Piper longum Linn. Extract inhibits TNF-alpha-induced expression of cell adhesion molecules by inhibiting NF-kappaB activation and microsomal lipid peroxidation.
Recruitment of specific leukocyte subpopulations at the site of inflammation requires a series of cell adhesion molecule (CAM)-mediated interactions. The major CAMs, viz., intercellular adhesion molecule-1 (ICAM-1), VCAM-1 and E-selectin are expressed on endothelium in response to various cytokines or bacterial LPS. Here, we have evaluated the effect of Piper longum chloroform extract (PlCE) on TNF-alpha-induced expression of ICAM-1 on endothelial cells and on NADPH-catalyzed rat liver microsomal lipid peroxidation with a view to identify modulators for the expression of CAMs. We demonstrate that PlCE inhibits adhesion of neutrophils to endothelial monolayer. This inhibition is due to the ability of PlCE to significantly block the TNF-alpha-induced expression of CAMs, i.e. ICAM-1, VCAM-1 at 17.5 microg/ml concentration and E-selectin at 15 microg/ml concentration on human umbilical vein endothelial cells. The inhibition of ICAM-1, VCAM-1 and E-selectin by PlCE is mediated through inhibition of NF-kappaB in endothelial cells. To demonstrate the antioxidant activity of PlCE, we showed that PlCE inhibited the NADPH-catalyzed rat liver microsomal lipid peroxidation significantly. These results suggest a possible mechanism of anti-inflammatory as well as antioxidant activity of PlCE.
Singh
Naresh
N
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, University of Delhi Campus (North), Mall Road, Delhi 110 007, India.
Kumar
Sarvesh
S
Singh
Prabhjot
P
Raj
Hanumantharao G
HG
Prasad
Ashok K
AK
Parmar
Virinder S
VS
Ghosh
Balaram
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D031701:Piper; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009249:NADP