Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.

Background: Extensive research has demonstrated that the gut microbiota plays a critical role in maintaining homeostasis and promoting overall human health. However, the pharmacological mechanisms and functional roles of gut microbiota metabolites remain insufficiently understood. This study employs a network pharmacology approach to elucidate the metabolic transformation processes of gut microbiota metabolites and their molecular mechanisms in the pathogenesis of insulin resistance (IR), aiming to uncover the complex interactions among gut microbiota, metabolites, and therapeutic targets.Methods: Gut microbiota metabolites and their corresponding target genes were retrieved from the gutMGene database. Potential targets of the metabolites were predicted using the SEA and STP databases. Disease-related targets for insulin resistance were collected from the GeneCards, DisGeNET, and OMIM databases. Core targets were identified via a protein–protein interaction (PPI) network, followed by comprehensive GO and KEGG enrichment analyses. Finally, a network illustrating the relationship among microbiota-substrate-metabolite-target was established.Results: Thirteen overlapping targets between the gut microbiota and insulin resistance were identified, among which IL6, JUN, and PPARG were recognized as hub genes. The MSMT (microbiota-substrate-metabolite-target) network revealed that these three hub genes exert therapeutic effects through 10 gut microbiota metabolites, 10 substrates, and 21 microbial species. KEGG pathway analysis indicated that the IL-17, Toll-like receptor, HIF-1, NOD-like receptor, TNF, and VEGF signaling pathways are the primary pathways involved in the pathogenesis of IR.Conclusion: Gut microbiota metabolites may exert therapeutic effects on insulin resistance primarily through the targets IL6, JUN, and PPARG. The regulatory mechanisms are likely associated with several key signaling pathways, including the IL-17, Toll-like receptor and HIF-1, pathways. These three pathways collectively form an interconnected inflammation-metabolism-hypoxia network. Targeting key nodes within this network—such as the IL-17 receptor, TLR4, or HIF-1α—may offer a multidimensional therapeutic strategy for insulin resistance (IR) and its associated complications.

Objective: The objective of this study was to investigate the global research trends in herbal medicine for the treatment of cardiovascular disease (CVD) from 2000 to 2023. A bibliometric approach was employed to analyze international collaborations, knowledge structures, emerging trends, and research frontiers. Method: The Web of Science (WOS) core collection was utilized as the database, employing the search formula (((TS = (traditional Chinese medicine)) OR TS = (Chinese herbal medicinal ingredient)) OR TS = (Chinese herbal medicinal constituent)) AND TS = (cardiovascular disease) to conduct the search. The search period spanned from January 1, 2000, to February 14, 2023, and the literature type included articles and reviews. Results: A total of 1478 papers were included in the analysis after searching the WOS database and excluding conference proceedings, news articles, retractions, editorials, and letters. China demonstrated the highest number of publications, followed by the United States and Taiwan (China). The institution with the highest publications was the Chinese Academy of Medical Sciences. China, the United States, and India were the main countries involved in research in this field, and there was significant collaboration among them. The hotspots related to herbal components for treating cardiovascular diseases from 2000 to 2023 included systematic reviews, ischemic reperfusion injury, global burden, type 2 diabetes, and protection. Conclusion: This paper provides a reference for the future development of herbal research in cardiovascular aspects by revealing the current status, hotspots, and trends of global herbal research in cardiovascular factors over more than 20 years. Identification of potential collaborators and institutions can assist researchers in exploring new directions for future research and discovering new perspectives for potential collaborations in this field.