ABSTRACT
The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.
Subject(s)
Aegle , Glucose/metabolism , Phytotherapy , Plant Extracts/pharmacology , Syzygium , Animals , Biological Transport/drug effects , Glucose Transporter Type 4/metabolism , In Vitro Techniques , Muscle Fibers, Skeletal/cytology , PPAR gamma/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/chemistry , Rats , Up-Regulation/drug effectsABSTRACT
The anti-inflammatory effect of the medicinal plant, Commiphora mukul gum was studied in peripheral blood mononuclear cells (PBMC). Bioassay-guided fractionation using conventional solvent extraction procedures, subsequent column fractionation, followed by monitoring specific activity in PBMC led to the isolation of a lead compound. Both crude ethyl acetate extract and the lead compound, thus isolated, showed inhibitory effect on proliferative response of PBMC in mitogenic lymphocyte proliferation and MLR assays. Further studies on inflammatory mediators such as IFN-gamma, IL-12, TNF-alpha, IL-1beta and NO showed down regulation, whereas no inhibition was observed in the case of anti-inflammatory cytokine IL-10. Immunoblot analysis revealed the inhibitory effect of crude ethyl acetate extract on phosphorylation of all the three mitogen activated protein kinases (MAPK) such as ERK, JNK and p38 MAPK. In contrast treatment with pure compound showed no inhibitory effect on ERK. c-fos and c-jun mRNA levels were also reduced in PMA stimulated cells on treatment with crude extract and pure compound. This reduction in c-fos and c-jun levels, when taken together with inhibition of MAPK activation, provides a possible mechanism by which both crude ethyl acetate extract and purified compound isolated from C. mukul exert its action.
Subject(s)
Commiphora/chemistry , Interleukin-1/biosynthesis , Interleukin-2/biosynthesis , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis , Acetates , Animals , Blotting, Western , Cell Proliferation/drug effects , Down-Regulation/drug effects , Genes, fos/drug effects , Genes, jun/drug effects , Humans , Indicators and Reagents , Interleukin-1/antagonists & inhibitors , Interleukin-2/antagonists & inhibitors , Lymphocyte Culture Test, Mixed , Macrophages/drug effects , Macrophages/metabolism , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Phytohemagglutinins/pharmacology , Plant Extracts/pharmacology , RNA, Messenger/biosynthesis , Solvents , Tetrazolium Salts , Thiazoles , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
The purpose of the present study is to analyse the influence of Pterocarpus marsupium methanolic extract and isolated Pterocarpus marsupium isoflavone on a battery of cellular targets Glut-4, PPAR gamma and PI3 kinase. Pterocarpus marsupium is an anti-diabetic plant indigenous to South India. Sequential extraction performed with different solvents were analysed for glucose uptake activity at each step. Fraction-9 showing maximum glucose activity on glucose uptake was purified by column chromatography and the structure was elucidated as 7-O-alpha-L-rhamnopyranosyl oxy-4'-methoxy-5-hydroxy isoflavone using NMR and mass spectroscopy. The significant glucose uptake showed by Pterocarpus marsupium crude and pure was comparable with insulin and rosiglitazone. Elevation of Glut-4 and PPARgamma gene expression in parallel with glucose uptake supported the in vitro glucose uptake activity of Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone. The inhibitory effect of cycloheximide on Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone-mediated glucose uptake suggested that new protein synthesis is required for elevated Glut-4 protein expression. PI3 kinase plays an important role in glucose transport and activated by Pterocarpus marsupium methanolic extract but not the isolated pure isoflavone. Therefore, we postulate that the isoflavone from Pterocarpus marsupium may activate glucose transport by a PI3 kinase independent pathway, which require further analysis.