甘草对雷公藤甲素与雷公藤内酯酮体内代谢成分的影响

目的:研究甘草对雷公藤甲素与雷公藤内酯酮体内代谢成分的影响.方法:采用LC-MS/MS研究雷公藤甲素和雷公藤内酯酮单独给药及与甘草联合给药后在大鼠血浆中相应代谢成分,比较单独给药及联合给药后代谢产物种类和生成量的差异.结果:在雷公藤甲素单独给药组及其与甘草联合给药组的大鼠血浆中,均发现4个代谢产物:m/z([M+H]+)359,359,375,377,其中羟基氧化代谢产物(m/z359)生成量较大.在雷公藤内酯酮单独给药组及其与甘草联合给药组的大鼠血浆中,均发现代谢产物3个:m/z([M +H]+)375,397,413,其中羟基化代谢产物(m/z 375)生成量较大,在联合给药组的大鼠血浆中还发现1个单独给药组中没有的代谢产物m/z([M +H]+)413.联合给药组比单独给药组的各代谢产物生成量大.结论:雷公藤甲素和雷公藤内酯酮单独给药及其与甘草联合给药后,大部分代谢产物相同,其中氧化代谢产物为主要代谢产物.甘草可加速雷公藤甲素和雷公藤内酯酮的体内代谢,为阐明甘草对雷公藤的减毒增效作用机制提供参考.

Effect of Glycyrrhiza uralensis on in vivo Metabolites of Triptolide and Triptonide

Objective:To investigate effect of Glycyrrhiza uralensis on in vivo metabolites of triptolide and triptonide,disclose attenuation mechanism of G. uralensis on Tripterygium wilfordii. Method:SD rats were divided into single and combined administration groups.Combined groups were injected with triptolide or triptonide after orally treated with extracts of G. uralensis,while these single groups was injected only with triptolide or triptonide. Metabolites of triptolide or triptonide in rat plasma were identified and determinated by LC-MS/MS,and compared difference of metabolites under two administration models. Result:Four metabolites ([M+H]⁺,m/z 359,359,375,377) of triptolide and three metabolites ([M+H]⁺,m/z 375,397,413) of triptonide in rat plasma were found under two administration models,respectively;Oxydation metabolites (m/z 359 of triptolide,m/z 375 of triptonide) were the major metabolites.Another metabolite ([M+H]⁺,m/z 413) of triptonide in rat plasma were found only in these combined administration groups.Difference of the amount of metabolites under two administration models was significant,combined administration model was the larger. Conclusion:Under two administration models,most of metabolites of triptolide and triptonide in rat plasma were the same,while major metabolites was oxidative metabolites.G. uralensis could accelerate in vivo metabolism of triptolide and triptonide,it could provide a reference for clarifying attenuation synergistic mechanism of T. wilfordii.