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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01341

Invivo and invitro approach to anti- arthritic and anti- inflammatory effect of Crocetin by alteration of Nuclear Factor-E2-related Factor 2/hem Oxygenase (HO)-1 and NF-κB expression

 Jian Wang1,  Rajat Kakkar2* and Yi Li1
  • 1Department of Joint Surgery, Shandong Provincial Hospital, China
  • 2Chandrasheker College of Pharmacy, India

The aim of the current experimental investigation to scrutinize the anti-inflammatory effect of Crocetin using the lipopolysaccharide (LPS) induced mouse macrophages (RAW 264.7) in vitro and complete Freund's adjuvant-induced arthritis model and explore invivo and explore the possible mechanism of action. RAW 264.7 macrophages were used for estimation of the effect of Crocetin on the COX-2, NO production, anti-inflammatory and inflammatory mediators (IL-10). Single intraperitoneal injection of CFA was used to induce arthritis. The rats were divided into different group and received the oral administration of Crocetin at dose-dependently and indomethacin till 28 days. The paw edema and body weight estimated at regular interval. The biochemical parameters, haematological and pro-inflammatory cytokines such as TNF-R1, IL-6, and IL-1β, VEGF; HO-1/Nrf-2 expression were estimated at end of the experimental study. At end of the experimental study, the histopathological study was also performed. Crocetin inhibited the COX-2 catalyzed PGE2 and inducible nitric oxide synthase catalyzed NO production on RAW 264.7. The paw edema and body weight was significantly (P<0.001) modulated by the Crocetin in a concentration-dependent manner. Crocetin treatment showed the modulation of biochemical and hematological parameters. Crocetin showed the alteration of TNF-α, IL-6, and IL-1β in a dose-dependent manner. The protective effect of crocetin was substantiated with reduced the expression of IL-6, IL-1β, VEGF, and TNF-R1, respectively. Crocetin also increased the HO-1/Nrf-2 and decreased the NF-κB mRNA, protein expression. On the basis of the result, we can conclude that reduction of HO-1/Nrf-2 expression, as well as inflammatory mediators, may be involved in the protective effect of Crocetin.

Keywords: Crocetin, Enzymatic hydrolysis, Arthritis, RAW 264.7 macrophage, Inflammation

Received: 11 Aug 2018; Accepted: 31 Oct 2018.

Edited by:

Mohamed M. Abdel-Daim, Suez Canal University, Egypt

Reviewed by:

Marta C. Monteiro, Universidade Federal do Pará, Brazil
Eman Mehanna, Faculty of Pharmacy, Suez Canal University, Egypt  

Copyright: © 2018 Wang, Kakkar and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Rajat Kakkar, Chandrasheker College of Pharmacy, Allahabad, India, rajatkakkar1980@gmail.com