title: The therapeutic effects of Periploca forrestii Schltr. Stem extracts on collagen-induced arthritis by inhibiting the activation of Src/NF-κB signaling pathway in rats.
abstract: BACKGROUND
  Periploca forrestii Schltr. is a classical traditional Chinese medicine (TCM) called Heilonggu (HLG) in China. According to the theory of TCM, it possesses the efficacy of eliminating wind and removing dampness. In clinical practice, it is commonly used for the treatment of rheumatoid arthritis. The present work aimed to evaluate the anti-rheumatism activity of HLG ethanol extract and reveal the underlying molecular mechanism by employing an animal model of collagen-induced rheumatoid arthritis (CIA) in rats.
  
  
  METHODS
  The CIA was induced in male Sprague-Dawley rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of HLG (200 and 400mg/kg) from day 1, with the treatment lasting for 28 days. A variety of indicators were measured for evaluation of anti-rheumatism effect, including paw swelling, arthritis scores, and histopathological changes. Furthermore, the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2), nuclear factor NF-κB p65 and Src kinase in joint synovial tissues were detected to explore the possible mechanisms.
  
  
  RESULTS
  The administration of HLG significantly restored type II collagen-induced arthritis in rats as evidenced by decrease in paw swelling and inflammatory factors in serum. Meanwhile, this treatment also notably reduced NF-κB p65 and COX-2 expression. Surprisingly, the activity of Src kinase was also inhibited demonstrated by downregulation of phosphorylated Src.
  
  
  CONCLUSIONS
  Our results revealed that HLG possessed observable therapeutic action on collagen-induced arthritis by inhibiting the activation of Src and nuclear translocation of NF-κB in rats. HLG may serve as a potential candidate for the management of patients with RA.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ke
authors.affiliation: Key Laboratory of Biomedical Functional Meterials, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Key Laboratory of Biomedical Functional Meterials, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomedical Functional Meterials, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: fengfeng@cpu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: iuwenyuan8506@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D016391:Genes, src / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000187:drug effects*; D031109:Periploca / Q000737:chemistry / Q000633:toxicity; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity; D018547:Plant Stems / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
keywords: Nuclear factor-κB, Src; Periploca forrestii Schltr; Rheumatoid arthritis