Zhu Jing-Jie, Huang Jun-Shang, Wang Ting, Ji Jun, Hou Ai-Jun, Wang He-Yao
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
Endocrine. 2017 Apr;56(1):73-81. doi: 10.1007/s12020-016-1203-3. Epub 2016 Dec 21.
Adipose tissue is not only a lipid storage site, but also a well-known endocrine organ. Dysfunction of adipose tissue is associated with irregular lipid metabolism, ectopic lipid accumulation and insulin resistance. It is proposed that modulating on adipose tissue is a reasonable way to ameliorate glucose and lipid metabolism. (±)-sanggenol F (SGF, purity >98.5%) was synthesized as a racemic mixture of natural (+)-sanggenol F. In this study, SGF was found to promote adipocyte differentiation, enhance insulin sensitivity, and upregulate beneficial adipokines expression in 3T3-L1 cells. Furthermore, in vivo study showed that treatment with SGF for 4 weeks improved glucose metabolism, by decreasing fasting blood glucose and enhancing insulin sensitivity. It also improved lipid metabolism, with reduced serum lipid level and ameliorated hepatic steatosis in db/db mice. During the process of target finding, we found that SGF had multiple activities of protein tyrosine phosphatase 1B inhibition, peroxisome proliferator-activated receptor γ and peroxisome proliferator-activated receptor α agonism. These results showed the potential of SGF as a candidate for the therapy of type 2 diabetes.
脂肪组织不仅是脂质储存部位，也是一个广为人知的内分泌器官。脂肪组织功能障碍与脂质代谢异常、异位脂质堆积和胰岛素抵抗相关。有人提出调节脂肪组织是改善糖脂代谢的合理途径。（±）-桑根醇F（SGF，纯度>98.5%）作为天然（+）-桑根醇F的外消旋混合物被合成。在本研究中，发现SGF可促进3T3-L1细胞的脂肪细胞分化，增强胰岛素敏感性，并上调有益脂肪因子的表达。此外，体内研究表明，用SGF治疗4周可改善糖代谢，降低空腹血糖并增强胰岛素敏感性。它还改善了脂质代谢，降低了db/db小鼠的血脂水平并改善了肝脂肪变性。在靶点寻找过程中，我们发现SGF具有抑制蛋白酪氨酸磷酸酶1B、激活过氧化物酶体增殖物激活受体γ和过氧化物酶体增殖物激活受体α的多种活性。这些结果表明SGF作为2型糖尿病治疗候选药物的潜力。
