Objective:Traditional Chinese medicine (TCM) has been used for the treatment of chronic liver diseases for a long time, with proven safety and efficacy in clinical settings. Previous studies suggest that the therapeutic mechanism of TCM for hepatitis B cirrhosis may involve the gut microbiota. Nevertheless, the causal relationship between the gut microbiota, which is closely linked to TCM, and cirrhosis remains unknown. This study aims to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship between gut microbes and cirrhosis, as well as to elucidate the synergistic mechanisms between botanical drugs and microbiota in treating cirrhosis. Methods:Eight databases were systematically searched through May 2022 to identify clinical studies on TCM for hepatitis B cirrhosis. We analyzed the frequency, properties, flavors, and meridians of Chinese medicinals based on TCM theories and utilized the Apriori algorithm to identify the core botanical drugs for cirrhosis treatment. Cross-database comparison elucidated gut microbes sharing therapeutic targets with these core botanical drugs. MR analysis assessed consistency between gut microbiota causally implicated in cirrhosis and microbiota sharing therapeutic targets with key botanicals. Results:Our findings revealed differences between the Chinese medicinals used for compensated and decompensated cirrhosis, with distinct frequency, dosage, properties, flavors, and meridian based on TCM theory. were the main botanicals. Botanical drugs and gut microbiota target MAPK1, VEGFA, STAT3, AKT1, RELA, JUN, and ESR1 in the treatment of hepatitis B cirrhosis, and their combined use has shown promise for cirrhosis treatment. MR analysis demonstrated a positive correlation between increased ClostridialesvadinBB60 and Ruminococcustorques abundance and heightened cirrhosis risk. In contrast, Eubacteriumruminantium, Lachnospiraceae, Eubacteriumnodatum, RuminococcaceaeNK4A214, Veillonella, and RuminococcaceaeUCG002 associated with reduced cirrhosis risk. Notably, Lachnospiraceae shares key therapeutic targets with core botanicals, which can treat cirrhosis at a causal level. Conclusion:We identified 6 core botanical drugs for managing compensated and decompensated hepatitis B cirrhosis, despite slight prescription differences. The core botanical drugs affected cirrhosis through multiple targets and pathways. The shared biological effects between botanicals and protective gut microbiota offer a potential explanation for the therapeutic benefits of these key herbal components in treating cirrhosis. Elucidating these mechanisms provides crucial insights to inform new drug development and optimize clinical therapy for hepatitis B cirrhosis.

CONTEXT:Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options. OBJECTIVE:This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms. MATERIALS AND METHODS:We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting. RESULTS:ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells. DISCUSSION AND CONCLUSION:THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.

Background:Diabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges Tongmai Jiangtang capsule (TMJT) is commonly used for the treatment of DN, albeit its underlying mechanisms of action are still elusive. Methods:This study retrieved databases to identify the components and collect the targets of TMJT and DN. Target networks were constructed to screen the core components and targets. Samples from the GEO database were utilized to perform analyses of targets and immune cells and obtain significantly differentially expressed core genes (SDECGs). We also selected a machine learning model to screen the feature genes and construct a nomogram. Furthermore, molecular docking, another GEO dataset, and Mendelian randomization (MR) were utilized for preliminary validation. We subsequently clustered the samples based on SDECG expression and consensus clustering and performed analyses between the clusters. Finally, we scored the SDECG score and analyzed the differences between clusters. Results:This study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (, , , , and ) which were used to construct a nomogram. MR analysis indicated a causal link between elevated IL1B levels and an increased risk of DN. Clustering analysis divided DN samples into four groups, among which, C1 and CI were mainly highly expressed and most immune cells were up-regulated. C2 and CII were the opposite. Finally, we found significant differences in SDECG scores between C1 and C2, CI and CII, respectively. Conclusion:TMJT may alleviate DN via core components (e.g. Denudatin B, hancinol, hirudinoidine A) targeting SDECGs (e.g. SRC, EGF, GAPDH), with the involvement of feature genes and modulation of immune and inflammation-related pathways. These findings have potential implications for clinical practice and future investigations.

Background:Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear. Purpose:The purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification. Methods:Search for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets. Results:In RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking. Conclusion:This study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.