Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Biomed Pharmacother. 2018 Jun;102:728-738. doi: 10.1016/j.biopha.2018.03.097. Epub 2018 Apr 5.
Quercus dilatata Lindl. ex Royle was evaluated for in vitro polyphenol content and antioxidant potential as well as in vivo protective role against bisphenol A (BPA) induced hepatotoxicity. The distilled water-acetone (QDDAE) and methanol-ethyl acetate (QDMEtE) extracts were standardized and administered in high (300 mg/kg body weight (BW) and low (150 mg/kg BW) doses to Sprague Dawley rats, injected with BPA (25 mg/kg BW). Silymarin (50 mg/kg BW) was used as positive control. Subsequently, blood and liver homogenates were collected after four weeks of treatment, and the defensive effects of both extracts against oxidative damage and genotoxicity were assessed via hematological and biochemical investigations, determination of endogenous expression of enzymes as well as levels of free radicals and comet assay. Between the two extracts, maximum phenolics (213 ± 0.15 μg gallic acid equivalent/mg dry extract (DE) and flavonoids (55.6 ± 0.16 μg quercetin equivalent/mg DE) content, DPPH scavenging activity (IC: 8.1 ± 0.5 μg/ml), antioxidant capacity (53.7 ± 0.98 μg ascorbic acid equivalent (AAE)/mg DE) and reducing potential (228.4 ± 2.4 μg AAE/mg DE) were observed in QDMEtE. In in vivo analysis, a dose dependent hepatoprotective activity was exhibited by both the extracts. QDDAE demonstrated maximum reduction in levels of alanine transaminase (49.77 ± 3.83 U/l), thiobarbituric acid reactant substances (33.46 ± 0.70 nM/min/mg protein), hydrogen peroxide (18.08 ± 0.01 ng/mg tissue) and nitrite (55.64 ± 1.79 μM/ml), along with decline in erythrocyte sedimentation rate (4.13 ± 0.072 mm/h), histopathological injuries and DNA damage in BPA intoxicated rats as compared with QDMEtE. Likewise, QDDAE also significantly restored activity levels of endogenous antioxidants, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (POD) and GSH with values of 6.46 ± 0.15 U/mg protein, 6.87 ± 0.1 U/min, 11.94 ± 0.17 U/min and 16.86 ± 1.56 nM/min/mg protein, respectively. Comparative results were obtained for QDMEtE. In conclusion, the present study endorses the significant hepatoprotective potential of standardized extracts of Q. dilatata with known polyphenolics content and validates the traditional use of this plant in natural medicine to manage disorders like hepatotoxicity.
已评估扩张栎（Quercus dilatata Lindl. ex Royle）的水提丙酮（QDDAE）和甲醇-乙酸乙酯（QDMEtE）提取物的体外多酚含量和抗氧化潜力，以及对双酚 A（BPA）诱导的肝毒性的体内保护作用。提取物经标准化后，以高剂量（300mg/kg 体重（BW）和低剂量（150mg/kg BW）施用于 Sprague Dawley 大鼠，同时注射 BPA（25mg/kg BW）。水飞蓟素（50mg/kg BW）用作阳性对照。四周治疗后收集血液和肝匀浆，通过血液学和生物化学研究、内源性酶表达的测定以及自由基和彗星试验水平来评估两种提取物对氧化损伤和遗传毒性的防御作用。在这两种提取物中，QDMEtE 中观察到最大的酚类（213±0.15µg 没食子酸当量/mg 干提取物（DE）和类黄酮（55.6±0.16µg 槲皮素当量/mg DE）含量、DPPH 清除活性（IC：8.1±0.5µg/ml）、抗氧化能力（53.7±0.98µg 抗坏血酸当量（AAE）/mg DE）和还原能力（228.4±2.4µg AAE/mg DE）。在体内分析中，两种提取物均表现出剂量依赖性的肝保护活性。QDDAE 表现出丙氨酸转氨酶（49.77±3.83U/l）、硫代巴比妥酸反应物（33.46±0.70nM/min/mg 蛋白）、过氧化氢（18.08±0.01ng/mg 组织）和亚硝酸盐（55.64±1.79µM/ml）水平的最大降低，同时红细胞沉降率（4.13±0.072mm/h）、组织病理学损伤和 DNA 损伤也有所降低，与 QDMEtE 相比，BPA 中毒大鼠的 DNA 损伤有所降低。同样，QDDAE 还显著恢复了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（POD）和 GSH 的内源性抗氧化剂活性水平，分别为 6.46±0.15U/mg 蛋白、6.87±0.1U/min、11.94±0.17U/min 和 16.86±1.56nM/min/mg 蛋白。QDMEtE 也得到了类似的结果。综上所述，本研究支持已标准化的扩张栎提取物具有显著的保肝潜力，且多酚含量已知，验证了该植物在天然药物中用于治疗肝毒性等疾病的传统用途。
