TY - JOUR
T1 - Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol-induced gastric ulcer in vitro and in vivo
AU - Wang, Kun Teng
AU - Chen, Lih Geeng
AU - Wu, Chih Hsiung
AU - Chang, Chun Chao
AU - Wang, Ching Chiung
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Atractylenolide III
KW - Atractylodes ovata
KW - Matrix metalloproteinases
KW - Primary culture rat gastric mucosal cells
KW - Tissue inhibitors of metalloproteinase
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U2 - 10.1211/jpp.62.03.0014
DO - 10.1211/jpp.62.03.0014
M3 - Article
C2 - 20487223
AN - SCOPUS:77950286406
SN - 0022-3573
VL - 62
SP - 381
EP - 388
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 3
ER -