Abstract：
Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.
摘要：
斑驳素(CTD)是一种应用广泛的抗癌化合物,但其临床应用主要由于肝毒性而受到限制。人参皂苷Rb1(GRb1)具有潜在的保肝作用。尽管如此，GRb1对CTD诱导的小鼠肝毒性的保护作用和潜在机制尚未研究。本研究旨在通过网络药理学和体内实验阐明GRb1对CTD诱导的肝毒性的影响和机制。网络药理学研究表明，263个靶点是GRb1减轻CTD诱导的肝毒性的主要机制。KEGG富集分析显示75个hub基因主要富集TNF,IL-17和凋亡信号通路。分子对接分析表明GRb1与Akt1、Tnf、Il6、Bcl2和Caspase3。此外,动物实验结果表明,GRb1可以通过抑制Caspase-3、Caspase-8、Bcl-2/Bax蛋白的表达来改善CTD诱导的肝毒性,GRP78,ATF6,ATF4,CHOP,IRE1α和PERK。这项研究揭示了GRb1通过抑制细胞凋亡和内质网应激（ERS）抵抗CTD诱导的肝毒性的机制，这可能为GRb1在治疗CTD诱导的肝毒性中的潜在用途提供科学依据。
