Shin Mi-Rae, Lee Se Hui, Roh Seong-Soo
Department of Herbology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Republic of Korea.
Evid Based Complement Alternat Med. 2022 Jan 28;2022:7904845. doi: 10.1155/2022/7904845. eCollection 2022.
Acute liver injury (ALI) can occur for various reasons by induced inflammation and apoptosis of liver cells including hepatocytes, Kupffer cells, and hepatic stellate cells. Thioacetamide (TAA), which is a classic hepatotoxin, causes oxidative stress, membrane damage, and accumulation of lipid droplets and subsequently provokes consecutive liver injury. In the current study, we tested whether Paeoniae Radix Alba (PR) could alleviate TAA-induced ALI.
Thirty-five male rats were equally separated into five groups. The first group was the normal group, which received distilled water only. The remaining four groups received intraperitoneal TAA (200 mg/kg) for 3 days to induce ALI. The four groups were divided into the control group (no treatment), silymarin-treated, 100 mg/kg PR-treated, and 200 mg/kg PR-treated. The efficacy of PR against hepatotoxicity was evaluated in terms of the serum biochemical index and protein expression associated with inflammation and apoptosis. Moreover, the dissected livers were analyzed by hematoxylin and eosin stain.
PR alleviated liver dysfunction as evidenced by decreased levels of aspartate aminotransferase, alanine aminotransferase, and ammonia. Phosphorylated AMP-activated protein kinase (AMPK) and Sirtuin 1 (Sirt1) levels were obviously decreased in the TAA control group, whereas PR reversed these changes. PR also prevented deteriorative effects through inhibition of inflammation and apoptosis via nuclear transcription factor-kappa Bp65 (NF-Bp65) inactivation. Moreover, we found that the hepatoprotective effect of PR pretreatment was mediated by restoration of histopathological changes.
PR efficiently blocked both the inflammatory response and apoptosis through activating the AMPK/Sirt1/NF-Bp65 pathway. Therefore, PR is considered a potential therapeutic agent against ALI.
急性肝损伤（ALI）可由多种原因引起，包括肝细胞、库普弗细胞和肝星状细胞的炎症和凋亡。硫代乙酰胺（TAA）是一种经典的肝毒素，可引起氧化应激、膜损伤和脂滴积累，进而引发持续性肝损伤。在本研究中，我们测试了白芍（PR）是否能减轻TAA诱导的ALI。
35只雄性大鼠平均分为五组。第一组为正常组，仅给予蒸馏水。其余四组腹腔注射TAA（200mg/kg）3天以诱导ALI。这四组分为对照组（未治疗）、水飞蓟宾治疗组、100mg/kg PR治疗组和200mg/kg PR治疗组。通过血清生化指标以及与炎症和凋亡相关的蛋白表达来评估PR对肝毒性的疗效。此外，对解剖后的肝脏进行苏木精和伊红染色分析。
PR减轻了肝功能障碍，表现为天冬氨酸转氨酶、丙氨酸转氨酶和氨水平降低。TAA对照组中磷酸化的AMP激活蛋白激酶（AMPK）和沉默信息调节因子1（Sirt1）水平明显降低，而PR逆转了这些变化。PR还通过使核转录因子-κB p65（NF-κB p65）失活来抑制炎症和凋亡，从而防止恶化效应。此外，我们发现PR预处理的肝保护作用是通过恢复组织病理学变化来介导的。
PR通过激活AMPK/Sirt1/NF-κB p65途径有效阻断炎症反应和凋亡。因此，PR被认为是一种治疗ALI的潜在药物。
