School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
J Pharm Pharmacol. 2010 Mar;62(3):381-8. doi: 10.1211/jpp.62.03.0014.
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.
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.
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.
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.
白术的根茎在传统中药中被广泛用于治疗胃肠道疾病。然而，白术的主要胃保护化合物尚未被确定。本研究报告了白术的主要胃保护成分。
通过硅胶柱层析从白术根茎提取物中分离出五种倍半萜（苍术酮、苍术内酯 I、II、III 和倍半苍术内酯）。通过体外乙醇诱导的原代培养大鼠胃黏膜（PRGM）细胞损伤模型和体内乙醇诱导的急性大鼠胃溃疡模型，测定这五种倍半萜的胃保护作用。
苍术酮、苍术内酯 I 和倍半苍术内酯在 PRGM 细胞中具有很强的毒性，而苍术内酯 II 和 III 则没有。苍术内酯 II 没有表现出细胞保护作用，但苍术内酯 III 的口服给药可剂量依赖性地预防乙醇诱导的 PRGM 细胞死亡和细胞膜损伤。EC50 值分别为 0.27 和 0.34mm。在体内试验中，苍术内酯 III 10mg/kg 可显著减少 70%乙醇诱导的 Wistar 大鼠胃溃疡。苍术内酯 III 可通过上调胃溃疡组织中的金属蛋白酶抑制剂，抑制基质金属蛋白酶（MMP）-2 和 MMP-9 的表达。
苍术内酯 III 是白术在乙醇诱导的急性胃溃疡中的主要胃保护成分。提示苍术内酯 III 的胃保护机制可能是通过抑制 MMP-2 和 MMP-9 途径。
