Abstract

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement–drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement–drug interaction.

摘要

可以以膳食补充剂的形式使用植物来源的抗氧化分子。然而，大多数这些产品的膳食补充剂-药物相互作用模式尚未明确定义。本研究的目的是确定黄连素、白藜芦醇和格列本脲对糖尿病大鼠外源性代谢酶活性的影响。给予链脲佐菌素以产生实验性糖尿病。白藜芦醇 (5 mg/kg) (R)、格列本脲 (5 mg/kg) (G) 和小檗碱 (10 mg/kg) (B) 通过腹膜内给药途径在 DMSO 中单独或联合给药至糖尿病大鼠。DMSO 也给予非糖尿病对照组 (C) 和糖尿病对照组 (D)。在治疗期结束时（12天）在麻醉下取大鼠肝脏。乙氧基试卤灵 O-脱乙基酶 (EROD), 在微粒体和胞质溶胶中测量戊氧基试卤灵 O-去戊基化酶 (PROD)、苯胺 4-羟化酶 (A4H)、红霉素 N-去甲基化酶 (ERND)、谷胱甘肽 S-转移酶 (GST)、过氧化氢酶 (CAT) 和谷胱甘肽还原酶 (GR) 活性. 此外，还在肝组织中进行了组织形态学研究。D+R的EROD活性显着高于C和D+R+B。D+R的PROD活性显着高于C、D、D+R+G、D+R+B和D+R+B+G。D+B的PROD活性显着高于C和D+R+ B. D+R的ERND活性显着高于D+R+G和D+R+B。D+R的GST活性显着高于D+R+G。D+B 的 CAT 活性显着低于 C。显然白藜芦醇、黄连素、格列本脲改变了一些重要的外源性代谢酶活性。白藜芦醇和小檗碱有可能引起膳食补充剂-药物相互作用。