Tang Chao-Ling, Ma Ning, Sun Wan-Ying, Wang Wei, Zhu Li-Peng, Wang Rui-Qi, Liu Jie-Yan, Zhang Xiao-Po
Department of Pharmacy, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China.
Reproductive Medicine Center, Women and Children Medical Center of Hainan Province, Haikou 571000, China.
Evid Based Complement Alternat Med. 2022 Aug 22;2022:1375864. doi: 10.1155/2022/1375864. eCollection 2022.
Acetaminophen-related hepatic injury (ARHI) is a kind of acute hepatic injury caused by overdosing acetaminophen, which is mainly related to toxic metabolite production, oxidative stress, and mitochondrial dysfunction. The extract of (Lour.) Merr. (PSM) has the abilities of anti-inflammatory, antivirus, and antioxidation. Research studies showed that PSM could improve acute or chronic hepatic injury, while the mechanism of which is still indistinct.
Here, the authors applied the approach based on serum metabonomics combined with network pharmacology to study the protection of PSM on ARHI rats.
10 serum potential biomarkers were found to be closely related to ARHI by metabonomics, while 3 compounds (L-ascorbyl 2,6-dipalmitate, squalene, and tributyl O-acetylcitrate) and 3 targets (NOS2, MAOB, and PDE3A) were found that might be the potential active components and active site of PSM on treating ARHI by network pharmacology analysis. Furthermore, molecular biology strategy was performed to validate whether iNOS/NF-B signaling pathway is the potential mechanism of PSM treating ARHI.
This study indicated that PSM could ameliorate ARHI by iNOS/NF-B signaling pathway. During ARHI treatment by PSM, L-ascorbyl 2, 6-dipalmitate, squalene, and tributyl O-acetylcitrate might be the potential active components, while the possible active site might be NOS2, MAOB, and PDE3A.
对乙酰氨基酚相关肝损伤(ARHI)是一种因过量服用对乙酰氨基酚引起的急性肝损伤,主要与毒性代谢产物生成、氧化应激和线粒体功能障碍有关。积雪草提取物(PSM)具有抗炎、抗病毒和抗氧化能力。研究表明PSM可改善急性或慢性肝损伤,但其机制仍不明确。
在此,作者应用基于血清代谢组学结合网络药理学的方法来研究PSM对ARHI大鼠的保护作用。
通过代谢组学发现10种血清潜在生物标志物与ARHI密切相关,而通过网络药理学分析发现3种化合物(L-抗坏血酸2,6-二棕榈酸酯、角鲨烯和三丁基O-乙酰柠檬酸酯)和3个靶点(NOS2、MAOB和PDE3A)可能是PSM治疗ARHI的潜在活性成分和活性位点。此外,采用分子生物学策略来验证iNOS/NF-κB信号通路是否是PSM治疗ARHI的潜在机制。
本研究表明PSM可通过iNOS/NF-κB信号通路改善ARHI。在PSM治疗ARHI过程中,L-抗坏血酸2,6-二棕榈酸酯、角鲨烯和三丁基O-乙酰柠檬酸酯可能是潜在活性成分,而可能的活性位点可能是NOS2、MAOB和PDE3A。