An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down-regulation of nitric oxide.
The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for the relief of pain; however, the underlying molecular mechanisms of this effect have not been elucidated. The anti-inflammatory and immunomodulatory effects of an ethanolic extract of the leaves of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant-induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose-dependent decrease in extracellular production of nitric oxide in murine peritoneal macrophages was measured by the Griess assay and corroborated by flow cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2 diacetate. This decreased generation of reactive nitrogen species was mediated by PB progressively down-regulating transcription of inducible nitric oxide synthase in macrophages, and concomitantly causing a dose-dependent decrease in the expression of interleukin-12 p40, indicating the ability of PB to down-regulate T-helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and anti-arthrotic activity of PB is attributable to its ability to down-regulate the generation of reactive nitrogen species, thus meriting further pharmacological investigation.
Ganguly
Sudipto
S
Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya Jagadish Chandra Bose Road, Kolkata-700 020, West Bengal.
Mula
Soumyaditya
S
Chattopadhyay
Subrata
S
Chatterjee
Mitali
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D053762:Interleukin-12 Subunit p40 / Q000187:drug effects / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008519:Medicine, Traditional; D051379:Mice; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D008517:Phytotherapy; D031721:Piper betle / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; D053762:Interleukin-12 Subunit p40; D010936:Plant Extracts; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II