Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol-induced gastric ulcer in vitro and in vivo

Author:

Wang Kun-Teng1,Chen Lih-Geeng2,Wu Chih-Hsiung3,Chang Chun-Chao4,Wang Ching-Chiung1

Affiliation:

1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

2. Graduate Institute of Biomedical and Biopharmaceutical Sciences, College of Life Sciences, National Chiayi University, Chiayi, Taiwan

3. Division of General Surgery, Department of Surgery, Taipei Medical University and Hospital, Taipei, Taiwan

4. Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

Abstract

Abstract Objectives The rhizome of Atractylodes ovata De Candolle is popularly used in traditional Chinese medicine to treat gastrointestinal diseases. However, the major gastroprotective compounds of A. ovata have not been identified. This study reports on the principal gastro- protective component of A. ovata. Methods Five sesquiterpenoids (atractylon, atractylenolides I, II, III and biatractylolide) were isolated from the extracts of A. ovata rhizome via silica gel column chromatography. The gastroprotective effects of these five sesquiterpenoids were measured in in-vitro ethanol-induced primary culture rat gastric mucosal (PRGM) cell damage and in-vivo ethanol-induced acute rat gastric ulcer models. Key findings Atractylon, atractylenolide I and biatractylolide were strongly toxic in PRGM cells, whilst atractylenolides II and III were not. Atractylenolide II did not show cytoprotective effects, but oral administration of atractylenolide III dose-dependently prevented ethanol-induced PRGM cell death and cell membrane damage. The EC50 values were 0.27 and 0.34 mm, respectively. In the in-vivo assay, atractylenolide III 10 mg/kg significantly reduced 70% ethanol-induced Wistar rat gastric ulcer. Atractylenolide III could inhibit matrix metalloproteinase (MMP)-2 and MMP-9 expression through upregulation of tissue inhibitors of metalloproteinase from the gastric ulcerated tissues. Conclusions Atractylenolide III was the major gastroprotective component of A. ovata in ethanol-induced acute gastric ulcer. It is suggested that the gastroprotective mechanism of atractylenolide III was via inhibition of the MMP-2 and MMP-9 pathway.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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