Iridoid glycosides from the flowers of Gentiana macrophylla Pall. ameliorate collagen-induced arthritis in rats

The flowers of Gentiana macrophylla have been usually applied to cure the joint inflammation and rheumatoid arthritis in Traditional Chinese Medicine.This work aimed to investigate the anti-rheumatoid arthritic effect and possible mechanism of iridoid glycosides from G. macrophylla (GMI) using an animal model of collagen-induced rheumatoid arthritis (CIA) in rats.All rats were randomly divided into five groups: normal control, CIA, dexamethasone, 15mg/kg and 30mg/kg GMI.CIA was induced (day 0) in male Sprague-Dawley rats by intradermal injection of complete Bovine CII at the base of the tail. Dexamethasone was chosen as the positive drug. The administration of different drugs started from day 1 and continued for 28 days. Paw swelling, arthritis score and histopathological changes were examined to assess the severity of arthritis. In addition, the serum levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in joint synovial tissues were detected.GMI reduced paw edema, arthritis scores and the index of spleen and thymus from day 7 to 21 after CIA compared with those in the CIA group. Our data also demonstrated that GMI inhibited pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, regulated the expression of iNOS and COX-2 compared with those in the CIA group. We also obtained four major components from GMI, identified as loganic acid, swertamarin, gentiopicroside and sweroside, and the contents of them were also calculated respectively.Taken together, our results shed light on the therapeutic efficacy of GMI in rats rheumatoid arthritis model by reducing the levels of IL-1β, IL-6 and TNF-α in serum as well as down-regulating the levels of iNOS and COX-2. Therefore, GMI may be an effective therapy for the treatment of rheumatoid arthritis.