Dong Wenjie, Mou Yao, Li Qiuyu, Li Min, Su Hao, Jiang Longyang, Zhou Jie, Tu Kun, Yang Xuping, Huang Yuexi, Xu Changjing, Zhang Liaoyun, Huang Yilan
Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
School of Pharmacy, Southwest Medical University, Luzhou, China.
Front Pharmacol. 2025 Mar 26;16:1508290. doi: 10.3389/fphar.2025.1508290. eCollection 2025.
Drug-induced liver injury (DILI) is the most common cause of acute liver injury. Anoectochilus roxburghii (Wall.) Lindl. (AR) and its polysaccharide fractions (ARPs) have been shown to have effective therapeutic effects with minimal side effects on a wide range of diseases including hepatopathy. This study aims to determine the therapeutic effects of ARPs on acetaminophen (APAP)-induced liver injury and to explore the mechanistic pathways involved.
C57BL/6J male mice at 8 weeks were used to construct a model of APAP-induced liver injury. The acute hepatic injury was induced by oral administration of APAP (300 mg/kg) before 16 h fasting. For therapeutic experiment, mice were gavaged with the water extract of AR (AR.WE) or the purified ARPs before and after APAP administration. Biochemical analyses, ELISA analyses, H&E staining, RT-PCR, and Quantitative proteomic analysis were used to investigate the effects and mechanisms of AR on DILI.
Both AR.WE. and the purified ARPs treatment reduced APAP-induced liver injury, decreased hepatic glutathione and TNF-α levels, alleviated oxidative stress and inflammation. Quantitative proteomic analysis revealed that ARPs downregulated the protein levels involved in apoptosis, inflammation, oxidative stress, necroptosis, while upregulated the protein levels involved in autophagy. These protective effects of ARPs are possibly related to the downregulation of vATPase activity and thus participating in the autophagic process and ferroptosis.
ARPs can protect mice against APAP-induced liver injury, alleviate oxidative stress and inflammation. Our study reveals a potential therapeutic effect for ARPs in protecting APAP-induced liver injury.
药物性肝损伤（DILI）是急性肝损伤最常见的原因。金线莲（Anoectochilus roxburghii (Wall.) Lindl.，AR）及其多糖组分（ARPs）已被证明对包括肝病在内的多种疾病具有有效的治疗作用且副作用极小。本研究旨在确定ARPs对乙酰氨基酚（APAP）诱导的肝损伤的治疗效果，并探索其中涉及的机制途径。
选用8周龄的C57BL/6J雄性小鼠构建APAP诱导的肝损伤模型。在禁食16小时前口服给予APAP（300 mg/kg）诱导急性肝损伤。在治疗实验中，在给予APAP前后分别给小鼠灌胃AR的水提取物（AR.WE）或纯化的ARPs。采用生化分析、ELISA分析、苏木精-伊红（H&E）染色、逆转录-聚合酶链反应（RT-PCR）和定量蛋白质组学分析来研究AR对DILI的作用及机制。
AR.WE和纯化的ARPs处理均减轻了APAP诱导的肝损伤，降低了肝脏谷胱甘肽和肿瘤坏死因子-α（TNF-α）水平，减轻了氧化应激和炎症。定量蛋白质组学分析显示，ARPs下调了参与细胞凋亡、炎症、氧化应激、坏死性凋亡的蛋白质水平，而上调了参与自噬的蛋白质水平。ARPs的这些保护作用可能与下调液泡型ATP酶（vATPase）活性从而参与自噬过程和铁死亡有关。
ARPs可保护小鼠免受APAP诱导的肝损伤，减轻氧化应激和炎症。我们的研究揭示了ARPs在保护APAP诱导的肝损伤方面的潜在治疗作用。
