首页|基于"物质-药代-功效"关联研究桑叶解热质量标志物成药性

基于"物质-药代-功效"关联研究桑叶解热质量标志物成药性

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目的 阐释桑叶解热质量标志物(色氨酸)量效关系、作用机制及体内暴露情况等关键质量属性,基于"物质-药代-功效"关联展开桑叶解热质量标志物成药性研究.方法 以酵母致大鼠发热模型为研究对象,评价色氨酸与其他成分的协同作用,并进行量效关系研究;采用ELISA法对色氨酸干预后大鼠下丘脑进行检测,解析色氨酸解热作用机制;通过UPLC-QQQ-MS技术测定色氨酸的药代动力学行为.结果 与同浓度色氨酸组相比,桑叶超载色氨酸组解热效果没有明显提升;不同浓度色氨酸组中,色氨酸1倍剂量组解热效果明显,解热机制可能与色氨酸抑制下丘脑内体温调节因子PGE2的生成有关.灌胃同剂量色氨酸后,模型组和空白组半小时后血药浓度均达峰值,模型组大鼠的AUC和Cmax显著大于空白组,模型组平均驻留时间大于空白组.结论 与对乙酰氨基酚相比,色氨酸对持续性高热效果更为显著,药动学行为与发热病理状态具有相关性,在发热大鼠体内暴露量增加,生物利用度提高,为其后续新药高质量研发提供有益参考,也为"物质-药代-功效"关联的中药创新研发思路提供实验依据.
Druggability Study of Antipyretic Quality Maker in Mulberry Leaf Based on the Correlation of"Substance-Pharmacokinetics-Effects"
Objective To elucidate the dose-effect relationship,mechanism of action,exposure and other key quality attributes of anti-pyretic quality markers(tryptophan)of mulberry leaves,and to investigated the druggability of antipyretic quality markers of mulberry leaves based on the correlation of"substance-pharmacokinetic-efficacy".Methods The yeast induced fever model of rats was taken as the research object to evaluate the synergistic effect of tryptophan and other components,and the dose-effect relationship was studied.The hypothalamus of rats after the intervention of tryptophan were detected by ELISA,and the anti-pyretic mechanism of tryptophan was analyzed.Pharmacokinetic behavior of tryptophan was determined by using the UPLC-QQQ-MS technology.Results Compared with the same concentration of tryptophan group,the antipyretic effect of mulberry leaf overload group was not significantly improved.In different concentrations of tryptophan,the anti-pyretic effect was obvious in the one-dose tryptophan group.The anti-pyretic mechanism may be related to the inhibition of tryptophan on the production of thermoregulatory factor PGE2 in the hypothalamus.After gavage with the same dose of tryptophan,the blood concentration of model group and blank group reached the peak half an hour later.The AUC and Cmax of model group were significantly higher than that of blank group,and the average dwell time of model group was higher than that of blank group.Conclusion Compared with acetaminophen,the effect of tryptophan on persistent high fever is more significant.The pharmacokinetic behavior is correlated with the pathological state of fever,and the exposure in the body of fever rats is increased,and the bioavailability is improved,which provides a useful reference for the high-quality research and development of new drugs.It also provides experimental basis for the innovative research and development of traditional Chinese medicine related with"substance-pharmacokinetics-efficacy".

Substance-pharmacokinetics-effectmulberry leafanti-pyretickey quality attributesdruggability

杨菁华、李青、孔晓妮、田雨晴、王亮、郭威

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青岛大学附属山东省妇幼保健院,中医药与临床药学研究中心,国家卫生健康委生育调控技术重点实验室,山东济南 250014

山东中医药高等专科学校 医学系,山东烟台 264199

物质-药代-功效 桑叶 解热 关键质量属性 成药性

国家自然科学基金青年科学基金项目山东省泰山学者青年专家项目山东省重点研发计划项目山东省自然科学基金青年基金山东省中医药科技发展计划项目山东省妇幼保健院专项资金科研课题

82104391tsqn2022113602019GSF108001ZR2016HQ492015-164YJKY2022-021

2024

10.13728/j.1673-6427.2024.03.003

现代中药研究与实践
安徽中医药高等专科学校,

现代中药研究与实践

CSTPCD
影响因子：0.409
ISSN：1673-6427
年,卷(期)：2024.38(3)