Phytochemical mediated modulation of COX-3 and NFκB for the management and treatment of arthritis

Author:

Biswas Dipak,Somkuwar Bharat Gopalrao,Borah Jagat Chandra,Varadwaj Pritish Kumar,Gupta Saurabh,Khan Zeeshan Ahmad,Mondal Gopinath,Chattoraj Asamanja,Deb Lokesh

Abstract

AbstractIn this study, we investigated whether zerumbone (ZBN), ellagic acid (ELA) and quercetin (QCT), the plant-derived components, can modulate the role of COX-3 or cytokines liable in arthritic disorder. Initially, the effect of ZBN, ELA, and QCT on inflammatory process was investigated using in-vitro models. In-silico docking and molecular dynamics study of these molecules with respective targets also corroborate with in-vitro studies. Further, the in-vivo anti-arthritic potential of these molecules in Complete Freund’s adjuvant (CFA)-induced arthritic rats was confirmed. CFA increases in TNF-α and IL-1β levels in the arthritic control animals were significantly (***p < 0.001) attenuated in the ZBN- and ELA-treated animals. CFA-induced attenuation in IL-10 levels recovered under treatment. Moreover, ELA attenuated CFA-induced upregulation of COX-3 and ZBN downregulated CFA-triggered NFκB expression in arthritic animals. The bonding patterns of zerumbone in the catalytic sites of targets provide a useful hint in designing and developing suitable derivatives that can be used as a potential drug. To our best knowledge, the first time we are reporting the role of COX-3 in the treatment of arthritic disorders which could provide a novel therapeutic approach for the treatment of inflammatory disorders.

Funder

Indian Council of Medical Research

Department of Biotechnology, Ministry of Science and Technology, India

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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