Berberis aristata Ameliorates Adjuvant-Induced Arthritis by Inhibition of NF-κB and Activating Nuclear Factor-E2-related Factor 2/hem Oxygenase (HO)-1 Signaling Pathway

ABSTRACT

The present study was carried out to investigate the anti-arthritic activity of Berberis aristata hydroalcoholic extract (BAHE) in formaldehyde-induced arthritis and adjuvant-induced arthritis (AIA) model. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. In formaldehyde-induced arthritis and AIA, treatment of BAHE at doses 50, 100 and 200 mg/kg orally significantly decreased joint inflammation as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological examination. BAHE treatment demonstrated dose-dependent improvement in the redox status of synovium (decrease in GSH, MDA, and NO levels and increase in SOD and CAT activities). The beneficial effect of BAHE was substantiated with decreased expression of inflammatory markers such as IL-1β, IL-6, TNF-R1, and VEGF by immunohistochemistry analysis in AIA model. BAHE increased HO-1/Nrf-2 and suppressed NF-κB mRNA and protein expression in adjuvant immunized joint. Additionally, BAHE abrogated degrading enzymes, as there was decreased protein expression of MMP-3 and -9 in AIA. In conclusion, we demonstrated the anti-arthritic activity of Berberis aristata hydroalcoholic extract via the mechanism of inhibition of NF-κB and activation of Nrf-2/HO-1.

KEYWORDS:

• Adjuvant-induced arthritis
• angiogenesis
• Berberis aristata
• pro-inflammatory cytokines

Acknowledgments

We are thankful to Natural Remedies Pvt. Ltd., Bangalore, India for providing a generous gift of Berberis aristata extract and its HPLC standardization part. The authors are grateful to Brijesh Kumar, Head, Sophisticated Analytical Instrument Facility (SAIF), CSIR – Central Drug Research Institute, Lucknow, India, for carrying out mass spectral studies. Sample reference no. in SAIF facility is SAIF/2013/8854.

Declaration of interest

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the article. The authors declare that even though the same normal, control and standard drug group were used in testing various test compounds, they do not have a bearing on each other and do not affect the efficacy data of test drugs reported in other papers.

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