中药新药与临床药理2025,Vol.36Issue(5):703-717,15.DOI:10.19378/j.issn.1003-9783.2025.05.006
抽薹后的白花前胡叶水提物改善洛哌丁胺诱导的小鼠便秘的作用机制及安全性评价
Mechanism and Safety Evaluation of the Aqueous Extract form Bolting Peucedanum praeruptorum Dunn Leaves in Improving Loperamide-Induced Constipation in Mice
摘要
Abstract
Objective To investigate the acute toxicity of bolting Peucedanum praeruptorum Dunn(PPD)leaf aqueous extract and its mechanism in alleviating constipation in mice.Methods Forty healthy ICR mice(half male and half female)were randomly divided into two groups:a control group and a PPD leaf aqueous extract treatment group.The maximum volume of the aqueous extract was administered via gavage to evaluate acute toxicity.Mice were divided into four groups:a normal group,a model group,a high-dose PPD leaf aqueous extract group,and a low-dose PPD leaf aqueous extract group.A Loperamide-induced constipation model was established,and the PPD aqueous extract was administered for 16 days.Parameters such as fecal water content,4-hour fecal pellet count,and small intestinal propulsion rate were measured to assess its anti-constipation effects.Fecal samples were collected,and 16S rRNA sequencing was performed to detect changes in gut microbiota diversity and composition.Results The aqueous extract of PPD leaves demonstrated high safety in the acute toxicity test.In the toxicity experiment,a significant decrease in the small intestinal index was observed(P<0.05,P<0.01),and mild diarrhea occurred in the treatment group.It was speculated that the aqueous extract of PPD leaves could promote small intestinal motility,which was confirmed by the increased small intestinal ink propulsion rate(P<0.01).The constipation experiment results showed that the aqueous extract significantly improved fecal water content(P<0.01,P<0.05),increased the 4-hour fecal pellet count(P<0.01),and enhanced the small intestinal propulsion rate(P<0.001,P<0.05)in constipated mice.16S rRNA sequencing revealed that the aqueous extract significantly altered the diversity and composition of gut microbiota in Loperamide-induced constipated mice,reducing the abundance of Actinobacteria and the ratio of Firmicutes to Bacteroidetes while increasing the abundance of Bifidobacterium.Additionally,UHPLC-QE-MS analysis indicated that the main chemical components of PPD leaves were highly similar to those of its roots.Conclusion The aqueous extract of PPD leaves significantly alleviates Loperamide-induced constipation in mice,demonstrating safety,efficacy,and no obvious toxic side effects,indicating its potential for development and utilization.关键词
白花前胡叶/抽薹/水提物/洛哌丁胺/急性毒性/肠道蠕动/便秘/肠道菌群/安全性/小鼠Key words
Peucedanum praeruptorum Dunn leaf/bolting/aquecus extract/Loperamide/acute toxicity/intestinal motility/constipation/gut microbiota/safety evaluation/mice分类
医药卫生引用本文复制引用
李岩,孙朝跃,殷齐慧,李国辉,韩邦兴,刘东,赵群,陈存武..抽薹后的白花前胡叶水提物改善洛哌丁胺诱导的小鼠便秘的作用机制及安全性评价[J].中药新药与临床药理,2025,36(5):703-717,15.基金项目
国家"十四五"重点研发计划课题(2023YFC3503804) (2023YFC3503804)
国家自然科学基金青年项目(32202442). (32202442)