Saravanan Munisankar, Pandikumar Perumal, Saravanan Subramaniam, Toppo Erenius, Pazhanivel Natesan, Ignacimuthu Savarimuthu
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Nungambakkam, Chennai 600034, India.
Department of Veterinary Pathology, Madras Veterinary College, Vepery, Chennai 600007, India.
Eur J Pharmacol. 2014 Oct 5;740:714-21. doi: 10.1016/j.ejphar.2014.06.004. Epub 2014 Jun 18.
Aegle marmelos Correa., (Rutaceae) is a medium sized tree distributed in South East Asia and used traditionally for the management of obestiy and diabetes. In this study the lipolytic and antiadipogenic effects of (3,3-dimethylallyl) halfordinol (Hfn) isolated from leaves of A. marmelos have been investigated. Intracellular lipid accumulation was measured by oil red O staining and glycerol secretion. The expression of genes related to adipocyte differentiation was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Hfn decreased intracellular triglyceride accumulation and increased glycerol release in a dose dependent manner (5-20 μg/ml) in differentiated 3T3-L1 adipocytes. In high fat diet fed C57/BL 6J mice, treatment with Hfn for four weeks reduced plasma glucose, insulin and triglyceride levels and showed a significant reduction in total adipose tissue mass by 37.85% and visceral adipose tissue mass by 62.99% at 50mg/kg b.w. concentration. RT-PCR analyses indicated that Hfn decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α (CEBPα) and increased the expression of sterol regulatory enzyme binding protein (SREBP-1c), peroxisome proliferator-activated receptor α (PPARα), Adiponectin and Glucose transporter protein 4 (GLUT4) compared to the high fat diet group. These results suggested that Hfn decreased adipocyte differentiation and stimulated lipolysis of adipocytes. This study justifies the folklore medicinal uses and claims about the therapeutic values of this plant for the management of insulin resistance and obesity.
印度枳椇（芸香科）是一种中型树木，分布于东南亚地区，传统上用于治疗肥胖症和糖尿病。在本研究中，对从印度枳椇叶片中分离得到的（3,3-二甲基烯丙基）半多灵醇（Hfn）的脂解和抗脂肪生成作用进行了研究。通过油红O染色和甘油分泌来测定细胞内脂质积累情况。采用逆转录聚合酶链反应（RT-PCR）分析与脂肪细胞分化相关基因的表达。在分化的3T3-L1脂肪细胞中，Hfn以剂量依赖性方式（5-20μg/ml）降低细胞内甘油三酯积累并增加甘油释放。在高脂饮食喂养的C57/BL 6J小鼠中，以50mg/kg体重的浓度给予Hfn治疗四周后，可降低血浆葡萄糖、胰岛素和甘油三酯水平，总脂肪组织质量显著降低37.85%，内脏脂肪组织质量显著降低62.99%。RT-PCR分析表明，与高脂饮食组相比，Hfn降低了过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT增强子结合蛋白α（CEBPα）的表达，并增加了固醇调节酶结合蛋白（SREBP-1c）、过氧化物酶体增殖物激活受体α（PPARα）、脂联素和葡萄糖转运蛋白4（GLUT4）的表达。这些结果表明，Hfn可减少脂肪细胞分化并刺激脂肪细胞的脂解作用。本研究证实了该植物在治疗胰岛素抵抗和肥胖症方面的民间药用价值及治疗功效。
