Anti-inflammatory Constituens From Three Plants Of Genus Illicium And Their Chemotaxonomic Significance

【Background and Objective】Traditional Chinese Medicine (TCM) played a significant role in the5000-yearhistory of China. The development of TCM is facing a big challenge from rapidlydeveloping modern medicine. What are the active compounds of TCM? How to control thequality of a crude extract with so many complex constituents? The sources of some TCMare less and less. The unclearness of the active compounds and mechanisms of TCM,together with the uncontrollability of its quality and the decrease of the sources of TCMare problems that need to be overcome by researchers.Illicium difengpi K.I.B. et K.I.M is a shrub native to China. Its stem bark was listed inChinese Pharmacopeia as a treatment of rheumatoid arthritis (RA). It was reported that49compounds were isolated from the extract of the stem bark of I.difengpi, includingphenylpropanoids, lignans, terpenoids, phenyl acids, flavones, steroids and others. Over60compounds were determined by the GC/MS methods from the essential oil. There werefew reports on the chemical constituents and the pharmacology mechanisms of I.difengpi;the quality control method needs to be improved. In order to provide chemistry support forpharmacological study and quality control of I.difengpi, our study led to systematicalisolation and structural determination of pure compounds. The anti-inflammatory activityof isolated compounds was also evaluated.I.difengpi is distributed in20cities in Guangxi and Yunnan province in China. Itgrows in the forests over1800meters. The availability of the bark of I.difengpi is limitedbecause of its specific growing environment, and disorderly excavation. It is almostdepleted to meet market demands and has already been listed as one of the endangeredplants in China. On the basement of chemical study, anti-inflammatory activity screen andan improved quality control method, which would reflect the major chemical constituentsand active compounds, to search for a candidate substitute is of great importance. We alsodo systematical isolation and activity screen of other two plants from the same genus,I.tsaii A.C.Smith and I.burmanicum Wils., to compare the chemical constituents and anti-inflammatory activity of these plants, discuss the systematic position and phylogeneticrelationship of the genus Illicium and evaluate their potential to be used as a substitute ofI.difengpi. 【Methods and Results】129compounds were isolated from the ethanol extract of these three plants of genusIlliciaceae using chromatography methods including column chematography, thin layerchematography and preparative HPLC. Their structures were determined by analyzing MS,spectroscopic and NMR data. Two new triterpenoids, a new amide compound and a newphenolic compound were isolated from I.difengpi, along with sesquiterpenoids, lignans andother phenolic compounds as main constituents. Most of the pure compounds from thisplant were simple structures and their biosynthesis may shorter than complex structures,confirming that the Illiciaceae was one of the ANITA basal angiosperms. This is inaccordance with reported papers. The presence of two new secocycloartane triterpenoids,which were widely isolated from genus Kadsura, showed the close relation between thesetwo genus.28known compounds were isolated from I.tsaii. What we have to mention wasthat the skeletal structure of the sesquilignans isolated from this plant contained three C6-C3moieties, one phenyl ring of which was saturated. This type of structure was distinct inthe sect. Illicium. This structure may show clue with the group division of Illiciaceae plants.9new prenylated C6-C3compounds and4new dimeric prenylated C6-C3compounds wereisolated from I.burmanicum. The great chemical constituent difference betweenI.burmanicum and the other two plants showed that I.difengpi and I.tsaii may have closerrelation.Natural products regulate the process of inflammation through mediating multipletargets. In our research, the isolated compounds were evaluated towards multiple targetsrelated to inflammatory, including TNF-, NF-κB, iNOS and NAG-1. We also did theantioxidant activity screen of the isolated compounds. We found that lignans andphenylpropanoids showed anti-inflammatory towards multiple targets, especiallycompounds macranthol and isodunnianol showed great potency.【Conclusion】The isolation and anti-inflammatory screen of129compounds from three plants ofgenus Illicium play a great role in the evaluation of the active constituents, improvement ofquality control method and appraising the substitute of I.difengpi. I.tsaii showed closerrelation with I.difengpi than I.burmanicum. The study of two different plants of Illicium isan effective try of the appraising the substitute of I.difengpi and can be used as referencefor further study.