Ji Jun, Zhu Jingjie, Hu Xiao, Wang Ting, Zhang Xiaodong, Hou Ai-Jun, Wang Heyao
Department of Pharmacognosy, School of Pharmacy, Fudan University, 826 Zhang Heng Road, Pudong, Shanghai 201203, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
Biochem Biophys Res Commun. 2015 May 8;460(3):578-82. doi: 10.1016/j.bbrc.2015.03.072. Epub 2015 Mar 20.
Adipose tissue plays a key role in the development of obesity and diabetes. Natural products are one of the main sources for discovering new lead compounds. In the present study, (2S)-7,4'-dihydroxy-8-prenylflavan (DHPF), a natural prenylated flavan isolated from Morus yunnanensis, was found to significantly promote adipogenesis and increase glucose uptake in 3T3-L1 cells. Real-time PCR results showed that DHPF increased the expression of glucose and lipid metabolism-related genes (C/EBPα, PPARγ, aP2, GLUT4 and adiponectin) and decreased the expression of inflammatory cytokine TNF-α. Western blotting further revealed that DHPF activated p38 MAPK at the initial stage of 3T3-L1 preadipocyte differentiation. DHPF-induced activation of p38, adipogenesis and glucose uptake were effectively blocked by SB203580, a specific p38 inhibitor. These results indicate that DHPF could stimulate adipogenesis and increase glucose uptake through the p38 MAPK pathway, and DHPF may be useful for the prevention and treatment of obesity-associated disorders such as type 2 diabetes (T2D).
脂肪组织在肥胖症和糖尿病的发展过程中起着关键作用。天然产物是发现新先导化合物的主要来源之一。在本研究中，从滇桑中分离得到的一种天然异戊烯基黄酮（2S）-7,4'-二羟基-8-异戊烯基黄酮（DHPF），被发现能显著促进3T3-L1细胞的脂肪生成并增加葡萄糖摄取。实时定量PCR结果显示，DHPF增加了葡萄糖和脂质代谢相关基因（C/EBPα、PPARγ、aP2、GLUT4和脂联素）的表达，并降低了炎性细胞因子TNF-α的表达。蛋白质印迹法进一步显示，DHPF在3T3-L1前脂肪细胞分化的初始阶段激活了p38丝裂原活化蛋白激酶（p38 MAPK）。DHPF诱导的p38激活、脂肪生成和葡萄糖摄取被特异性p38抑制剂SB203580有效阻断。这些结果表明，DHPF可通过p38 MAPK途径刺激脂肪生成并增加葡萄糖摄取，并且DHPF可能对预防和治疗肥胖相关疾病如2型糖尿病（T2D）有用。
