Based On Chemical Classification, The Material Basis Of Tangerine Plants And The Different Anti-inflammatory Effects Of Taro And Clam Shells Were Discussed

Citrus fruits,which are the most popular TCMs of homology of medicine and food,are of great interest because they contain large amounts of dietary phenoloids possessing important therapeutic properties for human health,and Citrus fruits and their juices are consumed in large quantities around the world.Four different Citrus TCMs recorded in Chinese Pharmacopeia,2015 edition,Zhishi(ZS,young fruit of C.aurantium L.),Zhiqiao(ZQ,immature fruit of C.aurantium L.),Qingpi(QP,pericarps of the young or immature fruit of C.reticulate Blanco)and Chenpi(CP,pericarps of the ripe fruit of C.reticulate Blanco),were used as research subjects.Although they belong to the same genus,their efficacy and clinical indications are different.As we know,Citrus fruits contain a large number of bioactive phenolic metabolites,which have been associated with lower risks of different types of cancer and cardiovascular diseases and have been shown to exhibit antioxidant,anti-inflammatory and anti-ageing activities.According to our previous research,the total phenolic products could be used as characteristic markers for species discrimination of different Zhishi samples,while phenolic metabolites varied over the ripening process.Zhishi and Zhiqiao,the dried young fruit and unripe fruits of Citrus aurantium L.,which are the most famous TCMs in China and commonly used in worldwide that contain a large number of bioactive phenolic metabolites associated with human health.They have been used as drugs for regulating balance and strengthening homeostasis of human body in Chinese clinical applications and now are recorded in Chinese Pharmacopeia 2015 edition.In recent years,more and more investigations have focused on the anti-inflammatory functions of diversified phenolic metabolites contained in Zhishi and Zhiqiao,such as suppressing inflammatory cytokines,modulating inflammation-related pathways and regulating the disorders of metabolism.Zhishi and Zhiqiao represent the complexity and diversity of multi-components in TCMs.In our previous studies,a novel method has been established to illustrate the different quality control markers of phenolic components in Zhishi and Zhiqiao by plant metabolomics and quantitative plasma pharmacochemistry analysis.Therefore,taking account of their respective characteristic and variant components in a massive and complicated mixture is more scientific and logical to uncover the mechanisms of interaction in multi-target,multi-function and multi-pathway modes.The First Chapter:Chemotaxonomic classification applied to the authentication of closely related Citrus TCMs using UPLC-Q-TOF-MS-based metabolomicsThis manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely related Citrus fruits in Traditional Chinese Medicines(TCMs).UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages.Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling,creating a bridge between genotype and phenotype.To further investigate the different metabolites in four closely related Citrus TCMs,non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites.The results presented in this manuscript indicate that primary metabolites enable the discrimination of species,whereas secondary metabolites are associated with species and the ripening process.In addition,analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages.Ultimately,this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses.The Second Chapter:Anti-inflammatory effect of Zhishi and Zhiqiao revealed by network pharmacology integrated with molecular mechanism and metabolomics studiesInflammatory response due to its complex pathogenesis is a critical contributor for the development and complications of many diseases.Zhishi and Zhiqiao as the famous Citrus herbal medicine are rich in bioactive phenolic constituents with multiple anti-inflammatory activities.Herein,a multi-components-target-pathway network was constructed to elucidate the variant anti-inflammatory efficient of Zhishi and Zhiqiao by integrating multi-constituents determination,network pharmacology,molecular mechanism on cells and metabolomics in integral animals.The different anti-inflammation effect of Zhishi and Zhiqiao against LPS-induced inflammatory responds in RAW 264.7 cells and rats was experimentally verified.It indicated that Zhishi mainly suppressed the MAPK signaling pathway,whereas Zhiqiao emphasized on PPAR-AKT signaling pathways,simultaneously,to block the inflammatory process.Meanwhile,Zhishi and Zhiqiao both exhibited an anti-inflammation effect by inhibiting the NF-?B signaling pathway to reduce the production of inflammatory mediators.For the metabolomics study,Zhishi and Zhiqiao exhibited variant corrections of the disordered metabolic pathways through amino acid metabolism,glycometabolism and lipid metabolism.These findings can assist in developing the usage of Zhishi and Zhiqiao on inflammatory.