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


RESULTS
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.
Wang
Kun-Teng
KT
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Chen
Lih-Geeng
LG
Wu
Chih-Hsiung
CH
Chang
Chun-Chao
CC
Wang
Ching-Chiung
CC
D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D031174:Atractylodes / Q000737:chemistry*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D000897:Anti-Ulcer Agents; D004365:Drugs, Chinese Herbal; D007783:Lactones; D020033:Protein Isoforms; D012717:Sesquiterpenes; D019714:Tissue Inhibitor of Metalloproteinases; C424802:atractylenolide III; D000431:Ethanol; D053505:Matrix Metalloproteinases, Secreted