HEALING THROUGH CYTOKINE REGULATION IN DNBS INDUCED INFLAMMATORY BOWEL DISEASE IN RATS BY HOLARRHENA ANTIDYSENTERICA

Abstract

The objective of the study was to ascertain antioxidant, anti-inflammatory and cytokine gene regulation activity of Holarrhena antidysenterica (HA) in dinitrobenzene sulfonic acid (DNBS) induced inflammatory bowel disease (IBD) in rats. Sprague Dawley rats were divided into 6 groups, Group I (normal), Group II (50% ethanol intracolonically on 11th day), Group III (Model). Group IV to VI were given standard drug 5-amino salicylic acid (5-ASA) (100mg/kg) and hydromethanolic extract of Holarrhena antidysenterica (MEHA) 450 mg/kg and MEHA 600 mg/kg respectively for 18 days once p.o. Colitis was induced with DNBS (180mg/kg in 50% ethanol) intracolonically in animals of Group III-VI on 11th day. Body weight, food & water intake and stool consistency of each group was noted. On 18th day, blood was collected for cortisol estimation. Colon length and weight was measured. Cytokine gene expression studies of colon in group I, II, III, IV and VI was done using Real Time RT-PCR. Colon histopathology, Disease Activity Index (DAI) and Colon Mucosal Disease index (CMDI) parameters were studied. Nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) were estimated in colon homogenate. DNBS model control showed significant reduction in body weight, water and food intake, SOD, colon length and significant increase in stool consistency, colon weight, MDA, MPO, NO, CMDI, DAI, cortisol, IL-4, IL-6, IL-12 and IFN-gamma cytokines gene expression. Pretreatment with 5-ASA (100mg/kg) and MEHA (450 and 600 mg/kg) significantly reversed the above. MEHA reduced severity of IBD induced by DNBS through its anti-inflammatory, antioxidant and gene modulatory activity.