Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.

The gut microbiota, as an important factor affecting host health, plays a significant role in the occurrence and development of diabetes mellitus (DM), and the mechanism may be related to excessive endotoxins, altered short-chain fatty acids (SCFAs), and disordered bile acid metabolism. Traditional Chinese medicine (TCM) has a long history of treating DM, but its mechanism is not very clear. Recent research has suggested that Chinese herbal medicine can improve glucose metabolism by remodeling the gut microbiota, which opens new avenues for further research on hypoglycemic mechanisms. This review presents the recent progress of Chinese herbs, herbal extracts, and herbal compound preparations in treating DM through regulating the gut microbiota and summarizes the main mechanisms involved, namely, anti-inflammatory and antioxidative effects, protecting the intestinal barrier and inhibiting lipotoxicity. In addition, some suggestions for improvement are also proposed.

Recent studies have confirmed that increased intestinal permeability and gut‐origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti‐inflammatory and gut microbiota‐modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin‐1, occludin, and zonula occludens (ZO‐1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin‐1β (IL‐1β), IL‐6, and tumour necrosis factor‐α (TNF‐α) in intestinal tissue and that the anti‐inflammatory effects involved the TLR‐4/TRIF and TNFR‐1/NF‐κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS‐producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate‐producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

Background. Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. Methods. The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein‐protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan‐Meier Plotter online tool. Results. A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease‐associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. Conclusions. This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.

Background: Type 2 diabetes mellitus (T2DM) is a subtype of diabetes mellitus characterized by progressive dysfunction of β-cell insulin secretion and insulin resistance. Jīn-Guì Shèn-Qì Wán (JGSQW) has for many years been widely used in clinical practice as a treatment for T2DM. However, its effect remains unknown.Objectives: This study aims to summarize the clinical evidence of the effect of JGSQW on glucose and lipid metabolism in T2DM and the potential mechanisms underlying this effect.Methods: Six databases were searched without language or publication status restrictions. Data were extracted to a predefined template for synthesis.Results: Fourteen studies with 1586 participants were included in this meta-analysis. All 14 studies were judged to be at high risk of bias. JGSQW is safe for T2DM patients. Pooled results indicated that combination treatment results in a reduction in glycated hemoglobin (HbA1c) (mean difference (MD) −0.49%; 95% CI −0.67 to −0.31), fasting blood glucose (FBG) (MD −0.84; 95% CI −1.19 to −0.49), and 2-hour postprandial glucose 2hBG (MD −1.38; 95% CI −1.60 to −1.16). No significant difference in glucose metabolism was observed between JGSQW and hypoglycemic agents. The available evidence was insufficient to determine the effects on lipid metabolism. Sensitivity analyses indicated that these results were robust.Conclusion: By combining the available evidence, we found that JGSQW is safe for T2DM patients. Compared with hypoglycemic agents alone, combination treatment with JGSQW enhances the effect on glucose metabolism in patients with T2DM. We found no difference in the efficacy of JGSQW alone compared to hypoglycemic agents alone. In terms of lipid metabolism, the current evidence is insufficient and too inconsistent for us to draw firm conclusions, so further studies are needed.