Lim Sung Ho, Yu Jae Sik, Lee Ho Seon, Choi Chang-Ik, Kim Ki Hyun
BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Pharmaceutics. 2021 Apr 9;13(4):526. doi: 10.3390/pharmaceutics13040526.
(Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from and their underlying mechanisms of action. Consequently, in this study, the fruits of were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3--β-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.
桑科植物，即白桑，在传统东方医学中被用于治疗发热、保护肝脏免受损伤、改善视力以及降低血糖水平。关于从白桑中鉴定出的抗糖尿病化合物及其潜在作用机制的研究较少。因此，在本研究中，利用3T3-L1脂肪细胞对白桑果实中的潜在抗糖尿病天然产物进行了研究。对白桑果实乙醇提取物进行植物化学分析，随后通过高效液相色谱（HPLC）进行纯化，分离出两种主要化合物：芦丁和槲皮素-3-β-D-葡萄糖苷（Q3G）。长期使用现有的2型糖尿病（T2D）治疗药物往往伴随着不良副作用，这使得人们对开发更有效、更安全的抗糖尿病药物的兴趣日益增加。在3T3-L1脂肪细胞中检测分离出的化合物芦丁和Q3G的抗糖尿病或抗肥胖特性或两者，结果表明它们均通过Akt介导的胰岛素信号通路或激活3T3-L1脂肪细胞中的AMP激活蛋白激酶（AMPK）来改善葡萄糖摄取。这些化合物还对脂肪细胞中的脂质积累产生了积极影响，表明葡萄糖摄取是通过激活Akt和AMPK信号通路实现的，而不会诱导脂肪生成。综上所述，我们的研究结果表明，白桑果实中的芦丁和Q3G可能产生较少的副作用，如体重增加，并且这些活性化合物可能是治疗T2D的潜在候选药物。
