| F.aurantii which was commonly used in traditional Chinese medicine as qi-regulating drugs was firstly recorded in the "Shen Nong's Herbal Classic".With slightly cold,bitter,acrid,sour properties.It has efficacies of dispersing chest qi to relieve chest tightness,eliminating food product to relieve fullness.It has been widely used for treating fullness of the chest and epigastrium,abdominal pain,indigestion,phlegm and fluid retention,organ prolapse.Under the guidance of TCM theory,base on hypothesis of nature and flavor which is "one flavor and one nature",F.aurantii as the research object,apply the research methods of resolvability and combinability and sicence technology of Chinese materia medica,pharmacology,chemical pharmacy,etc to it.Simply its nature and flavor science connotation,and characteristics and indications,clear its role as the theoretical basis for clinical medicine.Also verify the hypothesis "one medicine has X flavor and Y nature(Y<X)" for TCM.It would be the new mode and platform for TCM modern study to clarify the scientific connotation and contact,to build the new style for the nature and flavor of TCM.At the same time,it also confirm the medicinal properties can be split sex,can smell combination of the feasibility of the method.1 To summarize documents.(1)Based on consulting systematically from past dynasties' books on nature and flavor of TCM,studying and arranging overall with all books from ancient to present about Medicinal F.aurantii,We understood the nature and flavor of TCM and the denomination,breed variety,and comprehended source textual research,the nature and flavor theory and the current situation in the chemical composition,pharmacologic action,clinical application of F.aurantii and summarized about the nature and flavor theory of TCM and the published study of F.aurantii.(2)In this paper,through a large number of literature review,summary the polysaccharide extraction,separation,purification,structure characterization and biological activity.For polysaccharide macromolecular compounds in orange research with theoretical basis(3)The nature and flavor of TCM has a complex evolution course.Through the retrieval of ancient documents and modern clinical data,we find out how the F.aurantii evolution process,comfirming different understands about the nature and flavor of TCM from different period and different physicians.From the record "bitter,cold" in Sheng Nong's Herbal Classic to "bitter,acrid,micro-cold",and "bitter,pungent,micro-cold" in Tang and Song dynasties to"bitter,pungent,acrid,micro-warm" in Chinese Pharmacopoeia(2010),it experienced the process both“single-flavor" to "multi-flavor" and the evolution of medicinal upheaval process.2 The resolvability research on the nature and flavor material foundation of F.aurantii:In fact,the nature and flavor of TCM marked as not only the function of the TCM,but also the corresponding material base.Modern pharmacology researches showed that the same structure frame of one species of chemical composition may have the same pharmacologic action,Accordingly,This paper considers the kinds of traditional Chinese medicine medicinal material base,the component type and composition of factors such as physical and chemical properties will be orange water decoction split into four components we split the material basis of decoction of Medicinal F.aurantii for 4 groups,which were polysaccharide composition,flavonoids composition,aetherolea composition and alkaloid composition.We applied UPLC-MS,HPLC to the general chemi-characteristic research of the nature and flavor detached composition.The characteristic of this method was holo-composition which was detached uncross in each composition and maintained the type of chemical composition as far as possible.The split method established was scientific and normative which can provide evidence to the resemble research.3 The estimation system of pharmacologic and the ascription research on the nature and flavor of F.aurantii(1)In the nature and flavor is highly generalization and concise of traditional Chinese medicine as the breakthrough point,through textual research and modern literature research materia medica,we use the traditional Chinese way of thinking and induce deduction method,and draw support from modern statistical methods,such as cluster analysis.We establish the nature and flavor-effect-pharmacological indexes correlation of and structure medicinal pharmacology of the nature and flavor evaluation system of F.aurantii.We established the estimated method by means of the core of nature and flavor and the effectiveness evaluation system by the pharmacology indicatrix.The results indicated that F.aurantii enhancement of gastric emptying,anti-gastric ulcer,asthma and phlegm,cholagogue and strengthening spleen.The effect of enhancement of gastric emptying and cholagogue was based on aetherolea composition,alkaloid composition,and the effect of anti-gastric ulcer was based on flavonoids composition,and the effect of analgesia,asthma and phlegm was based on aetherolea composition,alkaloid composition,and the effect of strengthening spleen was based on polysaccharide composition.(2)Through the experimental results indicated that The combination of TCM theory and the ancient records of clinical application of F.aurantii and scientific theories of modern pharmacology,property and flavour of Chemical separation components of belonging.the results are as follows:the flavor and property of polysaccharide composition is bitter and warm,aetherolea composition and alkaloid composition is pungent?bitter and micro-cold,and the Flavonoids composition is bitter,acrid and cold.Based on consulting systematically from past dynasties books on nature and flavor of TCM,studying and arranging overall with all books from ancient to present about F.aurantii,We understood the nature and flavor of TCM and the denomination,breed variety,and comprehended source textual research,the nature and flavor theory and the current situation in the chemical composition,pharmacologic action,clinical application of F.aurantii and summarized about the nature and flavor theory of TCM and the published study of F.aurantii.4 Study on sequential extraction,structure identification and biological activity of F.aurantii polysaccharides(1)Study on separation,purification and antioxidant capacity of F.aurantii polysaccharidesIn this paper selected F.aurantii as raw material,the study founde its physicochemical has a certain "spleen" activity.Through literature review,the present is still in the blank on the study of physicochemical compounds of F.aurantii.So the paper study F.aurantii physicochemical extraction,separation,purification,structure characterization and its biological activity.? Three polysaccharides fractions A,B and C(CALA,CALB and CALC)were acquired from F.aurantii by sequential extraction with cold water,hot water,1.0 M sodium hydroxide solutions,respectively.A series of in vitro antioxidant experiments such as the DPPH radical scavenging activity experiments,hydroxyl radical scavenging activity experiments,superoxide radical scavenging activity experiment,H2O2 scavenging activity experiments,and in 'vivo mice antioxidant experiments were carried to evaluate the three crude polysaccharides have antioxidant activity.The results showed that three kinds of F.aurantii polysaccharides all have anti-oxidant activity,within a certain range with the polysaccharide concentration increased the antioxidant capacity also increased,among three kinds of polysaccharides,CALB has the strongest activity of DPPH radical scavenging.? CALB was isolated and purified by using ion exchange and gel filtration column chromatography,such as weak cation exchange resin and weak anion exchange resin by series connection,ion-exchange cellulose,ion-exchange sepharose gel,and various high-resolution propylene sephadex gel.Four kinds of pure polysaccharide CALB-1,CALB-2,CALB-3,CALB-4 were isolated from CALB.Physicochemical properties were determined that four kinds of monomers without reducible polysaccharides,non-starch material,free of peptides and proteins,amino acids and other impurities.The structure and monosaccharide composition of the four polysaccharides were evaluated by periodate oxidation,Smith degradation combined with UV,FT-IR,HPLC and GC-MS.? Monosaccharide composition was analyzed by pre-column PMP-derivative-HPLC.The results indicated that CALB-1 is an acidic hetero polysaccharides,composed of Man,Rha,Gal UA,Gal and Ara;CALB-2 is an acidic hetero polysaccharides,composed of Rha,GalUA,Gal and Ara;CALB-3 is an acidic hetero polysaccharides,composed of Man,Rha,Glc UA,GalUA,Gal and Ara;CALB-4 is an acidic hetero polysaccharides,composed of Man,Rha,Glc UA,Gal UA,Gal and Ara.Through vitro antioxidant experiments prove that among four kinds of monosaccharide,CALB-3 has the strongest activity of antioxidant.Through scientific research,this experiment proved that the efficacy materail base of F.aurantii are not just the volatile oils,alkaloids and flavonoids that people have always thought,also includes polysaccharides.The research of antioxidant activity of polysaccharides further deepens the understanding of F.aurantii efficacy,and provides a scientific basis for the further research and development and use on F.aurantii polysaccharides.(2)Study on mechanism of CALB-3 induction cytokines of PBMCs based on MAPKs signaling pathwaysIn the TCM clinical,F.aurantii often used as the spleen and stomach medicine,bu so far,the spleen efficacy material base is still not clear.Based on the study of nature and flavor of F.aurantii,found F.aurantii polysaccharides has the promoting the effect of mouse spleen cell proliferation,therefore,To further elucidate the role of CALB-3 as a biological response modifier,the mechanism of the immunomodulatory activity of CALB-3 in human peripheral blood mononuclear cells(PBMCs)was investigated in this study.We demonstrated that stimulation of PBMCs with CALB-3 resulted in an increase in cell proliferation and production of nitric oxide(NO)and cytokines.The mechanism for this increase was rapid CALB3-mediated phosphorylation of several mitogen-activated protein kinases(MAPKs):extracellular signal-regulated kinase(ERK),c-Jun N-terminal kinase(JNK)and p38.Using pharmacologically characterized MAPKs inhibitors,western blot analyses,we extensively examined and dissected the role of individual MAPKs in the regulation of pro-IL-1/IL-1.We found that CALB3 enhances the nuclear translocation of p65 by increasing the phosphorylation.Overall,this study clarified the immunostimulating properties of CALB3 in PBMCs,highlighting the role of the F.aurantii polysaccharides CALB3 as an efficacious biological response modifier in oncologic immunotherapy.(3)The study on anti-radiation effect of CALBThe study found that there are both good anti-oxidant activity and immunoregulation of the F.aurantii polysaccharides.Combined biological activity of CALB one of F.aurantii polysaccharides explore the effect of anti-radiation in mice.By detecting survival rate of mice,each dose group could significantly increase the survival rate of radiation in mice.CALB(high and middle group)can increase of bone marrow cell DNA content and decrease of bone marrow cells micronucleus.Moerover induces spleen cell proliferation.CALB group(high dosage group)can reduce the MDA content,and activity of SOD,GSH-PX was notability increased.Through this chapter,the experimental results show that a number of physiological indexes of mice had an obvious damage effect by radiation,and each dose group of CALB with different degree of protection against radiation injury.Overall,three groups of CALB have respective advantages in terms of anti-radiation effect5 Tangeretin exerts anti-neuroinflammatory effects via NF-?B modulation in lipopolysaccharide-stimulated microglial cellsIncreasing evidence suggests that tangeretin,a flavonoid from citrus fruit peels,exhibits anti-inflammatory properties and neuroprotective effects in animal disease models.However,the underlying molecular mechanisms are not clearly understood.In this study,we investigated whether tangeretin suppresses excessive microglial activation implicated in the resulting neurotoxicity following stimulation with lipopolysaccharide(LPS)in primary rat microglia and BV-2 microglial cell culture models.The results showed that tangeretin decreased the production of nitric oxide(NO),prostaglandin E2(PGE2),tumor necrosis factor alpha(TNF-a),interleukin-1 beta(IL-1?),and interleukin-6(IL-6),in a dose-dependent manner.Additionally,it inhibited the LPS-induced expression of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)(examined at the protein level)as well as TNF-a,IL-1?,and IL-6(examined at the mRNA level)in microglial cells.To explore the possible mechanisms underlying these inhibitions by tangeretin,we examined the mitogen-activated protein kinase(MAPK)protein levels and the NF-?B protein signaling pathway.Tangeretin clearly inhibited LPS-induced phosphorylation of ERK,N-terminal Kinase(JNK),and p38.In addition,tangeretin markedly reduced LPS-stimulated phosphorylation of I?B-a and IKK-?,as well as the nuclear translocation of the p65 subunit of pro-inflammatory transcription factor NF-?B.Taken together,these results support further exploration of the therapeutic potential and molecular mechanism of tangeretin in relation to neuroinflammation and neurodegenerative diseases accompanied by microglial activation. |
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