Study On Chemical Constituents Of Tussilago Farfara And Aglaia Lawii And Their Antidiabetic Activity

Diabetes has always been a highly concerned and prevalent metabolic disease,with complex pathogenesis,closely related to inflammation,oxidative stress,etc.The age of onest is becoming younger and younger.At present,although there are a large number of therapeutic drugs available in clinic practice that are effective in lowering blood glucose,they still do not curb the occurrence and development of diabetes,and some of them also showed drug resistance and side effects during long-term use.It is increasingly important to find new anti-diabetic drugs.Compared with chemical drugs,natural products have excellent characteristics such as extensive multi-target pharmacological activity and better human body adaptability.They have always been an important source for innovative drug development and pharmacological mechanism exploration.In this thesis,two plants,Tussilago farfara and Aglaia lawii,were studied.A variety of compounds were isolated from the two medicinal plants that rich in terpenoids by using various separation methods and structure elucidation methods.Their bioactivities were evaluated by using diabetes and inflammatory cell models,with the aim of discovering active molecules regulating diabetes.The air-dried flower of Tussilago farfara and whole plant of Aglaia lawii were ground and extracted with 95%ethanol.The extracts were separated by macroporous resin,MCI resin,silica gel,C₁₈ reverse silica gel,and sephadex LH-20 gel column chromatography,as well as semi-preparative high performance liquid chromatography and other separation methods.Structures of the isolates were identified by nuclear magnetic resonance,high resolution mass spectrometry,infrared spectroscopy,ultraviolet spectroscopy,electronic circular dichroism and other modern spectroscopic techniques.A total of 52 compounds were isolated and identified from the two plants,including a new seco-ring skeleton sesquiterpenoid（1）,two new bisabolane-type sesquiterpenoids（2 and 3）,and a new oplopane-type sesquiterpenoid（4）.The32 known compounds are 10 bisabolane-type sesquiterpenoids（5-14）and 10 oplopane-type sesquiterpenoids（15-23）,a triterpenoid（24）,two steroids（25-26）,five phenolic acids（27-31）,two flavonoids（32-33）,and two long chain fatty acids（34-35）.Sixteen known compounds were isolated from Aglaia lawii,and five sesquiterpenoids（1-5）were isolated for the first time from this plant.The anti-diabetic and anti-inflammatory activities of some of the isolated compounds were evaluated by using C2C12 myotube cell glucose uptake model and LPS-induced RAW264.7macrophage cell inflammation model.The results showed that compound 2 from Tussilago farfara and compound 5 from Aglaia lawii could significantly promote glucose absorption at40μM.The new compounds 1,2,4 and the known compound 16 from Tussilago farfara inhibited LPS-induced NO production in a dose-dependent manner,and compounds 4 and 16had stronger activity than that of the positive drug dexamethasone at the same dose.Further studies by Western Blotting showed that they can reduce the expression of iNOS and NF-КB p65 and inhibit the phosphorylation of p65.It is particularly important to find that the new compound 2 has the dual effects of promoting glucose uptake and inhibiting NO production.Further research on this compound may led to the discovery of new chemical entities with multi-target effects.In summary,several series of new and known sesquiterpenoids were found by studying the chemical constituents of Tussilago farfara and Aglaia lawii.Through the anti-diabetic and anti-inflammatory cell model activity evaluation experiments,several active compounds that may regulate diabetes and inflammation were found,which has certain reference value for the development of new anti-diabetic drugs.