Metabonomics-Based On Evaluation The Efficacy And Mechanism Of Action Of Ethnomedicine Herba Erigerontis And Fructus Hippophae

Considering the treatment of complex diseases, ethnomedicine has unique comparing with drugs of single chemical composition. However, ethnomedicine's indefinable efficacy and security of modern knowledge and research have led a constriction in its development. It is necessary for us to build up a new mode in the person of the ethnomedicine characteristics, combining system theory and reductionism, summarizing and extracting from the ideas, methods and modes of the efficacy evaluation and mechanism of ethnomedicine.Miao National Herbs Herba Erigerontis and Zang National Herbs Fructus Hippophae are effective drugs which respectively used for prevention and treatment of ischemic stroke and thoracic obstruction. Both of them have a long history as drug and are very important in the ethnomedicine. For example, many Zang National Herbs preparations includes Fructus Hippophae paste.They are also contained by Pharmacopoeia of China and have a high market share.Material basis for efficacy of them is the active ingredients flavonoids which have proved to be obvious therapeutic for cardiovascular and cerebrovascular diseases. Therefore, reseaching Miao National Herbs Herba Erigerontis and Zang National Herbs Fructus Hippophae as examples have better representation and application of the value.ObjectiveUnder the guidance of ethnomedicine theory, combining systems chemical biology's idea and metabonomics's method, we chose Miao National Herbs Herba Erigerontis and Zang National Herbs Fructus Hippophae as our research targets, which are well known in curing ischemic apoplexy and cardiac obstruction respectively. Through the research, we attempt to establish a new method of efficacy evaluation and mechanism of action on prevention and treatment of cardiovascular and cerebrovascular diseases using ethnomedicine.MethodsWe carried on Miao National Herbs Herba Erigerontis and Zang National Herbs Fructus Hippophae's pharmacodynamics research separately by two models, which were focal cerebral ischemia-reperfusion models in rats, induced by the transient occlusion of the middle cerebral artery (MCAO) using fishing line and induced the rats into acute syndrome of blood stasis using epinephrine and ice water. At the same time, based on UPLC-Q TOF/MS and the pattern recognition technology of PCA, PLS-DA and so on, we have researched how it effected the metabolic profiles of model rats by its urine analysis before and after making the mold and administiting medicine. Thus we could study the efficacy evaluation and mechanism of action of ethnomedicine using metabonomics.Results(1) Pharmacodynamics researchHerba Erigerontis can significantly reduce the cerebral infarction area, improves the histomorphology changes in rat brain and promote the number of Nissl's Body increase, and the reason possibly is through the reduction of apoptosis promoter of Bax to express weakly in brain seahorse area nerve cell, thus displaying brain protective function. Herba Erigerontis can also promote neuroethology restoration ahead of time obviously.The results of various index suggest that the dose-effect relationship is irregularity, and the effect is from strong to weak as follows:Low dose, high dose, middle dose.Extractive of Fructus Hippophae can reduce the acute syndrome of blood stasis rats's blood stickiness and RBC density obviously, weaken the RBC aggregation ability and blood coagulation ability, improves hemorheology of pathologic status, such as "thick, stick, coagulation, aggregation". The effect is obviously with Low dose and high dose.(2) Metabonomics-based on evaluation the efficacyHerba Erigerontis injection and extractive of Fructus Hippophae can help model rats's metabonomics return to the control, and the effect is from strong to weak as follows:Low dose, high dose, middle dose.(3) Metabonomics-based on research the mechanism of actionHerba Erigerontis could partially relieve or entirely inhibit the effect of external stimulating factor "the transient occlusion of the middle cerebral artery (MCAO) using fishing line" to the body.The mechanism of action of Herba Erigerontis may be related to potential biomarkers, such as kynurenic acid, N2-succinyl-L-ornithine, and L-leucyl-L-proline.They also possibly participate in the metabolic pathway of "the tryptophan-kynurenic acid"and "succinyl ornithine-urea cycle-NO".Extractive of Fructus Hippophae could partially relieve or entirely inhibit the effect of external stimulating factor "epinephrine and ice water" to the body.The mechanism of action of extractive of Fructus Hippophae may be related to potential biomarkers, such as L-Phenylalanine, L-Tryptophan, N2-succinyl-L-ornithine, kynurenic acid, 3,7-Dihydroxy-12-oxocholanoic acid, cholic acid. They also possibly participate in the metabolic pathway of "the phenylalanine-tyrosine-catecholamines", "the tryptophan-5-hydroxy tryptamines", "succinyl ornithine-urea cycle-NO" and "the cholesterol-bile acid".ConclusionThis study primarily demonstrates the efficacy evaluation and the mechanism of action of Miao National Herbs Herba Erigerontis and Zang National Herbs Fructus Hippophae using metabolimics and its consistency with pharmacodynamics research.The metabonomics study discovered some potential biomarkers and the metabolic pathways that ethnomedicine regulates, and enriched the mechanism of action research for ethnomedicine.In addition this study has promulgated the essential biochemistry material base of the acute syndrome of blood stasis. Therefore, metabonomics is very valuable as to be a new choice as evaluating the efficacy and studying the mechanism of action of ethnomedicine, which expanded the modern research mentality of ethnomedicine.Innovation(1) This study primarily discovered some potential Biomarkers and the metabolic pathway related with MCAO rats and Herba Erigerontis.(2)This study not only discovered that the basis of biochemistry substances of the acute syndrome of blood stasis were series of potential biomarkers, but also expatiated how extractive of Fructus Hippophae influenced on it. (3)This study explored a new method to evaluate the efficacy by combination Metabolomics with Pharmacodynamics.