Zhang Bin, He Xiao-Li, Ding Yi, Du Guan-Hua
National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Eur J Pharmacol. 2006 Jan 13;530(1-2):166-71. doi: 10.1016/j.ejphar.2005.11.030. Epub 2005 Dec 22.
One of the major factors limiting the use of non-steroidal anti-inflammatory drugs is gastrointestinal toxicity. Gaultherin, 2-[(6-O-beta-D-Xylopyranosyl-beta-D-glucopyranosyl)oxy] benzoic acid methyl ester, a natural salicylate derivative extracted from Gaultheria yunnanensis, has been shown to have analgesic and anti-inflammatory effects and lack gastric ulcerogenic effect compared to aspirin in our primary study. The aim of this study was to investigate the mechanism of action of gaultherin, which may rely on its active metabolite, and the mechanism responsible for the non-ulcerogenic property. The results showed that gaultherin (200 mg/kg) significantly inhibited the abdominal contractions in the acetic acid-induced writhing test in mice. The anti-inflammatory effect of gaultherin was demonstrated in the croton oil-induced ear edema model in mice. The results showed that gaultherin and equimolar dose of aspirin produced comparable inhibitory effects. The study of the metabolism characters of gaultherin in mice and rats indicated that gaultherin could be metabolically converted to salicylate, which produced the pharmacological effects, and provided effective concentrations for an extended period. In vitro metabolism experiment showed that gaultherin was metabolized by beta-glycosidase produced by human intestinal bacteria and esterases in intestine, blood and liver successively to release salicylate finally. The study suggested gaultherin did not cause gastric ulcer for the reason that it released salicylate in intestine slowly, not in stomach and it left the cyclooxygenase-1 unaffected, which was the source of cytoprotective prostaglandins in gastric epithelium.
限制非甾体抗炎药使用的主要因素之一是胃肠道毒性。冬绿苷，即2-[(6-O-β-D-吡喃木糖基-β-D-吡喃葡萄糖基)氧基]苯甲酸甲酯，是从滇白珠中提取的一种天然水杨酸盐衍生物，在我们的初步研究中已显示出具有镇痛和抗炎作用，且与阿司匹林相比缺乏致胃溃疡作用。本研究的目的是探究冬绿苷的作用机制，其可能依赖于其活性代谢产物，以及探究其不产生溃疡的特性的机制。结果表明，冬绿苷（200毫克/千克）在小鼠醋酸诱导的扭体试验中显著抑制腹部收缩。冬绿苷的抗炎作用在小鼠巴豆油诱导的耳水肿模型中得到证实。结果表明，冬绿苷和等摩尔剂量的阿司匹林产生了相当的抑制作用。对冬绿苷在小鼠和大鼠体内代谢特征的研究表明，冬绿苷可代谢转化为水杨酸盐，后者产生药理作用，并能在较长时间内提供有效浓度。体外代谢实验表明，冬绿苷先后被人肠道细菌产生的β-糖苷酶以及肠道、血液和肝脏中的酯酶代谢，最终释放出水杨酸盐。该研究表明，冬绿苷不会导致胃溃疡，原因是它在肠道而非胃中缓慢释放水杨酸盐，且不会影响环氧化酶-1，而环氧化酶-1是胃上皮细胞保护前列腺素的来源。
