title: Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract.
abstract: Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action.
authors.affiliation: Department of Physiology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata, 700009, India.
authors.forename: Madhura
authors.initials: M
authors.lastname: Bose
authors.forename: Mousumi
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Sourav
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Debarati
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Suvra
authors.initials: S
authors.lastname: Mandal
authors.forename: Roshnara
authors.initials: R
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001578:Benzopyrans / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D033641:Millettia / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C052068:karanjin
keywords: Karanjin; NF-κB; Pongamia pinnata; adjuvant induced arthritis; arthritis score