Amelioration of adjuvant induced arthritis in Sprague Dawley rats through modulation of inflammatory mediators by Ribes alpestre Decne

J Ethnopharmacol. 2019 May 10:235:460-471. doi: 10.1016/j.jep.2019.02.025. Epub 2019 Feb 13.

Abstract

Ethnopharmacological relevance: Ribes alpestre Decne has been commonly used in the treatment of joint complaints.

Aim of study: The present study was undertaken to evaluate the antiarthritic potential of ethanolic extract and fractions of Ribes alpestre and to explore its probable mechanism of action.

Material and methods: Complete Freunds adjuvant induced arthritis in Sprague Dawley rats was used to assess antiarthritic activity of aqueous ethanol extract, butanol and aqueous fractions at 200 mg/kg oral dose for 28 days. Paw volume and diameter, arthritic index, body weight, hematological and biochemical parameters, radiographic and histological analysis of ankle joints were carried out. An array of pro-inflammatory mediators (IL-1β, IL-6, NF-Kβ, TNF-α, COX-2, IL-4, IL-10 and PGE2) were estimated by RT-PCR and enzyme linked immunosorbent assay. Antioxidant capacity was assessed using DPPH and reducing power assays. Qualitative phytochemical screening, total phenolic and flavonoid content and HPLC analysis of aqueous fraction of Ribes alpestre were also carried out.

Results: Significant (p < 0.001) reduction in paw volume and thickness and arthritic score by aqueous ethanolic extract and its fractions has been found. Aqueous ethanolic extract and fractions in particular aqueous fraction considerably prevented decrease in body weight, alterations in hematological parameters. Radiographic and histological examination revealed no significant architectural changes in joints of treated rats. Significant (p < 0.05-0.001) down regulation of pro-inflammatory genes IL-1β, TNF-α, IL-6, COX-2, PGE2 and NF-Kβ alongwith noteworthy increase in levels of IL-4 and IL-10 was recorded among treated animals. Aqueous ethanol extract and its fractions demonstrated notable and concentration dependent (50-6400 μg/ml) antioxidant potential. Qualitative phytochemical analysis of active fraction (aqueous) displayed presence of flavonoids, alkaloids, tannins and glycosides. Besides total phenolic and flavonoid contents has been found to be 179.3 mg GAE/ml and 389.40 μg QE/ml in aqueous fraction of Ribes alpestre respectively. HPLC profile demonstrated presence of quercitin, chlorogenic acid, vanillic acid and cinamic acid in aqueous fraction.

Conclusion: Present communication suggests Ribes alpestre a potent antiarthritic therapy by ameliorating adjuvant arthritis in rats by downregulating proinflammatory mediators with up regulation of anti-inflammatory cytokines.

Keywords: Arthritic score; CFA; ELISA; Phytochemical analysis; Pro-inflammatory mediators; RT-PCR; Ribes alpestre.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / isolation & purification
  • Antirheumatic Agents / pharmacology
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Chromatography, High Pressure Liquid
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Freund's Adjuvant
  • Inflammation Mediators / metabolism
  • Male
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Ribes / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Antirheumatic Agents
  • Cytokines
  • Inflammation Mediators
  • Plant Extracts
  • Freund's Adjuvant