Department of Pharmacology and New Drug Development Institute, Chonbuk National University Medical School, Jeonju, Chonbuk 561-180, Korea.
Non-Clinical Evaluation Center, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Chonbuk 561-180, Korea.
Nutrients. 2019 Feb 12;11(2):382. doi: 10.3390/nu11020382.
This study aimed to characterize the protective effects of R. verniciflua extract (ILF-R) and E. ulmoides extract (ILF-E), the combination called ILF-RE, against chronic CCl₄-induced liver oxidative injury in rats, as well as to investigate the mechanism underlying hepatoprotection by ILF-RE against CCl₄-induced hepatic dysfunction. Chronic hepatic stress was induced via intraperitoneal (IP) administration of a mixture of CCl₄ (0.2 mL/100 g body weight) and olive oil [1:1(v/v)] twice a week for 4 weeks to rats. ILF-RE was administered orally at 40, 80, and 120 mg/kg to rats for 4 weeks. Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and lipid peroxidation assays were performed, and total triglyceride, cholesterol, and LDL-cholesterol levels were quantified. Furthermore, ER stress and lipogenesis-related gene expression including sterol regulatory element-binding transcription factor 1 (SREBP-1), fatty acid synthase (FAS), and P-AMPK were assessed. ILF-RE markedly protected against liver damage by inhibiting oxidative stress and increasing antioxidant enzyme activity including glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Furthermore, hepatic dyslipidemia was regulated after ILF-RE administration. Moreover, hepatic lipid accumulation and its associated lipogenic genes, including those encoding SREBP-1 and FAS, were regulated after ILF-RE administration. This was accompanied by regulation of ER stress response signaling, suggesting a mechanism underlying ILF-RE-mediated hepatoprotection against lipid accumulation. The present results indicate that ILF-RE exerts hepatoprotective effects against chronic CCl₄-induced dysfunction by suppressing hepatic oxidative stress and lipogenesis, suggesting that ILF-RE is a potential preventive/therapeutic natural product in treating hepatoxicity and associated dysfunction.
本研究旨在探讨瑞香狼毒（ILF-R）和榆树（ILF-E）提取物，即 ILF-RE 混合物对慢性 CCl4 诱导的大鼠肝氧化损伤的保护作用，并探讨其对 CCl4 诱导的肝损伤的肝保护作用机制。通过每周两次腹膜内（IP）给予 CCl4（0.2 mL/100 g 体重）和橄榄油[1:1（v/v）]混合物，诱导慢性肝应激，持续 4 周。ILF-RE 以 40、80 和 120 mg/kg 的剂量口服给予大鼠 4 周。进行丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、γ-谷氨酰转肽酶（GGT）和脂质过氧化测定，并定量总三酰甘油、胆固醇和 LDL-胆固醇水平。此外，评估内质网应激和脂生成相关基因表达，包括固醇调节元件结合转录因子 1（SREBP-1）、脂肪酸合酶（FAS）和 P-AMPK。ILF-RE 通过抑制氧化应激和增加抗氧化酶活性（包括谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶），显著保护肝脏免受损伤。此外，ILF-RE 给药后调节肝内血脂异常。此外，ILF-RE 给药后调节肝内脂质蓄积及其相关的脂生成基因，包括编码 SREBP-1 和 FAS 的基因。这伴随着内质网应激反应信号的调节，提示 ILF-RE 介导的抗脂质蓄积肝保护作用的机制。本研究结果表明，ILF-RE 通过抑制肝氧化应激和脂生成，对慢性 CCl4 诱导的肝损伤发挥保护作用，提示 ILF-RE 是一种治疗肝毒性和相关功能障碍的潜在天然产物。
