Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway

• Published in: Biochimica et biophysica acta Vol. 1850; no. 4; pp. 769 - 783
• Main Authors: Sinha, Krishnendu, Sadhukhan, Pritam, Saha, Sukanya, Pal, Pabitra Bikash, Sil, Parames C.
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.2015
• Subjects: absorption; adhesion; adverse effects; Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; antioxidants; Antioxidants - pharmacology; apoptosis; Apoptosis - drug effects; biosynthesis; Cyclooxygenase 2 - analysis; cytokines; enzyme-linked immunosorbent assay; enzymes; Flavonoids - pharmacology; Gastric Emptying - drug effects; gastric mucosa; Gastric Mucosa - drug effects; Gastritis - prevention & control; I-kappa B Proteins - metabolism; indomethacin; Indomethacin - toxicity; inflammation; Male; medicinal properties; Mitochondria - drug effects; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; nonsteroidal anti-inflammatory agents; oxidative stress; pathogenesis; pharmacokinetics; prostaglandins; Rats; Rats, Sprague-Dawley; reverse transcriptase polymerase chain reaction; reversed-phase high performance liquid chromatography; Signal Transduction - drug effects; transcription factor NF-kappa B; Anti-inflammatory compound; Inflammation; Morin; Antioxidant; Gastropathy; NSAID
• ISSN: 0304-4165; 0006-3002
• DOI: 10.1016/j.bbagen.2015.01.008

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent.