Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea.
Alka Hospital Private Limited, Jwalakhel, Kathmandu 446010, Nepal.
Int J Mol Sci. 2023 Jul 9;24(14):11255. doi: 10.3390/ijms241411255.
Liver injury can be acute or chronic, resulting from a variety of factors, including viral hepatitis, drug overdose, idiosyncratic drug reaction, or toxins, while the progression of pathogenesis in the liver rises due to the involvement of numerous cytokines and growth factor mediators. Thus, the identification of more effective biomarker-based active phytochemicals isolated from medicinal plants is a promising strategy to protect against CCl-induced liver injury. L. (VE) and (CE) are well-known medicinal plants that possess anti-inflammatory and antioxidant properties. However, synergism between the two has not previously been studied. Here, we investigated the synergistic effects of a L. (VE) leaf, (CE) extract combination (VCEC) against CCl-induced liver injury. Acute liver injury was induced by a single intraperitoneal administration of CCl (1 mL/kg). VCEC was administered orally for three consecutive days at various concentrations (100 and 200 mg/kg) prior to CCl injection. The extent of liver injury and the protective effects of VCEC were evaluated by biochemical analysis and histopathological studies. Oxidative stress was evaluated by measuring malondialdehyde (MDA) and glutathione (GSH) levels and Western blotting. VCEC treatment significantly reduced serum transaminase levels (AST and ALT), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS). CCl- induced apoptosis was inhibited by VCEC treatment by reducing cleaved caspase-3 and Bcl2-associated X protein (Bax). VCEC-treated mice significantly restored cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expression in CCl4-treated mice. In addition, VCEC downregulated overexpression of proinflammatory cytokines and hepatic nuclear factor kappa B (NF-κB) and inhibited CCl4-mediated apoptosis. Collectively, VCEC exhibited synergistic protective effects against liver injury through its antioxidant, anti-inflammatory, and antiapoptotic ability against oxidative stress, inflammation, and apoptosis. Therefore, VCEC appears promising as a potential therapeutic agent for CCl-induced acute liver injury in mice.
肝损伤可分为急性或慢性，由多种因素引起，包括病毒性肝炎、药物过量、特异质药物反应或毒素，而发病机制在肝脏中的进展则由于涉及众多细胞因子和生长因子介质而升高。因此，鉴定更多有效的基于生物标志物的活性植物化合物，这些化合物是从药用植物中分离出来的，是一种预防 CCl 诱导的肝损伤的有前途的策略。L.（VE）和（CE）是众所周知的药用植物，具有抗炎和抗氧化特性。然而，两者之间的协同作用以前没有被研究过。在这里，我们研究了 L.（VE）叶和（CE）提取物组合（VCEC）对 CCl 诱导的肝损伤的协同作用。通过单次腹腔注射 CCl（1mL/kg）诱导急性肝损伤。VCEC 在 CCl 注射前连续三天以不同浓度（100 和 200mg/kg）口服给药。通过生化分析和组织病理学研究评估肝损伤的程度和 VCEC 的保护作用。通过测量丙二醛（MDA）和谷胱甘肽（GSH）水平和 Western 印迹评估氧化应激。VCEC 处理显著降低血清转氨酶水平（AST 和 ALT）、肿瘤坏死因子-α（TNF-α）和活性氧（ROS）。VCEC 处理通过降低裂解半胱天冬酶-3 和 Bcl2 相关 X 蛋白（Bax）抑制 CCl 诱导的细胞凋亡。VCEC 处理的小鼠显著恢复了 CCl4 处理的小鼠中细胞色素 P450 2E1、核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）的表达。此外，VCEC 下调了促炎细胞因子和肝核因子 kappa B（NF-κB）的过度表达，并抑制了 CCl4 介导的细胞凋亡。总之，VCEC 通过其抗氧化、抗炎和抗细胞凋亡能力对氧化应激、炎症和细胞凋亡发挥协同保护作用，对肝损伤具有协同保护作用。因此，VCEC 似乎有望成为治疗 CCl 诱导的小鼠急性肝损伤的潜在治疗剂。
