摘要
目的明确防己黄芪汤(Fangji Huangqi Tang,FHT)改善脾虚肾性水肿的药效,并筛选确定其活性相态。方法采用梯度离心-透析法对FHT各相态进行拆分,通过物相多尺度表征手段对各相态进行理化分析。建立脾虚肾性水肿小鼠模型进行药效评价,结合主成分分析(principal component analysis,PCA)构建综合药效指标以筛选活性相态。结果FHT通过梯度离心-透析法拆分为真溶液相(true solution phase,TSP)、胶体相(colloidal phase,CP)、混悬相(suspension phase,SP)和沉淀相(precipitate phase,PP)4个相态。理化分析显示各相态在盐度(salinity,SAL)、总溶解固体(total dissolved solids,TDS)、电导率(electrical conductivity,EC)和pH值等方面存在显著差异;LC-MS分析共鉴定105个化合物,PP含102个,包括黄芪黄酮、防己碱等特征成分。药效研究表明,FHT能显著改善脾虚肾性水肿小鼠的脾虚症状,升高微量白蛋白(microalbumin,m Alb)和水通道蛋白2(aquaporin 2,AQP2)水平,缓解脂代谢紊乱;相态破坏后药效降低,证明相态结构对药效至关重要。各相态对脾虚及肾功能指标均有不同程度改善,综合药效排序为FHT>PP>CP≈阳性药益肾化湿颗粒。结论FHT能有效改善脾虚肾性水肿,PP是其发挥药效的关键活性相态。为FHT治疗肾性水肿提供了科学依据,并为中药复方物质基础研究和纳米药物开发提供了新思路。
Objective To clarify the efficacy of Fangji Huangqi Tang(防己黄芪汤,FHT)in improving spleen deficiency-induced renal edema and screen and identify its active phase state.Methods The gradient centrifugation-dialysis method was employed to separate different phase states of FHT.Physicochemical analysis of each phase was conducted using multi-scale characterization techniques.A mouse model of spleen deficiency-induced renal edema was established for pharmacological evaluation.Principal component analysis(PCA)was integrated to construct a comprehensive efficacy index for screening the active phase state.Results FHT was separated into four phase states via gradient centrifugation-dialysis:true solution phase(TSP),colloidal phase(CP),suspension phase(SP)and precipitate phase(PP).Physicochemical analysis revealed significant differences among the phases in salinity(SAL),total dissolved solids(TDS),electrical conductivity(EC)and pH.LC-MS analysis identified 105 compounds,with the PP containing 102 compounds,including characteristic components such as astragalus flavonoids and tetrandrine.Pharmacological studies demonstrated that FHT significantly alleviated spleen deficiency symptoms in mice with spleen deficiency-induced renal edema,increased microalbumin(mAlb)and aquaporin 2(AQP2)levels,and improved lipid metabolism disorders.The efficacy decreased after phase-state disruption,confirming the critical role of phase-state structure in therapeutic effects.Each phase state exhibited varying degrees of improvement in spleen deficiency and renal function indicators,with the comprehensive efficacy ranking as follows:FHT>PP>CP≈Yishen Huashi Granules(益肾化湿颗粒).Conclusion FHT effectively alleviates spleen deficiency-induced renal edema,with the PP serving as the key active phase responsible for its therapeutic efficacy.This study provides a scientific basis for the use of FHT in treating renal edema and offers new insights for research on the material basis of traditional Chinese medicine compounds and the development of nano-pharmaceuticals.
作者
苏贝贝
卢凯
张鑫渝
秦雪梅
李爱平
SU Beibei;LU Kai;ZHANG Xinyu;QIN Xuemei;LI Aiping(Modern Research Center for Traditional Chinese Medicine,Taiyuan 030006,China;The Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi,Taiyuan 030006,China;School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan 030006,China;Institute of Traditional Chinese Medicine of Shanxi,Taiyuan 030012,China)
出处
《中草药》
北大核心
2025年第22期8175-8187,共13页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(82204595)
国家自然科学基金项目联合基金资助项目(U23A20517)
山西省基础研究计划资助项目(202303021221070)
中国博士后基金(340903)
山西省中医药科技创新工程项目(2025kjzy006)。
关键词
防己黄芪汤
脾虚肾性水肿
药效评价
主成分分析
沉淀相
黄芪黄酮
防己碱
Fangji Huangqi Tang
spleen deficiency-induced renal edema
efficacy assessment
principal component analysis
precipitated phase
astragalus flavonoids
tetrandrine
