Modulation of Th1/Th2 cytokines and inflammatory mediators by hydroxychavicol in adjuvant induced arthritic tissues.
The present study was undertaken to investigate the anti-arthritic activity of hydroxychavicol (HC) a major phenolic compound isolated from the aqueous extract leaves of plant Piper betle (Piperaceae). The compound showed significant lowering of pro-inflammatory (Th1) cytokine levels in arthritic paw tissue homogenate supernatant viz. IL-2, IFN-gamma, and TNF-alpha with maximum inhibition at higher dose levels of 2 and 4 mg/kg p.o. and enhanced the production of anti-inflammatory (Th2) cytokines IL-4 and IL-5 estimated by cytometric bead array immunoassay. Cytometric bead array uses the sensitivity of amplified fluorescence detection by flowcytometer to measure soluble analytes in a particle based immune assay. This assay can accurately quantitate five cytokines in a 50-microl sample volume. The T-helper (Th1) deviated cells produce detectable level of tumor necrosis factor (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma), while the Th2 deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin-5 (IL-5). HC at graded doses also significantly decreased the expression of IL-1beta, PGE(2), LTB(4), and nitric oxide levels showing significant inhibition of these parameters. Elevated levels of CD4(+) T cell specific interferon-gamma (IFN-gamma) in splenocytes of arthritic animals was also inhibited in treated animals. The oral LD(0) in both mice and rats was more than 1000 mg/kg.
Cell Biology Laboratory, Department of Pharmacology, Indian Institute of Integrative Medicine, Jammu Tawi 180001, India. anjali290284@yahoo.co.in
Anjali
A
Pandey
Sarang
S
Bani
Prabhu
P
Dutt
Krishna Avtar
KA
Suri
D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D005260:Female; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods; D018836:Inflammation Mediators / Q000276:immunology*; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D031721:Piper betle / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018501:Antirheumatic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; C051268:2-hydroxychavicol; D005054:Eugenol