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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]

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]