Park Eun-Jeon, Zhao Yu-Zhe, Kim Young Ho, Lee Jung Joon, Sohn Dong Hwan
Department of Pharmacy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Planta Med. 2004 Apr;70(4):321-7. doi: 10.1055/s-2004-818943.
The aim of this study was to investigate the protective effect of acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum, on liver injury induced by either tert-butyl hydroperoxide (tBH) or carbon tetrachloride in vitro and in vivo. In vitro, the cellular leakage of lactate dehydrogenase (LDH) following treatment with 1.5 mM tBH for 1 h, was significantly inhibited by co-treatment with acanthoic acid (25 and 5 microg/mL) and the ED (50) of acanthoic acid was 2.58 microg/mL (8.5 microM). The cellular leakage of LDH following one hour of treatment with 2.5 mM CCl (4) was significantly inhibited by co-treatment with acanthoic acid (25 microg/mL) and the ED (50) of acanthoic acid was 4.25 microg/mL (14.1 microM). Co-treatment with acanthoic acid significantly inhibited the generation of intracellular reactive oxygen species (ROS) and intracellular glutathione (GSH) depletion induced by tBH or CCl (4). Acanthoic acid pretreatment (100 mg/kg per day for four consecutive days, p. o.) significantly reduced levels of aspartate transaminase and alanine transaminase in acute liver injury models induced by either tBH or carbon tetrachloride. Treatment with acanthoic acid (100 mg/kg, p. o.) at 6, 24, and 48 hours after carbon tetrachloride subcutaneous injection significantly reduced the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in CCl (4)-injured liver were improved upon treatment with acanthoic acid. In vivo treatment with acanthoic acid was not able to modify CYP2E1 activity and protein expression in liver microsomes at the dose used, showing that the hepatoprotective effect of acanthoic acid was not mediated through inhibition of CCl (4) bioactivation. From the results above, acanthoic acid had a protective effect against tBH- or CCl (4)-induced hepatotoxicity in vitro and in vivo.
本研究旨在探讨从朝鲜五加根皮中分离得到的二萜类化合物刺五加酸对叔丁基过氧化氢（tBH）或四氯化碳在体外和体内诱导的肝损伤的保护作用。在体外，用1.5 mM tBH处理1小时后，乳酸脱氢酶（LDH）的细胞渗漏被刺五加酸（25和5微克/毫升）共同处理显著抑制，刺五加酸的半数有效剂量（ED50）为2.58微克/毫升（8.5微摩尔）。用2.5 mM四氯化碳处理1小时后，LDH的细胞渗漏被刺五加酸（25微克/毫升）共同处理显著抑制，刺五加酸的ED50为4.25微克/毫升（14.1微摩尔）。刺五加酸共同处理显著抑制了tBH或四氯化碳诱导的细胞内活性氧（ROS）生成和细胞内谷胱甘肽（GSH）消耗。刺五加酸预处理（连续四天每天100毫克/千克，口服）显著降低了tBH或四氯化碳诱导的急性肝损伤模型中天冬氨酸转氨酶和丙氨酸转氨酶的水平。在四氯化碳皮下注射后6、24和48小时用刺五加酸（100毫克/千克，口服）处理显著降低了血清中天冬氨酸转氨酶和丙氨酸转氨酶的水平。组织学观察显示，用刺五加酸处理后，四氯化碳损伤肝脏中的脂肪酸变化、肝细胞坏死和炎性细胞浸润得到改善。在体内，以所用剂量用刺五加酸处理不能改变肝微粒体中CYP2E1的活性和蛋白表达，表明刺五加酸的肝保护作用不是通过抑制四氯化碳生物活化介导的。从上述结果来看，刺五加酸在体外和体内对tBH或四氯化碳诱导的肝毒性具有保护作用。
