[关键词]
[摘要]
目的 探究抽薹后的白花前胡叶水提物急性毒性和对小鼠便秘的改善作用机制。方法 将 40 只 ICR 健 康小鼠(雌雄各半)随机分为 2 组:对照组、抽薹后的白花前胡叶水提物组 (简称“白花前胡叶组”),一次性 给予最大剂量抽薹后的白花前胡叶水提物灌胃,评价小鼠急性毒性作用。将小鼠分为 4 组:正常组、模型组、 白花前胡叶高剂量组、白花前胡叶低剂量组,采用洛哌丁胺诱导小鼠便秘模型,给予抽薹后的白花前胡叶水提 物干预 16 d,测定粪便含水率、4 h 粪便粒数以及小肠墨汁推进率等指标评价其改善便秘作用;收集小鼠粪便, 采用 16S rRNA 测序检测肠道菌群的多样性和组成变化。结果 抽薹后的白花前胡叶水提物在小鼠急毒实验中 表现出较高的安全性。在毒性试验中,小鼠小肠指数出现显著下降(P<0.05,P<0.01),给药组小鼠发生轻微 腹泻,推测抽薹后的白花前胡叶水提物能够促进小肠蠕动。小鼠便秘实验结果显示,抽薹后的白花前胡叶水 提物显著改善便秘导致的小鼠粪便含水率(P<0.05,P<0.01)、增加 4 h 粪便粒数(P<0.01)及提高小肠推 进率(P<0.001,P<0.05)等症状。16S rRNA 测序结果显示,抽薹后的白花前胡叶水提物能够显著改变洛哌丁 胺诱导的便秘小鼠肠道微生物的多样性和组成,降低放线菌门的丰度以及厚壁菌门和拟杆菌门的比例,增加双 歧杆菌丰度值。此外,超高效液相色谱-四级杆-静电场轨道阱串联质谱(UHPLC-QE-MS)分析结果显示抽薹后 的白花前胡叶中主要化学成分与其根相似度较高。结论 抽薹后的白花前胡叶水提物对洛哌丁胺诱导的小鼠便 秘具有显著改善作用,安全有效,无明显毒副作用,具有开发利用价值。
[Key word]
[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.
[中图分类号]
R285.5
[基金项目]
国家“十四五”重点研发计划课题(2023YFC3503804);国家自然科学基金青年项目(32202442)。