Gastroprotective and safety effects of WIN-34B, a novel treatment for osteoarthritis, compared to NSAIDs

Abstract

Ethnopharmacological relevance 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. Materials and methods To 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 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.