Anti-inflammatory activity of rhein isolated from the flowers of Cassia fistula L. and possible underlying mechanisms

Abstract EN

Objective: Anti-inflammatory activity of rhein in animal models with potential mechanism of actions.

Methods: Rhein was isolated from Cassia fistula L.

flowers collected in Chennai, Tamil Nadu, India.

Its antiinflammatory activity was then investigated in Wistar rats and mice using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, cotton pellet-induced granuloma and acetic acid-induced vascular permeability models.

Results: Administration of rhein (10, 20, 40 mg/kg) significantly (p < 0.05) inhibited carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice in dose-dependent manners.

Continual administration of rhein to rats using implanted cotton pellets significantly (p < 0.05) reduced granuloma formation (20 mg/kg: 17.24%; 40 mg/kg: 36.12%) compared to control group animals.

Administration of rhein increased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and decreased the levels of nitrite, interleukin-6 (IL-6), interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) compared to control animals.

Western blotting results revealed that rhein diminished carrageenan-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and increased heme oxygenase (HO)-1, nuclear factor erythroid 2–related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR)-c and heat shock protein (HSP)-72 expression after 6 h in the paw oedema model.

Conclusion: The anti-inflammatory mechanisms of rhein might be related to decrease in the levels of MDA, iNOS and COX-2 and the stimulation of HO-1, PPAR-c and Nrf2 expression via increases in the activities of CAT, SOD and GSH-px through the suppression of nitrite, TNF-a, IL-6 and IL-1b.