosis, renal fibrosis, and pulmonary fibrosis. In particular, Icariside II (ISE II), a prominent flavonoid glycoside derived from Epimedium brevicornum Maxim , the principal metabolite of icariin, has demonstrated noteworthy anti-inflammatory and anti-oxidant properties, along with its ability to protect against lung remodeling. However, the research exploring ISE Ⅱ's application in treating pulmonary fibrosis remains limited. The aim of this study was to assess the therapeutic efficacy of ISE II in models of pulmonary fibrosis, while also investigating its potential mechanisms of action in cell signaling pathways. An in vitro model of pulmonary fibrosis was established by treating NIH-3T3 cells with transforming growth factor-β1 (TGF-β1). Western blot, RT-qPCR, and scratch test were performed to assess the effect of ISE Ⅱ. In addition, a murine model of pulmonary fibrosis was induced by intratracheal instillation of bleomycin, and the therapeutic effect of ISE Ⅱ was tested by orally administering ISE Ⅱ at a dose of 10 mg/kg. Three weeks later, lung function, micro-CT, hydroxyproline content, pathological staining, and cytokines detection of BALF or serum were used to assess the anti-fibrosis effects of ISE Ⅱ. Next, immunofluorescence staining, flow cytometry, and in vivo transcriptomics were used to investigate the underlying mechanisms of action. Our data revealed a significant inhibitory effect of ISE Ⅱ on the upregulation of α-smooth muscle actin (α-SMA) and collagen production induced by TGF-β1 in fibroblasts. Meanwhile, ISE Ⅱ exerted a therapeutic effect against bleomycin-induced pulmonary fibrosis in mice by improving lung function, decreasing collagen deposition, and reducing the expression of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), TGF-β1 and platelet-derived growth factor (PDGF) in serum and bronchoalveolar lavage fluid (BALF). Additionally, ISE Ⅱ treatment effectively attenuated the infiltration of M2 macrophages, concurrently downregulating the expression level of M2 marker genes, such as CD206, arginase-1(Arg-1), and Chitinase-Like Protein 3 (YM-1). Importantly, we observed a statistically significant reduction in the M2 phenotype of interstitial macrophages (IMs). However, the impact of ISE Ⅱ on the M2 polarization of alveolar macrophages (AMs) did not reach statistical significance. Lastly, transcriptome sequencing results suggested that the anti-pulmonary fibrosis effects of ISE Ⅱ may be mediated by the suppression of the WNT/β-catenin signaling pathway, which modulated M2 polarization in macrophages and contributed to the amelioration of pulmonary fibrosis. By immunohistochemical analysis, it was verified that ISE Ⅱ treatment dramatically inhibited the activation of β-catenin in fibrosis murine. Our findings indicated that ISE Ⅱ exerted anti-fibrotic effects by inhibiting pro-fibrotic macrophage polarization. The underlying mechanism of action might be mediated by modulating the WNT/β-catenin signaling pathway to inhibit the M2 program in IMs. [Display omitted] • To our knowledge, this is the first study to estimate the anti-pulmonary fibrosis for ISE II in vitro and in vivo. • ISE II improved pulmonary function and reduced fibrotic biomarkers in a murine model of bleomycin-induced lung fibrosis. • ISE Ⅱ suppressed the infiltration of CD206+ M2-like interstitial macrophages. • Transcriptome sequencing suggested ISE Ⅱ might involve inhibiting the WNT/β-catenin signaling pathway. • This study might yield new insights into ISE II's potential for treating respiratory illnesses. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the regulation of Sophora subprosrate polysaccharide (SSP) on inflammatory response and histone acetylation modification of RAW264.7 cells (mouse mononuclear macrophage cell line) infected with porcine circovirus type 2 (PCV2). We further explored the role of inflammatory response and histone acetylation modification on the basis of the original study. The results showed that SSP decreased the secretion levels of TNF-α and IL-6 and the intracellular iNOS, COX-2 enzyme activities and their mRNA expression levels in PCV2 infected RAW264.7 cells, but increased the level of IL-10 secretion and its mRNA expression. SSP inhibited the phosphorylation levels of proteins of p65, ERK1/2, p38 and c-Jun in RAW264.7 cells infected with PCV2. The activities of HAT and HDAC enzymes and the mRNA expression levels of HAT1 and HDAC1 were increased when the PCV2-infected RAW264.7 cells were treated by SSP. Meanwhile, the expression of acetylation modification of histones both H3 and H4 was obviously inhibited. In conclusion, SSP may reduce the acetylation levels of both H3 and H4 and activate NF-κB/MAPKs/c-Jun signaling pathway by increasing the activity of HADC enzyme and the expression of HDAC mRNA, further inhibiting inflammatory response by regulating the gene expression levels of inflammatory factors. The findings indicated that the molecular mechanism of how traditional Chinese medicine polysaccharide regulates inflammatory signal pathways and inflammatory factors by regulating histone acetylation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The pathogenesis of thromboangiitis obliterans (TAO) has not been fully elucidated until now. Shenfu injection (SFI), a traditional Chinese formula has been widely used clinically for the treatment of cardiovascular diseases for more than two decade. Our previous results first suggested that SFI can cause a significant therapeutic effect on experimental TAO model rats. This experiment was designed to further investigate the protective effect of SFI on VEC damaged by hydrogen peroxide (H 2 O 2 ) oxidative stress in vitro . Meterials and methods The cell viability was evaluated by the MTT assay, the activities of SOD and GSH-PX and the content of MDA in the supernatants of the cultured ECV304 cells were evaluated by a colorimetry method, cell apoptosis was detected by flow cytometry and an AO/EB double staining method. The protein expressions of Bcl2, Bax and caspase-3 were examined by Western blotting. Results When compared with control group, lower survival rate of ECV304 cells was observed in H 2 O 2 group ( p <0.01) ; 20 μl/ml, 30 μl/ml and 40 μl/ml SFI increased the survival rate of ECV304 cells under H 2 O 2 oxidative stress ( p <0.05 and p <0.01). The activities of SOD and GSH-PX were higher and MDA level was lower in H 2 O 2 group than those in control group. These effects of H 2 O 2 on SOD, GSH-PX activities and MDA content were reversed by SFI in concentration-dependent way ( p <0.05 and p <0.01). Flow cytometry and AO–EB double staining discovered that SFI pretreatment inhibited the ECV304 cells apoptosis. The protein expression of caspase3 in 30 μl/ml and 40 μl/ml SFI groups significantly decreased whereas Bcl2 protein expressions in 20 μl/ml, 30 μl/ml and 40 μl/ml SFI groups were higher than H 2 O 2 group, with Bax protein expression much lower than H 2 O 2 group ( p <0.05 and p <0.01). Conclusions Our findings suggest that SFI could prevent the ECV304 cells against H 2 O 2 oxidative-stress by enhancing antioxidant enzyme activities, reducing the membrane lipid peroxidation, as well as upregulating antiapoptotic and downregulating apoptosis protein expressions. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. Aim of the study: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running. Materials and methods: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13mg/kg/d doge, KXS treatment at 175mg/kg/d, 350mg/kg/d and 700mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA. Results: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment. Conclusions: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS. [Copyright &y& Elsevier]

Although considerable advance has been made in diagnosing and treating, asthma is still a serious public health challenge. Traditional Chinese medicine (TCM) is an effective therapy of complementary and alternative medicine. More and more scientific evidences support the use of TCM for asthma treatment, and active ingredients from Chinese medicine plants are becoming a hot issue. To summarize the frontier knowledge on the function and underlying mechanisms of the active ingredients in asthma treatments and provide a fully integrated, reliable reference for exploring innovative treatments for asthma. The cited literature was obtained from the PubMed and CNIK databases (up to September 2020). Experimental studies on the active ingredients of Chinese medicine and their therapeutic mechanisms were identified. The key words used in the literature retrieval were "asthma" and "traditional Chinese medicine" or "Chinese herbal medicine". The literature on the active ingredients was then screened manually. We summarized the effect of these active ingredients on asthma, primarily including the effect through which these ingredients can regulate the immunologic equilibrium mechanism by acting on a number of signalling pathways, such as Notch, JAK-STAT-MAPK, adiponectin-iNOS-NF-κB, PGD2-CRTH2, PI3K/AKT, Keap1-Nrf2/HO-1, T-bet/Gata-3 and Foxp3-RORγt, thereby regulating the progression of asthma. The active ingredients from Chinese medicine have multilevel effects on asthma by regulating the immunologic equilibrium mechanism or signalling pathways, giving them great clinical value. However, the safety and functional mechanism of these ingredients still must be further determined. [Display omitted] ● Active ingredients of TCM are natural products with low toxicity. ● TCM origin from a variety of sources and have potential in anti-inflammatory. ● Biological effects of TCM are mediated by modulation on multiple signaling pathways. ● TCM related anti-inflammatory effect without instigating systemic immunosuppression. [ABSTRACT FROM AUTHOR]

Loki Zupa (LKZP) decoction is one of the herbal prescriptions in traditional Uyghur medicine, which is commonly used for treating airway abnormality. However, underlying pathological mechanism and pathways involved has not been well studied. In this paper, we aim to further confirmed the anti-inflammatory and anti-fibrotic role of LKZP decoction in airway, and uncover the passible mechanism involved via comprehensive quantitative proteomic DIA-MS analysis. Mice asthmatic model was established with sensitizing and challenging with OVA. Lung function, pathological status, and inflammatory cytokines were assessed. Total of nine lung tissues were analyzed using proteomic DIA-MS analysis and 18 lung tissues were subjected to PRM validation. Total of 704 differentially expressed proteins (DEPs) (363 up regulated, 341 down regulated) were quantified in comparison of asthmatic and healthy mice, while 152 DEPs (91 up regulated, 61 down regulated) were quantified in LKZP decoction treated compared to asthmatic mice. Total of 21 proteins were overlapped between three groups. ECM-receptor interaction was significantly enriched and commonly shared between downregulated DEPs in asthma and upregulated DEPs in LKZP decoction treated mice. Total of 20 proteins were subjected to parallel reaction monitoring (PRM) analysis and 16 of which were quantified. At last, two proteins, RMB 10 and COL6A6, were validated with significant difference (P < 0.001) in protein abundance. Conclusions : Our results suggest that attenuated airway inflammation and fibrosis caused by LKZP decoction may associated with ECM-receptor interaction and RMB 10 and COL6A6 may be targeted by LKZP decoction in OVA-induced asthmatic mice. Image 1 [ABSTRACT FROM AUTHOR]

• The fusion quantitative fingerprint contains more information. • The quality control standard is more comprehensive by combining fingerprint with antioxidant activity. • Providing a detection method to control the quality of NAODESHENG on the market. The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency. [ABSTRACT FROM AUTHOR]