Chemistry Department, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah, 30002, Saudi Arabia.
Molecular Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
Biochemistry (Mosc). 2021 Feb;86(2):179-189. doi: 10.1134/S0006297921020061.
Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1β mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.
虎杖苷（PD）具有广泛的药理活性；然而，其对糖尿病肝损伤的作用研究甚少。本研究旨在探讨载虎杖苷壳聚糖纳米粒（PD-CSNPs）或 PD 对糖尿病相关肝损伤的可能保护作用。采用烟酰胺/链脲佐菌素处理诱导大鼠糖尿病。然后将糖尿病大鼠分为六组：正常对照组大鼠、糖尿病对照组大鼠和每日口服 PD、PD-CSNPs、等量未载药壳聚糖纳米粒或二甲双胍治疗 4 周的大鼠。与糖尿病对照组大鼠相比，PD 和 PD-CSNPs 治疗显著降低了血糖含量、肝脂质过氧化、血清转氨酶和糖代谢酶（琥珀酸脱氢酶和丙酮酸激酶）活性；相反，肝糖原含量、谷胱甘肽浓度、抗氧化酶（超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和葡萄糖-6-磷酸脱氢酶）活性显著升高。此外，肿瘤坏死因子α和白细胞介素 1βmRNA 的表达显著下调，而葡萄糖转运蛋白 2和葡糖激酶 mRNA 的表达则显著上调。综上，PD-CSNPs 和 PD 通过调节葡萄糖转运蛋白 2 的表达、影响糖代谢酶的活性、抑制氧化应激和炎症，改善糖尿病肝损伤，其中 PD-CSNPs 比 PD 更有效，可能是由于其生物利用度更高和释放更持久。
