Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Cimiracemate A confers protection on arthritic neonatal rats via regulation of iNOS/NF-κB/TLR-4 pathway

Jun Zou¹, Kun Peng², Tao Xiong³, Zhi G Xiong¹, Niya Hu¹

¹Department of Pediatric Orthopedic, Jiangxi Provincial Children's Hospital, Nanchang 330000; ²Department of Orthopedic, The Second Affiliated Hospital of Nanchang University, Nanchang 330006; ³Department of Orthopedic, Jiangxi Provincial Cancer Hospital, Nanchang 330029; ⁴Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang 330008, China.

For correspondence:- Niya Hu Email: AlanzThomasqt@yahoo.com Tel:+8679188692748

Accepted: 20 April 2019 Published: 31 May 2019

Citation: Zou J, Peng K, Xiong T, Xiong ZG, Hu N. Cimiracemate A confers protection on arthritic neonatal rats via regulation of iNOS/NF-κB/TLR-4 pathway. Trop J Pharm Res 2019; 18(5):949-954 doi: 10.4314/tjpr.v18i5.6

© 2019 The authors.
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Abstract

Purpose: To investigate the protective effect of cimiracemate A on Freund’s adjuvant-induced rheumatoid arthritis (RA) in neonatal rats, and the underlying mechanism.

Methods: Rheumatoid arthritis was induced in rat pups using Complete Freund’s adjuvant (100 µg/100 µL/body weight) which was intra-dermally injected at the tail region. After 21 days of establishment of RA, the rats were randomly assigned to four groups of ten rats each: control group, RA group, 5 mg/kg cimiracemate A group, and 10 mg/kg cimiracemate A group. Cimiracemate A was orally administered for 45 days. The effect of cimiracemate A on oxidative stress biomarkers, superoxide dismutase (SOD), malondialdehyde (MDA) and reduced glutathione (GSH) were determined using standard methods. Plasma levels of the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE-2) and matrix metalloproteinase-3 (MMP-3) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the levels of protein expressions of iNOS, NF-κB and TLR-4.

Results: The level of MDA significantly increased and the level of GSH significantly decreased in RA group relative to control group (p < 0.05) following treatment with cimiracemate A. SOD activity was significantly reduced in RA group, when compared with control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently reversed the altered levels of MDA and GSH and SOD activity, when compared with RA group (p < 0.05). Plasma levels of IL-1β, TNF-α, PGE-2 and MMP-3 were significantly higher in RA group than in control group, but were significantly and dose-dependently reduced after treatment with cimiracemate A (p < 0.05). There were significant increases in the levels of expression of iNOS, NF-κB and TLR-4 proteins in the chondrocytes of RA group, relative to control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently down-regulated the expressions of these proteins, when compared with RA group (p < 0.05).

Conclusion: The results of this study indicate that cimiracemate A confers some degree of protection on arthritic neonatal rats via a mechanism that involves regulation of iNOS/NF-κB/TLR-4 pathway.

Keywords: Rheumatoid arthritis, Cimiracemate A, Chondrocytes, Oxidative stress, Inflammatory cytokines