Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin 300301, China; Tianjin Institute of Pharmaceutical Research Drug Safety Assessment Co., Ltd., Tianjin 300301, China.
Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin 300301, China.
Chin J Nat Med. 2018 Aug;16(8):590-598. doi: 10.1016/S1875-5364(18)30096-7.
Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
梓醇是地黄中的一种主要生物活性成分，已被用于治疗糖尿病。本研究旨在阐明梓醇对 db/db 小鼠的抗糖尿病作用及其作用机制。将 db/db 小鼠根据血糖水平随机分为六组（每组 10 只）：db/db 对照组、二甲双胍（阳性对照）和四个梓醇剂量组（25、50、100 和 200mg·kg），10 只 db/m 小鼠作为正常对照组。所有组均进行 8 周的口服给药。分析空腹血糖（FBG）、随机血糖（RBG）、葡萄糖耐量、胰岛素耐量、糖化血清蛋白（GSP）和肝脏组织中的基因表达水平。结果显示，梓醇处理可显著降低 db/db 小鼠的摄水量和摄食量，呈剂量依赖性。梓醇处理还可显著降低空腹血糖（FBG）和随机血糖（RBG），呈剂量依赖性。梓醇的降 RBG 作用优于二甲双胍。此外，梓醇可通过提高胰岛素敏感性显著改善葡萄糖耐量和胰岛素耐量。梓醇处理可显著降低 GSP 水平。正常对照组、db/db 对照组和梓醇处理组（200 和 100mg·kg）的肝脏组织基因表达比较表明，287 个基因的表达明显增加，这些基因主要涉及脂质代谢、应激反应、能量代谢和细胞过程，520 个基因的表达明显降低，这些基因主要涉及细胞生长、死亡、免疫系统和应激反应。4 个差异表达的基因与葡萄糖代谢或胰岛素信号通路有关，包括 Irs1（胰岛素受体底物 1）、Idh2（异柠檬酸脱氢酶 2（NADP+），线粒体）、G6pd2（葡萄糖-6-磷酸脱氢酶 2）和 SOCS3（细胞因子信号转导抑制因子 3）。总之，梓醇通过调节多种基因表达，对 db/db 小鼠发挥显著的降血糖作用和显著的治疗作用。
