Abstract
In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (-)-O-methylcubebin (MC), (-)-hinokinin, and (-)-cubebin, were isolated from the ethyl acetate extract of the leaves of V. trifolia, using various chromatography. Among the three isolated compounds, MC showed the strongest effects to increase intracellular lipid accumulation in 3T3-L1 cells. From the results of the elucidation of the MC’s effects on the adipogenesis of 3T3-L1 cells, the downsizing of adipocytes and the promotion of the expression of adipogenesis-related proteins, as well as adiponectin, were observed. On the other hand, since the activity of MC was inhibited by antagonists of PPARγ and improved by inhibitors of the classical mitogen-activated protein kinase (MAPK) pathway and p38MAPK pathway, MC was considered to be an agonist of PPARγ, and furthermore promoted adipogenesis via the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK phosphorylation. Although MC showed similar effects to those of rosiglitazone (RO) used as a positive control, RO promoted the migration of GLUT4 from the cytoplasm to the cell membrane, whereas MC did not show such an effect. From the abovementioned results, it was considered that MC could be a lead compound for the development of antidiabetic drugs that does not show weight gain, which is a side effect of RO.
Highlights
Type 2 diabetes (T2D) affects more than 300 million people worldwide [1] and is one of the leading causes of death
We previously reported that vitexylactone isolated from V. trifolia was a ligand for peroxisome proliferator-activated receptor γ (PPARγ) and promoted adipogenesis [21]
Three known lignans were isolated from V. trifolia in this study
Summary
Type 2 diabetes (T2D) affects more than 300 million people worldwide [1] and is one of the leading causes of death. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor that plays a crucial role in the regulation of glucose homeostasis and lipid metabolism, and it is considered to be one of the important targets for the treatment of metabolic disorders of T2D. The European Diabetes Association no longer recommends rosiglitazone, one of typical TZDs, for the treatment of T2D [5]. To avoid the side effects of TZDs, various strategies have been considered to develop compounds that act as ligands of PPARγ with fewer side effects. Several groups have shown that post-translational modification of PPARγ induced by different ligands affects the transcriptional effects on specific target genes, but an alternative medicine for TZD has not been developed yet [10,11,12]
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