Abstract
Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.
Highlights
Drugs based on these products have been used in the prevention and treatment of many inflammatory disorders
PT-Mangiferin at 40 μM dose was more effective in reducing the level of Reactive Oxygen Species (ROS) than standard ROS inhibitor, N-acetyl cysteine (NAC)
NF-κB translocation is responsible for expression of inflammatory proteins like COX-2, inducible nitric oxide synthase (iNOS), TNF-α
Summary
Drugs based on these products have been used in the prevention and treatment of many inflammatory disorders. They interfere with inflammatory mechanisms preventing prolonged inflammatory processes that are problematic for human health. Several natural products were known to have anti-inflammatory effects but very few products like Aloe Vera, Curcumin, Ginseng and Resveratrol have demonstrated their anti-inflammatory effects via inactivation of NLRP3 inflammosome[6,7,8,9,10,11,12,13]. Few studies have demonstrated the anti-inflammatory property of Mangiferin, the molecular mechanism of its effect on inflammaosomes has not been completely elucidated[18,19,20]. In this study we isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and determined its anti-inflammatory mechanism in most reliable mouse air pouch model of inflammation
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