Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-kappaB pathway

Debjani Sarkar; Piu Saha; Sunita Gamre; Surajit Bhattacharjee; Chellaram Hariharan; Sudipto Ganguly; Rupashree Sen; Goutam Mandal; Subrata Chattopadhyay; Subrata Majumdar; Mitali Chatterjee

doi:10.1016/j.intimp.2008.05.003

Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-kappaB pathway

Int Immunopharmacol. 2008 Sep;8(9):1264-71. doi: 10.1016/j.intimp.2008.05.003. Epub 2008 Jun 6.

Authors

Debjani Sarkar¹, Piu Saha, Sunita Gamre, Surajit Bhattacharjee, Chellaram Hariharan, Sudipto Ganguly, Rupashree Sen, Goutam Mandal, Subrata Chattopadhyay, Subrata Majumdar, Mitali Chatterjee

Affiliation

¹ Department of Zoology, Dinabandhu Mahavidyalaya, Bongaon, West Bengal, Pin-743235, India.

PMID: 18602073
DOI: 10.1016/j.intimp.2008.05.003

Abstract

The crude ethanol extract of Piper betle leaf is reported to possess anti-inflammatory activity which has been suggested to be mediated by allylpyrocatechol (APC). In the present study, we have demonstrated the anti-inflammatory effects of APC (10 mg/kg, p.o.) in an animal model of inflammation. To investigate the mechanism(s) of this anti-inflammatory activity, we examined its effects on the lipopolysaccaride (LPS)-induced production of NO and PGE(2) in a murine macrophage cell line, RAW 264.7. APC inhibited production of NO and PGE(2) in a dose dependent manner as also decreased mRNA expression of iNOS, COX-2, IL-12p40 and TNF-alpha. Since nuclear factor-kappaB (NF-kappaB) appears to play a central role in transcriptional regulation of these proteins, we investigated the effects of APC on this transcription factor. APC inhibited LPS induced nuclear factor-kappaB (NF-kappaB) activation, by preventing degradation of the inhibitor kappaB (IkappaB). Taken together, our data indicates that APC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2 and IL-12 p40 through down regulation of the NF-kappaB pathway, indicating that APC may have therapeutic potential in inflammation associated disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal*
Blotting, Western
Catechols / pharmacology*
Cell Line
Cell Survival / drug effects
Chromatography, High Pressure Liquid
Cyclooxygenase 2 / biosynthesis*
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 Inhibitors / pharmacology*
Dinoprostone / analysis
Dinoprostone / biosynthesis
Edema / chemically induced
Edema / pathology
Inflammation Mediators / metabolism
Lipopolysaccharides / pharmacology*
Macrophages / drug effects
Macrophages / metabolism*
Macrophages / pathology
Male
Mice
NF-kappa B / biosynthesis*
NF-kappa B / genetics
Nitric Oxide / analysis
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / antagonists & inhibitors*
Nitric Oxide Synthase Type II / biosynthesis
Nitric Oxide Synthase Type II / genetics
Phosphorylation / drug effects
Plant Extracts / chemistry
Plant Leaves / chemistry
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction

Substances

Anti-Inflammatory Agents, Non-Steroidal
Catechols
Cyclooxygenase 2 Inhibitors
Inflammation Mediators
Lipopolysaccharides
NF-kappa B
Plant Extracts
allylpyrocatechol
Nitric Oxide
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Dinoprostone