Biochemistry and Cell Culture Laboratory, Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, 695019, India.
Biofactors. 2014 Nov-Dec;40(6):646-57. doi: 10.1002/biof.1193. Epub 2014 Dec 20.
The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPARγ). Naturally occurring PPARγ modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPARγ activity. In the present work, we studied chebulagic acid (CHA) isolated from fruits of Terminalia chebula with respect to its effect on adipogenesis, glucose transport, and endocrine function of adipocyte. The mRNA expression profile of PPARγ target gene CCAAT/enhancer-binding protein alpha (C/EBP-α) was analyzed by qRT-PCR. The putative binding mode and the potential ligand-target interactions of CHA, with PPARγ was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARγ signaling and adipogenesis dose dependently but in a moderate way, less than rosiglitazone. GLUT4 expression and adiponectin secretion was increased by CHA treatment. The mRNA expression of PPARγ target gene C/EBP-α was increased in CHA -treated adipocytes. The comparison of results of various parameters of adipogenesis, insulin sensitivity, endocrine function and molecular docking experiments of roziglitazone and chebulagic acid indicate that the latter behaves like partial PPARγ agonist which could be exploited for phytoceutical development against T2DM.
噻唑烷二酮（TZDs）类药物对 2 型糖尿病（T2DM）的治疗非常有效。但由于合成 TZDs 的不良反应，其使用受到严格限制。TZDs 的治疗作用是通过调节过氧化物酶体增殖物激活受体γ（PPARγ）介导的。天然存在的 PPARγ 调节剂更受欢迎，因为它们缺乏 TZDs 引起的严重不良反应。这促使人们利用传统医学中使用的药用植物，挖掘其潜在的 PPARγ 活性。在本工作中，我们研究了从诃子果实中分离得到的诃子酸（CHA）对脂肪生成、葡萄糖转运和脂肪细胞内分泌功能的影响。通过 qRT-PCR 分析了 PPARγ 靶基因 CCAAT/增强子结合蛋白α（C/EBP-α）的 mRNA 表达谱。使用对接软件（Autodock 和 iGEMDOCKv2）分析了 CHA 与 PPARγ 的可能结合模式和潜在的配体-靶相互作用。结果表明，CHA 可增强 PPARγ 信号和脂肪生成，呈剂量依赖性，但程度适中，低于罗格列酮。CHA 处理可增加 GLUT4 表达和脂联素分泌。在 CHA 处理的脂肪细胞中，PPARγ 靶基因 C/EBP-α 的 mRNA 表达增加。对罗格列酮和诃子酸在脂肪生成、胰岛素敏感性、内分泌功能等各种参数的结果比较和分子对接实验表明，后者表现为部分 PPARγ 激动剂，可用于开发植物药治疗 2 型糖尿病。
