Study On The Chemical Constituents Of The Phenols In The Ethnic Medicine Radix

Thymus quinquecostatus Celak belongs to the genus thymus of Lamiaceae family,which the dry aerial part used as the medicin.It can dispel wind and relieve exterior,activate vital energy and eliminate pain by traditional Chinese medicine theory.The recent reports about T.quinquecostatus were mainly focused on chemical constituents and pharmacological of its essential oils,and the non-volatile part was rare researched.The previous work on the subject studid that five different polar fractions of T.quinquecostatus antioxidant activities were evaluated by ABTS and DPPH free radical scavenging assays,and they all showed strong scavenging actions,wherein the ethyl acetate and n-butanol fractions showed the best free radical scavenging capacity.Cytotoxic effect on human gastric cancer BGC-823 cells of five different polar fractions of T.quinquecostatus was also tested,ethyl acetate and n-butanol parts being significantly inhibitory effect on human gastric cancer BGC-823 cells.The experimental group was first isolated flavonoids and phenolic acid from T.quinquecostatus.These ingredients in clinical as medicine treat for a variety of cardiovascular and cerebrovascular diseases with significant therapeutic effect,but so far non-volatile parts related pharmacological research has not been reported.The research group then pre-experiment using mice with cerebral ischemia-reperfusion model,investigated ethanol extracts of T.quinquecostatus(rich in flavonoids and phenolic constituents)on cerebral ischemia range by TTC staining.Results showed that ethanol parts gavage three days,can significantly reduce the infarct scope of cerebral ischemia-reperfusion model small mouse(model group,15.43±1.9%;T.quinquecostatus group 20 g/kg,5.03±1.6%;P<0.01),suggesting the ethanol of T.quinquecostatus might have the have anti-ischemic cardio-cerebral diseases.Therefore,to clarify T.quinquecostatus played efficacy material basis,it is very importance to study the non-volatile active components.Part I Literature ReviewIn this paper,137 domestic and foreign literatures on the thymus genus plants,Thymus genus of polyphenolic chemical constituents and pharmacological activities aspects of literature were consolidated and summarized,which can provide reference for further study and development of the genera plants.T.quinquecostatus is one of the most important genus belongs thymus,and its extracts was reported to have good anticancer and antioxidant effects.Our group obtained 19 compounds from T.quinquecostatus,including scutellarin and scutellarein with great biological activities which were first time isolated from thymus genus.Therefore,national drug T.quinquecostatus related research applications were reviewed in the paper,and the source,distribution and preparation and detection method of scutellarin and scutellarein the higher contents in T.quinquecostatus were also reviewed for further exploitation providing a theoretical basis.Part II Study on the chemical constituents of T.quinquecostatus Celak19 compounds were isolated from the aerial parts of T.quinquecostatus.The chemical structures were identified by spectral analysis including MS and NMR spectrometers,and by the comparison of spectroscopic data with the reported values in the literatures.The components isolated from T.quinquecostatus were main polyphenol,a total of 14,including a quinone ingredient:T.quinquecostatus quinone A(1);five phenolic compounds:T.quinquecostatus glycosides A(2),rosmarinic acid(3),p-hydroxy-cinnamic acid(4),caffeic acid(5),ferulic acid(6);eghit flavonoids:scutellarin(7),scutellarein(8),xanthomicrol(9),5,6,7-trihydroxy-4’-methoxy flavone(10),4’-methoxy-luteolin(11),luteolin(12),apigenin(13),rutin(14);others including three triterpenoids:α-amyrin(15),ursolic acid(16),oleanolic acid(17);two sterols:β-sitosterol(18)and daucosterol(19).T.quinquecostatus quinone A(1)and T.quinquecostatus glycosides A(2)are two new compounds;5,6,7-trihydroxy-4’-methoxy flavone(10)was the first time isolated from the genus;p-hydroxy-cinnamic acid(4),caffeic acid(5),ferulic acid(6),xanthomicrol(9),4’-methoxy-luteolin(11)were isolated from the plants for the first time.The above compounds enriched type of structure of the chemical composition separated from T.quinquecostatus.T.quinquecostatus quinone A(1)having five-membered rings oxygen heterocycles,according to the literatures,with the segment of the naphthoquinone compounds being not reported,is the new frame compound.T.quinquecostatus glycosides A(2)has not been reported with different substituting and different substituent positions on the benzene ring compared to 2,4dihydroxy-5-isobutyl-β-D-glucopyranoside.Cesternosides A as a new single-glycoside compound isolated from Cestrum nocturnum,the compound has reported to having antioxidant and anti-inflammatory effects,suggesting that T.quinquecostatus glycosides A(2)has the same biological activities.Scutellarin(7)and scutellarein(8)has been found good efficacy for the treatment of cerebral insufficiency,cerebral hemorrhage caused complications,hyperviscosity hyperlipidemia,cerebral thrombosis,coronary heart disease and angina and other cardiovascular diseases in clinics.Xanthomicrol(9)was reported to inhibit platelet aggregation,anti-oxidation,anti-inflammatory,anti-cancer and other pharmacological activity,with broad application prospects.It is worth mentioning that high levels of oleanolic acid and ursolic acid were found in T.quinquecostatus.Researches has reported that ursolic and oleanolic acid can enhance the antidiabetic drugs rosiglitazone hypoglycemic,lipid-lowering effect,also enhanced the effect of statin drugs.Triterpenoids found in the plant and coumpands 7-9 provides a theoretical basis to elucidate T.quinquecostatus playing effective substance basis of anti-cardiovascular disease.Innovation point:1.Two new compounds were separated from the non-volatile part of T.quinquecostatus.T.quinquecostatus quinone A(1)is the new naphthoquinone skeleton.T.quinquecostatus glycosides A(2)having different substituents and different substituent positions in the benzene ring,is a new phenolic glucopyranoside.2.5,6,7-trihydroxy-4’-methoxy flavone(10)was the first time isolated from the genus.3.P-hydroxy-cinnamic acid(4),caffeic acid(5),ferulic acid(6),xanthomicrol(9),4’-methoxy-luteolin(11)were isolated from the plants for the first time.4.4’,5-dihydroxy-6,7,8-trimethoxy flavone(9)is a multi-methoxylated flavone,and has significant pharmacological effects such as inhibition of platelet aggregation,anti-oxidation,anti-inflammatory and anti-cancer activities.