Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Molecules. 2023 Jan 4;28(2):483. doi: 10.3390/molecules28020483.
The stem of has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of , was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5' AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms.
的茎在传统的印度医学体系中被用于控制血糖，但人们并不知道导致观察到的抗糖尿病作用的潜在机制和化学成分。在本研究中，从 的茎中分离得到的二萜类化合物替诺福昔，因其对骨骼肌细胞葡萄糖利用的影响而被研究，随后在我们的糖尿病 db/db 小鼠模型中测定其抗高血糖功效。我们发现，替诺福昔通过增加 GLUT4 向肌管质膜的易位，在延长 16 小时的暴露后增加葡萄糖摄取。此外，替诺福昔处理显著增加了蛋白激酶 B/AKT（Ser-473）和 5' AMP 激活的蛋白激酶（AMPK，Thr-172）的磷酸化。在存在wortmannin 和 compound C 的情况下，这些作用被消除。替诺福昔给药可改善 db/db 小鼠的葡萄糖耐量和外周胰岛素敏感性，与骨骼肌组织中磷酸肌醇 3-激酶（PI3Ks）和 AMPK 信号标志物的基因表达和磷酸化增加有关。研究结果表明，替诺福昔通过增强骨骼肌葡萄糖利用的速率发挥其抗糖尿病作用，这是由 PI3K 和 AMPK 依赖性信号机制介导的。
