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

Paulrayer Antonisamy; Paul Agastian; Chang-Won Kang; Nam Soo Kim; Jong-Hoon Kim

doi:10.1016/j.sjbs.2017.04.011

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

Saudi J Biol Sci. 2019 Jan;26(1):96-104. doi: 10.1016/j.sjbs.2017.04.011. Epub 2017 Apr 28.

Authors

Paulrayer Antonisamy¹, Paul Agastian², Chang-Won Kang¹, Nam Soo Kim¹, Jong-Hoon Kim¹

Affiliations

¹ College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 5459679 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
² Department of Plant Biology and Biotechnology, Loyola College, Chennai 600 034, Tamil Nadu, India.

Abstract

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 anti-inflammatory 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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)-γ 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-γ and Nrf2 expression via increases in the activities of CAT, SOD and GSH-px through the suppression of nitrite, TNF-α, IL-6 and IL-1β.

Keywords: ANOVA, one-way analysis of variance; AUC, area under the curve; Anti-inflammatory; C.fistula, Cassiafistula L.; CAT, catalase; CMC, carboxymethylcellulose; COX-2, cyclooxygenase-2; Cassia fistula; Ear oedema; GSH-px, glutathione peroxidase; HSP-72, heat shock protein; IL-1β, interleukin-1β; IL-6, interleukin-6; MDA, malondialdehyde; MPO, myeloperoxidase; Nrf2, nuclear factor erythroid 2–related factor 2; PPAR-γ, peroxisome proliferator-activated receptor gamma; Paw oedema; Rats; Rhein; SOD, superoxide dismutase; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor; WHO, World Health Organization; iNOS, inducible nitric oxide synthase.