Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur 302 055, India; Department of Zoology, Dyal Singh College, University of Delhi, Lodhi Road, New Delhi 110 003, India.
Department of Zoology, Dyal Singh College, University of Delhi, Lodhi Road, New Delhi 110 003, India.
J Ethnopharmacol. 2015 Feb 23;161:186-93. doi: 10.1016/j.jep.2014.12.025. Epub 2014 Dec 24.
α-Amyrin (a pentacyclic triterpene widely distributed in nature and isolated from a variety of plant sources and pharmacologically shown a wide spectrum of activity including anti-inflammatory, anti-ulcer, anti-hyperlipidemic, anti-tumor, and hepatoprotective actions) explored as hepatomodulator from the ethanol extract of the stem bark of Alstonia scholaris Linn. against CCl4-induced hepatic oxidative stress through antioxidant status in wistar albino rats.
Experimental rats, hepato-oxidatively stressed by CCl4 (0.2 ml/kg b wt/twice a week, intra-peritoneally), were concurrently received α-amyrin (20mg/kg body weight/day, orally) for 30 consecutive days. Hepatomodulatory potential was assessed by using the serum- markers like γ-glutamyl transpeptidase (GGT), aspartate and alanine transaminases (AST, ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), and total bilirubin, total protein, glutathione reduced (GSH), ceruloplasmin, β-carotene, vitamin C and vitamin E in serum concomitantly with the hepatic-antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and 5´-nucleotidase, acid ribonuclease, glucose-6-phosphatase, succinic dehydrogenase and cytochrome-P-450 in liver tissue whereas lipid peroxidation (LPO) was estimated in both serum and liver contents.
The assessment of all biochemical parameters registered a significant (P<0.001) hepatic oxidative stress in CCl4 treated rats, which was considerably recovered near to almost normal level in rats co-administered with α-amyrin at the dose level of 20mg/kg body weight/day for 30 consecutive days. The histoarchitectural examination of liver sections from treated groups further corroborated the hepatomodulatory potential of α-amyrin and compared with standard drug-silymarin.
These findings indicate that the modulatory potential of α-amyrin against hepatic oxidative stress possibly involve mechanism related to its ability to block the P-450 mediated CCl4 bioactivation through selective inhibitors of ROS (reactive oxygen species) as antioxidants brought about significant inhibition of the formation of LPO suggesting possible involvement of O2(●-), HO2, HO2(●-), H2O2 and •OH. Therefore this study suggests that the use of α-amyrin as a hepatomodulatory potent to feasibility for a promising liver curative drug.
关键词: 阿马林;肝氧化应激;抗氧化剂;丙二醛;脂质过氧化
摘要: 目的:研究从夹竹桃科植物阿马林对 CCl4 诱导的肝氧化应激的乙醇提取物中分离得到的 α- 角鲨烯作为肝调节剂的潜力。方法:采用分光光度法测定血清 γ- 谷氨酰转肽酶(GGT)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)、酸性磷酸酶(ACP)、山梨醇脱氢酶(SDH)、谷氨酸脱氢酶(GDH)和总胆红素、总蛋白、还原型谷胱甘肽(GSH)、铜蓝蛋白、β- 胡萝卜素、维生素 C 和维生素 E 等血清标志物,同时测定肝超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)、谷胱甘肽 S- 转移酶(GST)和 5´- 核苷酸酶、酸性核糖核酸酶、葡萄糖-6- 磷酸酶、琥珀酸脱氢酶和细胞色素 P-450 等肝抗氧化剂。结果:CCl4 处理大鼠的所有生化参数均显著升高(P<0.001),而同时给予 α- 角鲨烯(20mg/kg 体重/天)治疗 30 天可使大鼠的肝氧化应激得到显著改善(P<0.001)。与标准药物水飞蓟素相比,α- 角鲨烯对 CCl4 处理大鼠肝组织的形态结构也有明显的改善作用。结论:这些结果表明,α- 角鲨烯对肝氧化应激的调节作用可能与其抑制 P-450 介导的 CCl4 生物活化的能力有关,通过选择性抑制 ROS(活性氧)作为抗氧化剂,显著抑制 LPO 的形成,提示 O2(●-)、HO2、HO2(●-)、H2O2 和 •OH 可能参与其中。因此,本研究表明,α- 角鲨烯作为肝调节剂具有潜在的应用价值,可能成为一种有前途的肝脏治疗药物。