Rajendra Sangaraju1,2, Nasiruddin Nalban1,2, Sateesh Alavala1, Vinoth Rajendran1, Mahesh Kumar Jerald3, Ramakrishna Sistla4,5. 1. Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India. 2. Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201 002, India. 3. Animal House Facility, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, 500 007, India. 4. Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India. sistla@iict.res.in. 5. Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201 002, India. sistla@iict.res.in.
Abstract
OBJECTIVE AND DESIGN: Inflammatory bowel disease (IBD) is known to cause chronic inflammation in the digestive tract by the immune malfunction. Herein, we demonstrate the protective effect of galangin (GAL), a phytochemical, on LPS-induced inflammation in cultured mouse macrophages (RAW 264.7) and the treatment of DSS-induced ulcerative colitis in Balb/c mice. However, the anti-inflammatory effect of GAL in DSS-exposed experimental colitis has not been investigated. MATERIALS AND METHODS: We determined the levels of proinflammatory cytokines by ELISA, biochemical analysis using standard protocols and protein expression level of NF-κB signaling pathway and activation of Nrf2 gene pathway were analyzed by western blot analysis in colitis-induced mice. RESULTS: Our in vitro studies showed that LPS-stimulated RAW 264.7 cells treated with GAL reduced the levels of nitrites, IL-6, and TNF-α in a concentration-dependent manner. The results demonstrated that oral administration of GAL at 20 mg/kg (lower dose) and 40 mg/kg (higher dose) significantly reduced the severity of colitis and mitigated the clinical signs of both macroscopic and microscopic of the disease. The levels of proinflammatory cytokines (TNF-α and IL-6) in colonic tissue and serum were reduced significantly and in GAL + DSS-treated group relative to DSS alone treated group. Increased levels of anti-inflammatory cytokine (IL-10) was detected in colon tissues in GAL + DSS-treated groups relative to DSS alone treated group. We also observed decreased levels of myeloperoxidase (MPO), nitrites and TBARS with increased SOD in colonic tissue of GAL + DSS group. Besides, GAL + DSS-treated animals significantly suppressed protein expressions of p-NF-κB and p-Ikk-βα, COX-2, iNOS, Nrf2 and increased HO-1 levels in colon tissues by inhibiting inflammation and oxidative stress. CONCLUSION: Our study highlights the protective effect of galangin as an anti-inflammatory agent against the severe form of colitis in pre-clinical models suggesting its potency for the treatment of IBD in humans.
OBJECTIVE AND DESIGN:Inflammatory bowel disease (IBD) is known to cause chronic inflammation in the digestive tract by the immune malfunction. Herein, we demonstrate the protective effect of galangin (GAL), a phytochemical, on LPS-induced inflammation in cultured mouse macrophages (RAW 264.7) and the treatment of DSS-induced ulcerative colitis in Balb/c mice. However, the anti-inflammatory effect of GAL in DSS-exposed experimental colitis has not been investigated. MATERIALS AND METHODS: We determined the levels of proinflammatory cytokines by ELISA, biochemical analysis using standard protocols and protein expression level of NF-κB signaling pathway and activation of Nrf2 gene pathway were analyzed by western blot analysis in colitis-induced mice. RESULTS: Our in vitro studies showed that LPS-stimulated RAW 264.7 cells treated with GAL reduced the levels of nitrites, IL-6, and TNF-α in a concentration-dependent manner. The results demonstrated that oral administration of GAL at 20 mg/kg (lower dose) and 40 mg/kg (higher dose) significantly reduced the severity of colitis and mitigated the clinical signs of both macroscopic and microscopic of the disease. The levels of proinflammatory cytokines (TNF-α and IL-6) in colonic tissue and serum were reduced significantly and in GAL + DSS-treated group relative to DSS alone treated group. Increased levels of anti-inflammatory cytokine (IL-10) was detected in colon tissues in GAL + DSS-treated groups relative to DSS alone treated group. We also observed decreased levels of myeloperoxidase (MPO), nitrites and TBARS with increased SOD in colonic tissue of GAL + DSS group. Besides, GAL + DSS-treated animals significantly suppressed protein expressions of p-NF-κB and p-Ikk-βα, COX-2, iNOS, Nrf2 and increased HO-1 levels in colon tissues by inhibiting inflammation and oxidative stress. CONCLUSION: Our study highlights the protective effect of galangin as an anti-inflammatory agent against the severe form of colitis in pre-clinical models suggesting its potency for the treatment of IBD in humans.