| Mi Jian Chang Pu Dectotion(MJCPD)is a well-known Hui Medicine formula in ?Huihui Medicine Formulary?,composed of Crocus sativus L.and Acorus tatarinowii Schott.It can invigorate spleen and activate blood circulation,as well as remove blood stasis.MJCPD can improve the hemiplegia,deviation of the eye and mouth,language dysfunction and other symptoms caused by the stroke.Modern pharmacological and clinical experimental data showed that MJCPD has a good promoting effect on hemiplegia after stroke and improvement of language function.The paper studied MJCPD by combining chemomics with metabonomics through the LC-MS.The aim of this paper is to explore the pharmacodynamic material basis and mechanise,so as to provide reference for the study of other traditional Chinese medicine prescriptions.An UPLC-QTOF-MS method was applied to isolate and elucidate chemical constituents in MJCPD and rat serum and brain after oral administration.24 prototype components were identified by database matching and secondary fragment ions.7 of them originated from Crocus sativus L.and 17 from Acorus tatarinowii Schott,including volatile substances,terpenoids and organic acid compoundst.After oral administration normal rats and MCAO model rats of MJCPD,8 components in serum were identified by Crocus sativus L.,including 4 prototype ingredients(crocetin,crocusatin I,crocusatin K and crocusatin)and 4 new ingredients(sitosterol,safranal,3-hydroxy-4-methoxybenzoic acid and crocusatin G).It is presumed that the compatibility of Crocus sativus L.and Acorus tatarinowii Schott produced new components or metabolic components to enter the blood.At the same time,we identified its brain-entry components.The data showed that 6 components were detected in normal rats and 7 components were detected in OVX rats.Compared with Crocus sativus L.single ingredients,only 3 components(crocetin,crocusatin G and crocusatin H)entered brain with prototype components,and produced 7 new components.The results showed that Acorus tatarinowii Schott can pormote Crocus sativus L.into blood and brain,further illustrate the compatibility effect of MJCPD on the basis of chemical substances.The results was an offer of assistance for the metabolism and quality control of MJCPD.A metabonomic approach based on the UPLC-QTOF-MS has been developed to characterize the global serum metabolic profile assocoated with ischemic stroke and explored the intervention mechanisms of MJCPD.40 potential serum biomarkers for cerebral ischemia were screened and 11 endogenous metabolites were identified according to the standards test.It mainly includes isofraxidia,benzoic acid,3-methylindole,salsolinol,tryptophan,vedaprofen,4-hydroxybenzoic acid-n-butylester,stearic acid,pantothenic acid,methyl jasmonate,and 1-myristoyl-2-hydroxy-sn-3-PC as beening involved in pantothenate and coenzyme A biosynthesis,aminoacyl-t RNA biosynthesis,amino acid metabolism,tryptophan metabolism,ketone synthesis and degradation pathways.The results showed that MJCPD administration could provide satisfactory effects on ischemic stroke through regulating the metabolic pathways.Finally,the PLS-DA diagram of different metabolites demonstrated that Crocus sativus L.has synergistic effect after compatibility with Acorus tatarinowii Schott.A tissue-untargeted metabonomic method using UPLC-QTOF-MS was developed to characterize the metabolic profile of MCAO-induced cerebral ischemia in rats for comprehensive metabonomic analysis.21 endogenous biomarkers were preliminarily screeded through multivariate statistical analysis under the positive and negative ion mode.It was confirmed that MJCPD has satisfactory effects on MCAO-induced cerebral ischemia from the regulation pattern of metabolites.MJCPD administration could provide satisfactory effects on MCAO-induced cerebral ischemia through regulating the related metabolic pathways including amino acid metabolism,sugar degradation,tricarboxylic acid cycle,which could help us to enaluate the mechanism of MJCPD in protected ischemic stroke.The results of this study showed that the PLS-DA scoring map of tissue differential metabolites were consistent with those of serum metabolites,which further demonstrated that the treatment effect of Crocus sativus L.combined with Acorus tatarinowii Schott was better than that of single drug,as well as had synergistic effect.It provided a new methodological way for studying the whole pharmacodynamic action of other traditional Chinese medicine.Based on the above chemical substance basis,in vivo overall animal pharmacodynamics and metabolomics results,it is indicated that the combination of MJCPD could pormote saffron glycoside active ingredients to enter the blood and brain,so as to achieve the pharmacodynamic effect of preventing and treating ischemic stroke.From the perspective of metabolomics,it is the compound that can synergistically regulate the metabolic markers of ischemic stroke,making it closer to the normal level than the single-flavored drug,thus achieving synergistic effect. |
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