Inhibition of MAP kinases by crude extract and pure compound isolated from Commiphora mukul leads to down regulation of TNF-alpha, IL-1beta and IL-2.
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.
Manjula
N
N
Centre for Biotechnology, Anna University, Chennai 600 025, India.
Gayathri
B
B
Vinaykumar
K S
KS
Shankernarayanan
N P
NP
Vishwakarma
R A
RA
Balakrishnan
A
A
D000085:Acetates; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D029744:Commiphora / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000085:Acetates; D007202:Indicators and Reagents; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D010936:Plant Extracts; D012333:RNA, Messenger; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C007650:ethyl acetate; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases; C022616:thiazolyl blue