Ginsenoside Re

YangxinDingji Capsule (YXDJ), derived from the classical Zhigancao Decoction, is widely applied in clinical practice to treat arrhythmias, alleviate myocardial injury, and protect cardiac function; however, its underlying protective mechanism remains unclear. In this study, we investigated the mechanisms underlying the cardioprotective effects of YXDJ using an integrative approach that combined metabolomics and network pharmacology. A rat model of arrhythmia was established using isoproterenol (ISO) induction. The concentrations of five core components in YXDJ, namely Liquiritigenin, Liquiritin, Rhmannioside D, Ginsenoside Re, and Ginsenoside Rg1, were quantified using HPLC-MS/MS. Metabolomic analysis based on UPLC-Q-Exactive-Orbitrap-MS was performed to identify key differential metabolites and their associated pathways. Potential targets of YXDJ core components were predicted through network pharmacology, molecular docking, and molecular dynamics simulations, and subsequently validated in vivo. The results demonstrated that the five core components of YXDJ exhibited excellent linearity within their respective concentration ranges (R² ≥ 0.9992), along with good stability, repeatability, and recovery. Metabolomic analysis indicated that YXDJ exerted cardioprotective effects by modulating differential metabolites such as 1-Methylhistidine, sphinganine, and phytosphingosine, and by participating in pathways including Histidine metabolism and Sphingolipid metabolism. Network pharmacology, molecular docking, and molecular dynamics simulations further identified two stable complexes with high binding affinities, namely Liquiritin-SRC and Liquiritin-PTGS2. Consistently, in vivo experiments confirmed that YXDJ alleviated arrhythmia-induced myocardial injury through SRC and PTGS2, thereby exerting significant cardioprotective effects. This study suggests that the core components of YXDJ, exemplified by liquiritigenin, exert cardioprotective effects against arrhythmias by modulating SRC, PTGS2, and associated metabolic profiles. This offers new insights and a scientific basis for studying YXDJ's mechanism of action and its clinical application.

A Parkinson's disease (PD) model was established using male C57BL/6 mice administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), through which the neuroprotective effect of Ginsenoside Re (G-Re) was investigated. Although G-Re has demonstrated beneficial effects in MPTP-treated mice, its in vivo activity and the mechanisms underlying its therapeutic potential in PD remain insufficiently understood. In this study, microbiomics and metabolomics analyses were comprehensively employed to investigate gut microbial and metabolic changes in MPTP-induced mice following G-Re intervention, with the aim of elucidating G-Re's mechanisms of action in PD. G-Re administration was found to alleviate dyskinesia, attenuate dopaminergic neuronal loss, reduce alpha-synuclein aggregation, and enhance antioxidant defenses in MPTP-treated mice. Notably, G-Re significantly increased the relative abundance of Bifidobacterium, Clostridium, and Prevotella while decreasing the relative abundance of Akkermansia, Sutterella, and Allobaculum, thereby contributing to the restoration of gut microbiota composition. Non-targeted metabolomics revealed that G-Re exerted neuroprotective effects by modulating disruptions in the arachidonic acid, sphingolipid, and linoleic acid metabolic pathways, as well as pathways related to the biosynthesis of unsaturated fatty acids. Correlation analyses further demonstrated a significant association between specific gut microbes and the sphingolipid metabolic pathway. In addition, G-Re was found to inhibit pro-apoptotic proteins such as Bax and caspase-3 within the sphingolipid pathway while promoting the activity of anti-apoptotic proteins. Collectively, these findings provide both a scientific and theoretical basis supporting the therapeutic potential of G-Re in the treatment of PD.