Quercetin exhibits hepatoprotective activity in rats
Quercetin exhibits hepatoprotective activity in rats
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DOI：
10.1042/bst025s619
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发表时间：
1997-11-01
影响因子：
3.9
通讯作者：
Shah, BH
中科院分区：
文献类型：
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作者：
Gilani, AH;Janbaz, KH;Shah, BH
槲皮素是一种黄酮类化合物，存在于东莨菪碱（AS）和其他一些植物中[1]。它具有抗炎[2]、抗氧化和自由基清除[3]、抗肿瘤[4]和钙拮抗剂[5]活性。AS传统上用于纠正肝损伤。在我们以前的研究中，我们证明了这种民间医疗用途具有科学合理的基础，因为这种植物的粗提取物在肝毒性动物模型中显示出保肝活性[6]。本研究使用瑞士雄性小鼠（20-25 g）和雄性白化病Wistar大鼠（200-250 g），饲养在阿加汗大学的动物之家，保持在23-25 ℃。对小鼠进行初步实验以评估槲皮素对致死剂量的扑热息痛（1 g/kg）的保护作用。将动物分成2组，每组10只动物。一组口服槲皮素（10 mg/kg），1小时后口服对乙酰氨基酚（1 g/kg）。第二组作为对照，接受相同的治疗，不同之处在于施用生理盐水（0.9%NaCl）代替测试药物。在对乙酰氨基酚给药后24小时内观察死亡率。通过口服混悬于1%甲基纤维素中的对乙酰氨基酚（640 mg/Kg）造成肝损伤。将大鼠分为3组，每组10只动物。第1组作为溶剂对照，口服生理盐水和溶剂。第2组以12小时间隔接受4次生理盐水（10 ml/kg）给药，并在最后一次给药后1小时经口给予对乙酰氨基酚。第3组的处理与第2组相似，不同之处在于施用槲皮素（10 mg/kg）而不是盐水。最后一次给药后24小时，用氯胺酮（100 mg/Kg，im）麻醉动物，并使用无菌一次性注射器通过心脏穿刺采集血液（3 mL）。通过离心（3000 rpm，15 min）分离血清，并在同一天使用Merck诊断试剂盒通过荧光定量法估计血清转氨酶（GOT和GPT）。对乙酰氨基酚在小鼠中以1 g/kg的剂量经口给药产生100%的死亡率，而用槲皮素（10 mg/kg）预处理动物将死亡率降低至30%。图1显示了槲皮素对扑热息痛诱导的肝毒性的影响。对乙酰氨基酚（640 mg/Kg;口服）对大鼠产生肝损伤，表现为血清GOT和GPT分别显著升高（P< 0.05）至813 f158、475 f124 IU/L（平均值fSEM; n= 10），而相应对照值为89 f13和41 f10。预处理的大鼠槲皮素（10毫克/公斤;口服）显着降低（P< 0.05），分别血清GOT和GPT水平为105 f 11和46 f 09。对乙酰氨基酚诱导的肝损伤是保肝药物戒断的常用模型[71]。血清转氨酶水平的升高归因于肝脏结构完整性受损，因为这些酶位于细胞质中，并在细胞损伤后释放到循环中[8]。槲皮素似乎可以保持肝细胞膜的结构完整性。这从向小鼠提供的针对致死剂量的
Quercetin is a flavonoid present in Artemisia scopunu (AS) and some other plants [l]. It possesses anti-inflammatory [2] antioxidant and free radical scavenging [3], anti-tumor [4] and calcium antagonist [5] activities. AS has been used traditionally to correct liver damage. In our previous studies, we demonstrated that this folkmedical use had scientifically justified basis as the crude extract of this plant showed hepatoprotective activity in an animal model of hepatotoxicity [6]. The aim of this investigation was to see whether quercetin exhibits hepatoprotective activity, which may explain the folkloric use of this plant in hepatitis.Swiss male mice (20-25 g) and male albino Wistar rats (200-250 g) housed at the Animal House of The Aga Khan University, maintained at 23-25 C were used for this study. Preliminary experiments were performed on mice to estimate the protective effect of quercetin against lethal dose of paracetamol (1 glkg). Animals were divided into 2 groups of 10 animals each. One group was treated orally with quercetin (10 mg/kg) followed after one hour by oral administration of paracetamol (1 g/kg). The second group served as a control and received same treatment except that normal saline (0.9% NaCI) was administered instead of test drug. The mortality was observed for 24 hrs post-administration of paracetamol. Hepatic injury was produced by oral administration of paracetamol (640 mg/Kg) suspended in 1% methylcellulose. Rats were divided into 3 groups each containing 10 animals. Group 1 served as vehicle control and received normal saline and vehicle orally. Group 2 received 4 doses of normal saline (10 ml/kg) at 12 hrs interval and paracetamol was administered orally one hr post-treatment of the last dose. Group 3 was treated similar to the group 2 except that quercetin (10 mg/kg) was administered instead of saline. Animals were anaesthetized with ketamine (100 mg/Kg, im) 24 hrs after the last treatment and blood (3 mL) was collected by cardiac puncture using sterile disposable syringes. Serum was separated by centrifugation (3000 rpm, for 15 min) and serum aminotransaminases (GOT and GPT) were estimated on the same day spectrophotometrically using Merck diagnostic kits. Oral administartion of paracetamol produced 100% mortality at the dose of 1 g/kg in mice while pretreatment of animals with quercetin (10 mg/kg) reduced the death rate to 30%. Figure 1 shows the effect of quercetin on paracetamolinduced hepatotoxicity. Paracetamol (640 mg/Kg; orally) produced liver damage in rats as manifested by significant rise (P< 0.05) in serum GOT and GPT to 813 f 158, 475 f 124 IU/L (mean f SEM; n= 10) respectively compared to respective control values of 89 f 13 and 41 f 10. Pretreatment of rats with quercetin (10 mg/kg; orally) lowered significantly (P< 0.05) the respective serum GOT and GPT levels to 105 f 11 and 46 f 09. Liver injury induced by paracetamol is commonly used models for theweening of hepatoprotective drugs [7l. The rise in serum levels of transaminases has been attributed to the damaged structural integrity of the liver because these are cytoplasmic in location and are released into circulation after cellular damage [8]. Quercetin seems to preserve the structural integrity of the hepato-cellular membrane. This was evident from the protection provided to mice against lethal dose of