Gastroprotective and safety effects of WIN-34B, a novel treatment for osteoarthritis, compared to NSAIDs |
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Authors: | Huh Jeong-Eun Lee Won-Il Seo Byung-Kwan Baek Yong-Hyeon Lee Jae-Dong Choi Do-Young Park Dong-Suk |
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Institution: | a Oriental Medicine Research Center for Bone & Joint, Disease Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea b Department of Acupuncture & Moxibustion, East-West Neo Medical Center, Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea c Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University, 1 Hoegidong, Dongdaemungu, Seoul 130-701, Republic of Korea |
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Abstract: | Ethnopharmacological relevanceThe 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.ObjectiveTo 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.Materials and methodsTo investigate acute toxicity, we orally administered a single dose of 5000 mg/kg WIN-34B to rats. To investigate chronic toxicity, we orally administered 500, 1000 or 2000 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 2000 mg/kg), diclofenac (10, 40, or 80 mg/kg), celecoxib (100 or 1000 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 E2 (PGE2) and leukotriene B4 (LTB4). 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.ResultsWIN-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 LTB4 synthesis while both diclofenac and celecoxib increased LTB4 synthesis. WIN-34B slightly reduced PGE2 production, while both diclofenac and celecoxib significantly reduced PGE2 production. In a rat model of diclofenac-induced gastric injury, WIN-34B significantly suppressed LTB4 synthesis and restored PGE2 release.ConclusionsThese 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 PGE2 and LTB4. |
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Keywords: | Lonicera japonica Thunb Anemarrhena asphodeloides Bunge Gastric ulcer Prostaglandin E2 Leukotriene B4 |
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