Exocarpium Citri Grandis Attenuates Lipopolysaccharide-Induced Acute Liver Injury Through Dual Suppression of Data for Inflammatory Response and Apoptotic Pathways

This study investigates Exocarpium Citri Grandis (ECG)'s therapeutic effects on LPS-induced acute liver injury (ALI) through network pharmacology and murine models. ECG treatment significantly reduced serum AST/ALT levels and alleviated hepatic damage in mice, as confirmed by histopathological analysis. The herbal extract demonstrated dual anti-inflammatory and anti-cell death mechanisms by downregulating pro-inflammatory cytokines (IL-6, IL-1β, TNFα) through qPCR analysis, while simultaneously modulating apoptosis and ferroptosis markers. Network pharmacology revealed ECG's multi-target action on critical pathways involving inflammation regulation and cell survival. Molecular docking simulations validated interactions between ECG's bioactive components and key apoptotic/inflammatory regulators. These findings position ECG as a promising natural therapeutic for ALI treatment, combining traditional medicinal use with evidence-based mechanisms of action. The integrated approach confirms ECG's potential to mitigate liver injury through coordinated modulation of inflammatory responses and programmed cell death pathways, warranting further clinical exploration of this traditional Chinese medicine for managing severe hepatic conditions.

本研究借助网络药理学与小鼠模型，探究化橘红（Exocarpium Citri Grandis, ECG）对脂多糖（lipopolysaccharide, LPS）诱导的急性肝损伤（acute liver injury, ALI）的治疗效应。给药干预后，小鼠血清中天冬氨酸氨基转移酶/丙氨酸氨基转移酶（AST/ALT）水平显著降低，肝脏损伤得以缓解，该结论经组织病理学分析得到验证。该中药提取物可通过下调促炎细胞因子（IL-6、IL-1β、TNF-α）发挥抗炎与抗细胞死亡的双重作用机制，此结果经实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qPCR）分析证实；与此同时，其可调控细胞凋亡与铁死亡（ferroptosis）相关标志物的表达水平。网络药理学分析揭示，化橘红可通过多靶点作用于炎症调控与细胞存活相关的关键通路。分子对接模拟验证了化橘红活性成分与关键凋亡/炎症调控因子之间的相互作用。本研究结果表明，化橘红是一种极具潜力的急性肝损伤天然治疗药物，其将传统药用应用与循证作用机制相结合。本研究采用的整合研究策略证实，化橘红可通过协同调控炎症反应与程序性细胞死亡通路减轻肝脏损伤，为这款中药用于重症肝病的临床管理提供了依据，有待开展进一步的临床探索。