Xu Xinyi, Liu Jin, Li Xue, Feng QuanSheng, Su Yue
College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Heliyon. 2024 Aug 14;10(16):e36267. doi: 10.1016/j.heliyon.2024.e36267. eCollection 2024 Aug 30.
Chronic hepatitis B infection (CHB) is a major risk factor for the development of hepatocellular carcinoma (HCC) globally and continues to pose a significant global health challenge. Jiawei Yinchenhao decoction (JWYCH) is a modified version of Yinchenhao decoction (YCHD), which is widely used to treat liver diseases including icteric hepatitis, cholelithiasis, and hepatic ascites. However, the effectiveness and underlying mechanism of JWYCH on CHB are still unclear. This study aimed to investigate the impact of JWYCH on CHB and explore the underlying mechanism via network pharmacology and metabolomics. C57BL/6 mice were administered rAAV-HBV1.3 via hydrodynamic injection (HDI) to establish the CHB model. The infected mice were orally administered JWYCH for 4 weeks. HBsAg, HBeAg, HBV DNA, the serum liver function index, and histopathology were detected. In addition, network pharmacology was used to investigate potential targets, whereas untargeted metabolomics analysis was employed to explore the hepatic metabolic changes in JWYCH in CHB mice and identify relevant biomarkers and metabolic pathways. JWYCH was able to reduce HBeAg levels and improve liver pathological changes in mice with CHB. Additionally, metabolomics analysis indicated that JWYCH can influence 105 metabolites, including pipecolic acid, alpha-terpinene, adenosine, and L-phenylalanine, among others. Bile acid metabolism, arachidonic acid metabolism, and retinol metabolism are suggested to be potential targets of JWYCH in CHB. In conclusion, JWYCH demonstrated a hepatoprotective effect on a mouse model of CHB, suggesting a potential alternative therapeutic strategy for CHB. The effect of JWYCH is associated mainly with regulating the metabolism of bile acid, arachidonic acid, and retinol. These differentially abundant metabolites may serve as potential biomarkers and therapeutic targets for CHB.
慢性乙型肝炎感染（CHB）是全球肝细胞癌（HCC）发生的主要危险因素，并且仍然是一项重大的全球健康挑战。加味茵陈蒿汤（JWYCH）是茵陈蒿汤（YCHD）的改良方，广泛用于治疗包括黄疸型肝炎、胆结石和肝腹水在内的肝脏疾病。然而，JWYCH对CHB的有效性及潜在机制仍不清楚。本研究旨在探讨JWYCH对CHB的影响，并通过网络药理学和代谢组学探索其潜在机制。通过尾静脉高压注射（HDI）将重组腺相关病毒-HBV1.3（rAAV-HBV1.3）注射到C57BL/6小鼠体内以建立CHB模型。给感染的小鼠口服JWYCH 4周。检测乙肝表面抗原（HBsAg）、乙肝e抗原（HBeAg）、乙肝病毒DNA（HBV DNA）、血清肝功能指标及组织病理学。此外，采用网络药理学研究潜在靶点，同时采用非靶向代谢组学分析探索JWYCH对CHB小鼠肝脏代谢变化的影响，并鉴定相关生物标志物和代谢途径。JWYCH能够降低CHB小鼠的HBeAg水平并改善肝脏病理变化。此外，代谢组学分析表明JWYCH可影响105种代谢物，包括哌啶酸、α-萜品烯、腺苷和L-苯丙氨酸等。胆汁酸代谢、花生四烯酸代谢和视黄醇代谢被认为是JWYCH在CHB中的潜在靶点。总之，JWYCH对CHB小鼠模型具有肝脏保护作用，提示其可能是CHB的一种潜在替代治疗策略。JWYCH的作用主要与调节胆汁酸、花生四烯酸和视黄醇的代谢有关。这些差异丰富的代谢物可能作为CHB的潜在生物标志物和治疗靶点。
