School of Basic Medicine and Clinical Pharmacology, China Pharmaceutical University, Nanjing, 211100, China.
School of Basic Medicine and Clinical Pharmacology, China Pharmaceutical University, Nanjing, 211100, China.
J Ethnopharmacol. 2020 Aug 10;258:112917. doi: 10.1016/j.jep.2020.112917. Epub 2020 Apr 30.
Oroxyloside is a natural flavonoid isolated from Scutellaria baicalensis Georgi (Lamiaceae) which is a Chinese herb widely used for liver diseases. However, its mechanisms on protecting against drug induced liver injury has not been investigated yet.
To investigate the protecting effects and the primary mechanisms of oroxyloside on acetaminophen (APAP)-induced liver injury.
After a 12 h fasting period with free access to water, C57BL/6 mice were injected with APAP (300 mg/kg) intragastrically (i.g.) and 1 h later with oroxyloside (100 mg/kg, i.g.). When mice sacrificed, blood samples were collected from fundus venous plexus and liver tissues were collected. In addition, cells were incubated with 10 mM APAP alone and 10 mM APAP combined with 100 μM oroxyloside for 24 h. ELISA, TUNEL assay, qRT-PCR et al. were used to assess the effect of oroxyloside on ameliorating APAP-induced hepatotoxicity in vitro and in vivo. Western bolt and immunohistochemistry were used in the signaling pathway analysis.
Oroxyloside administration significantly decreased the accumulations of CYP2E1, CYP1A2, IL-6, IL-1β, ALT and AST induced by APAP in vivo. In addition, oroxyloside inhibited the APAP-induced JNK related apoptosis by enhancing the antioxidant defenses, reversing ER-stress and keeping the mito-balance of liver cells in vivo and in vitro. Furthermore, oroxyloside protected the liver cells from necroptosis by affecting JNK pathway.
Oroxyloside acted as a protective agent against APAP-induced liver injury through inhibiting JNK-related apoptosis and necroptosis.
梓醇是从黄芩（唇形科）中分离出来的一种天然类黄酮，黄芩是一种中国草药，广泛用于治疗肝脏疾病。然而，其对药物性肝损伤的保护机制尚未得到研究。
研究梓醇对乙酰氨基酚（APAP）诱导的肝损伤的保护作用及其主要机制。
禁食 12 小时后，C57BL/6 小鼠经口（ig）给予 APAP（300mg/kg），1 小时后给予梓醇（100mg/kg，ig）。当小鼠被处死时，从眼底静脉丛采集血液样本，并采集肝组织。此外，细胞单独孵育 10mM APAP 和 10mM APAP 联合 100μM 梓醇 24 小时。ELISA、TUNEL 检测、qRT-PCR 等用于评估梓醇对改善体内外 APAP 诱导的肝毒性的作用。Western bolt 和免疫组织化学用于信号通路分析。
梓醇给药可显著降低 APAP 在体内诱导的 CYP2E1、CYP1A2、IL-6、IL-1β、ALT 和 AST 的积累。此外，梓醇通过增强抗氧化防御、逆转内质网应激和维持肝细胞线粒体平衡，抑制 APAP 诱导的 JNK 相关细胞凋亡，在体内和体外均发挥作用。此外，梓醇通过影响 JNK 通路来保护肝细胞免于坏死性凋亡。
梓醇通过抑制 JNK 相关的细胞凋亡和坏死性凋亡，作为一种对抗 APAP 诱导的肝损伤的保护剂。
