| Brucea javanica as one of the Chinese herbs,which is processed from the dried ripe fruits of Brucea javanica(L.)Merr belonging to the Simaroubaceae DC.Family.and it widely distributed in tropical and subtropical regions.Brucea Javanica can clear away heat and detoxify,cut malaria and stop dysentery;external use can corrode warts.Three-negative breast cancer is an invasive breast tumor subtype with high rate of early recurrence,it often accompanied by cancer cell metastasis and poor prognosis.In order to solve the problems of low specificity of quality evaluation and unknown substance of brucea javanica.In this study,anti-triple negative breast cancer activity was regarded as the breakthrough point.The research was carried out systematically and comprehensively based on ingredient identification,active ingredient screening,pharmacokinetics and multi-component content determination,which provide references for quality control and clinical medication of brucea javanica.1 UPLC-Q-TOF/MS combined the piecewise acquisition,mass defect with molecular network were used to rapidly screen complex components and establish the molecular network.The deep learning algorithm of Python language can fast complete the classifiction of massive data,which greatly solves the problem of time-consuming and labor-consuming.Finally,80 compounds were successfully analyzed and identified from brucea javanica extract,including36 known and 21 potential quassinoids.Meanwhile,4 lignans,4 alkaloids,3 organic acids,3terpenoids and 3 flavonoids were also detected and identified from brucea javanica.Among them,the ion fragments and pyrolysis regularity of standard compounds were compared for 5quassinoids and 2 organic acids.This study provided a considerable convenience for the identification of infinitesimal compounds and unknown compounds in Chinese herbal medicine.2 With the help of network pharmacology,the pharmacological mechanism and active components of 50 identified components from brucea javanica against triple negative breast cancer were studied.Network pharmacology studies have shown that cancer,endocrine and hormone related pathways may be the potential pharmacological mechanisms of brucea javanica in the treatment of triple negative breast cancer.In addition,under the guidance of heat-clearing and detoxicating,yadanzioside E,brusatol,bruceantinol and other components may treat Triple Negative Breast Cancer through EGFR,CDK2,MAPK8,MAPK10,SRC,MAPK14,PDPK1.These results displayed that the Traditional Chinese Medicine has the pharmacological characteristics of multiple components,multiple targets and multiple channels.MDA-MB-231 cell assay results showed that brusatol,bruceine A,bruceine D,bruceine E,yadanziolide A,gallic acid,vanillic acid could significantly inhibit the proliferation of MDAMB-231 cells with time and dose-dependent.Ethanol extract and aqueous extract of brucea javanica also showed obvious anti-triple negative breast cancer activity.It provides a new idea for screening of quality marker and quality evaluation of brucea javanica.3 A UPLC-MS/MS method for simultaneous determination of bruceine D and brusatol in rat plasma was established,the pharmacokinetics and tissue distribution of two analytes after dosing of ethanol extract and aqueous extract of brucea javanica were studied.The results showed that the established method was simple and efficient,it could simultaneously determine the contents of bruceine D and brusatol in different biological samples.The pharmacokinetic differences of the two components in the two extracts and the tissue distribution characteristics of components of brucea javanica in breast cancer mice were expounded,which provided clinical basis for the material basis and rational development of brucea javanica.4 The quality standard of brucea javanica based on identification,fingerprint and content was established.Firstly,brucea javanica was authenticated by character description and thin layer chromatogram.A fingerprint method was established for 27 batches of brucea javanica,meanwhile,the contents of gallic acid,yadanziolide A,bruceine D,vannic acid,brusatol and bruceine A were determined.Secondly,the clustering analysis and orthogonal partial least squares-discriminant analysis were used to further study the factors that affect the brucea javanica of different places.The experimental results showed that the basis classification of brucea javanica is the content differences of vanillic acid,gallic acid,bruceine D,brusatol.Finally,considering chemical component content,activity,specificity and influence,bruceine D and brusatol were selected as the indicator components.According to the dry product,the content of bruceine D and brusatol should not be less than 0.0622% and 0.0480%,respectively.It reflected the whole chemical information of brucea javanica and realized the comprehensive quality evaluation of brucea javanica. |
PDF Full Text Request