title: Gastroprotective and safety effects of WIN-34B, a novel treatment for osteoarthritis, compared to NSAIDs.
abstract: BACKGROUND
  The dried flowers of Lonicera japonica, also known as Japanese honeysuckle, and the dried root of Anemarrhena asphodeloides, the component herbs of WIN-34B, are traditionally used in Eastern medicine to treat various inflammatory conditions including arthritis.
  
  
  OBJECTIVE
  To study the acute and chronic toxicities of WIN-34B and to compare its effects on gastric mucosa with those of diclofenac, a widely used NSAID, and celecoxib, a selective COX-2 inhibitor.
  
  
  METHODS
  To investigate acute toxicity, we orally administered a single dose of 5,000 mg/kg WIN-34B to rats. To investigate chronic toxicity, we orally administered 500, 1000 or 2,000 mg/kg WIN-34B to rats daily for 13 weeks. To assess its effects on gastric mucosa, rats received either a single dose or repeated doses of WIN-34B (400, 1000, or 2,000 mg/kg), diclofenac (10, 40, or 80 mg/kg), celecoxib (100 or 1,000 mg/kg), or vehicle, after which samples of gastric mucosa were assessed grossly and histologically. We also measured tissue activity of myeloperoxidase and synthesis of eicosanoids, including prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). To further assess its effects, we administered WIN-34B to rats either intraperitoneally or orally, measured gastric injury scores using a rat model of diclofenac-induced gastric injury, and measured eicosanoid synthesis.
  
  
  RESULTS
  WIN-34B showed no signs of acute or chronic toxicity in terms of general behavior, gross appearance of the internal organs, blood chemistry, or mortality. WIN-34B did not cause significant gastric mucosal damage after single or repeated doses. In contrast, diclofenac and celecoxib both caused gastric damage. In terms of eicosanoid synthesis, WIN-34B significantly suppressed LTB(4) synthesis while both diclofenac and celecoxib increased LTB(4) synthesis. WIN-34B slightly reduced PGE(2) production, while both diclofenac and celecoxib significantly reduced PGE(2) production. In a rat model of diclofenac-induced gastric injury, WIN-34B significantly suppressed LTB(4) synthesis and restored PGE(2) release.
  
  
  CONCLUSIONS
  These results demonstrate that WIN-34B did not cause acute or chronic toxicity in male or female rats. In addition, WIN-34B did not cause significant gastric mucosal damage, instead appearing to protect the mucosa from diclofenac-induced gastric damage through the regulation of PGE(2) and LTB(4).
authors.affiliation: Oriental Medicine Research Center for Bone & Joint, Disease Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Huh
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Lee
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Seo
authors.forename: Yong-Hyeon
authors.initials: YH
authors.lastname: Baek
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Dong-Suk
authors.initials: DS
authors.lastname: Park
mesh_terms: D031403:Anemarrhena / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D035264:Flowers / Q000737:chemistry; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D031239:Lonicera / Q000737:chemistry; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy*; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010936:Plant Extracts; C569023:WIN 34B