title: Iridoid glycosides from the flowers of Gentiana macrophylla Pall. ameliorate collagen-induced arthritis in rats.
abstract: BACKGROUND
  The flowers of Gentiana macrophylla have been usually applied to cure the joint inflammation and rheumatoid arthritis in Traditional Chinese Medicine.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  All rats were randomly divided into five groups: normal control, CIA, dexamethasone, 15mg/kg and 30mg/kg GMI.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Likun
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China. Electronic address: wuyin_2005@126.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China. Electronic address: paperadwen@outlook.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D035264:Flowers / Q000737:chemistry*; D030012:Gentiana / Q000737:chemistry*; D018836:Inflammation Mediators / Q000097:blood; D057888:Iridoid Glucosides / Q000302:isolation & purification / Q000494:pharmacology; D057889:Iridoid Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D057888:Iridoid Glucosides; D057889:Iridoid Glycosides; D039823:Iridoids; D010936:Plant Extracts; C012997:gentiopicroside; C002947:loganic acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C049412:sweroside
keywords: Collagen-induced arthritis; Gentiana macrophylla Pall.; Gentiopicroside; Iridoid glycosides; Rheumatoid arthritis