| 1.Compatibility of Chinese medicinal preparation is one of the advantages of Traditional Chinese Medicine(TCM)and pharmacy,in recent years,increasingly brought to the attention of the western medicine.Side effects and safety of traditional Chinese medicine has got more and more attention of people.Reports of side effects of Chinese herbal medicine are increasing.The development of Metabonomics technology provides a new way for the modern research of traditional Chinese medicine.Metabonomics technology applied to the traditional Chinese medicine(TCM)syndromes and the traditional Chinese medicine efficacy evaluation aspects will have broad prospects.Zhusha Anshen Wan(ZSASW)is one of the most widely used TCM prescriptions,originally recorded in "Nei Wai Shang Bian Huo Lun"(a medical literature at Yuan dynasty in China).It contains five Chinese medicines:cinnabar(cinnabaris),Coptidis Rhizoma(Coptis chinensis French.),Angelicae Sinensis Radix(Angelica sinensis(oliv.)Diels),uncooked Rehmanniae Radix(Rehmannia glutinosa Libosch.),and honey fried Glycyrrhizae Radix Et Rhizoma(Glycyrrhiza urallensis Fisch.).It has the effects of "sedating the heart,calming the spirit,draining the fire,and nourishing Yang".Modern pharmacology study shows that cinnabar has strong toxicity influence on the liver and kidney of biological organs.Although the dose of cinnabar in ZSASW is 1.8g/day equal to 3.6 times of the maximum limited dose,there is no record on the toxicities of ZSASW and it has still been used in the clinics until now.In this paper,we used metabonomics technology based on nuclear magnetic resonance(NMR)combined with traditional toxicity evaluation technology to study the toxicity of cinnabar contains HgS mineral drugs,to explore the rationality of compound compatibility of cinnabar anshen pills and the influence of various herbs toxicity caused by cinnabar.At the same time,we also did the further research about the influence of metabolites by the main components of Glycyrrhizae Radix and rhizoma coptidis compared with cinnabar.First,we researched the toxicity of cinnabar and zhusha anshen pills of rat urine and serum metabonomics.We analyzed urine and blood samples of nuclear magnetic resonance proton spectrum,established characteristic metabolic spectra using partial minimum square(PLS-DA)statistical analysis methods to analyze the results.Results showed that the score chart of control VS cinnabar,cinnabar VS zhusha anshen pill has good separation effect,suggests that groups the levels of metabolites in rats have obvious change.When samples of three groups of rats compare at the same time,we can observe,the control group is close to the zhusha anshen pill group,but both of control group and zhusha anshen pill group are away from the cinnabar group.In addition,after dosing cinnabar the metabolites in rats urine 2-ketoglutaric acid,citric acid,succinic acid,lactic acid,creatinine,N-oxide trimethylamine and taurine have some change,which suggests cinnabar could cause disorder of energy metabolism in mice,the change of intestinal flora,speculated that cinnabar of hepatorenal damage mitochondrial function is impaired,the Krebs cycle in the process of abnormal metabolites caused by abnormal energy metabolism and glucose,fat and amino acid metabolism.Zhusha anshen pill has obvious recovery action on the metabolite changes.The results intimated that zhusha anshen pills did not show the toxic effects like cinnabar.The results of the serum biochemical indicators and pathological of liver and kidney showed the same tendency.Next,we compared with the toxicities between every single herbs compatibility cinnabar and cinnabar.Coptidis Rhizoma,Angelicae Sinensis Radix,Rehmanniae Radix,fried Glycyrrhizae Radix had certain protective effect on the toxicity induced by cinnabar.However,after compatibility the drug also have some damage on liver and kidney.On this basis,we used two single herbs combination compared with separate dosing cinnabar.And the recovery action of two single herbs combination is stronger than single herb.The most effective compatibility is Rehmanniae Radix combined with fried Glycyrrhizae Radix.There are effects of synergies and antagonism between them.Finally,according to the results of compatibility of single herbs and two single herbs combined with cinnabar,we did the studies on the protective effects of the main composition of Rehmanniae Radix and fried Glycyrrhizae Radix:glycyrrhizic acid,licorice total saponins,total alkali,and berberine.Results show that the protections of the main component are close to the single drug,but not as good as them.From what has been discussed above,this paper mainly expounded the rationality of zhusha anshen pill prescription;verified the toxicity is reduced greatly in zhusha anshen group.The result could promote the modernization of traditional Chinese medicine(TCM);provide a new thought and method to look for new drugs on the kidney detoxification.2.Forsythia suspense(Thunb.)Vahl is one of the genus Forsythia of the Oleaceae family,which have heat-cleaning,detoxiating and eliminating stagnation activities.By using various chromatographic techniques,27 compounds have isolated from the fruits of the flower of the Forsythia suspense(Thunb.)vahl.On the basis of analysis of UV,NMR and MS date and measuring of physic-chemical characters,their structures were elucidated as follows:methyl chlorogenate(1),kaempferol 3-O-?-glucopyranoside(2),2-(3,4-dihydroxyphenyl)-ethyl-O-?-rhamnopyranosyl-(1?6)-2-O-caffeoyl-?-glucopyranoside(3),benzyl-O-?-glucopyranoside(4),kaempferol-3-O-?-glucopyranosyl-a-rhamnopyranoside(5),vanillyl-alcohol-4-O-?-glucopyranoside(6),3-methoxy-allyl-banzene-4-?-xylosyl-(1?6)-?-glucopyranoside(7),Styraxjaponosi de B(8),rhodioloside(9),2-methoxy-3-(3-methoxybenzyl)-4-(3'-4'-dimethoxybenzyl)-y-butyrolactone-4-O-?-glucopyranoside)(10),Quercetin-3-O-?-glucopyranosyl-(1?6)-rhamnopyranoside(11),2-(4'-Hydroxy-3-methoxy-benzyl)-3-(3'-hydroxy-4-methoxybenzyl)butyrolactone(12),2-(3,4-dimethoxybenzyl)-3?-(4'-hydroxy-3'-methoxybenzyl)-?-butyrolactone-4'-O-(?-glucopyranoside)(7),2-(4'-Hydroxy-3'-metho xybenzyl)-3-(3-hydroxy-4'-methoxy-benzyl)butyrolactone(14),Geniposidic acid(15),4-methoxybenzyl-Ethyl-?-glucopyranoside(16),4-hydroxylbenzyl-Ethyl-?-gl ucopyranoside(17),4-carboxyl-benzyl-?-glucopyranoside(18),3-methylbut-3-enyl-6'-O-?-glucopyrano-side(19),3-methylbut-3-enyl-6'-O-(?-glucopyranosyl)-?-glucopyran oside(20)?4-hydroxylbenzyl-Ethyl-?-glucopyranosyl-(1?6)-?-glucopyranoside(21),Quercetin-3-O-?-glucopyranoside(22),2?-hydroxy oleanolic acid(23),oleanolic acid(24),ursolic aldehyde(25),ursolic acid(26),2a-hydroxyoxyursolic acid(27).LQ-10 is a new compound. |
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