Study On Chemical Constituents Of Species Dysoxylum And Its PTP1B Inhibitory

Objective: Diabetes,as one of the most serious health threats,may lead to a variety of serious complications.Although there are a variety of hypoglycemic agents in clinical practice,various adverse reactions have limited their wide application.Type 2 diabetes is a major type of diabetes caused by impaired insulin secretion and insulin resistance.Protein tyrosine phosphatase 1B(PTP1B)is a negative regulator of insulin signal transduction and has been widely recognized as an attractive target for the treatment of type 2 diabetes.Therefore,the development of PTP1 B natural inhibitors has become an effective way to reduce blood sugar.A series of bioactive compounds with various structural types have been found in the genus Dysoxylum,such as triterpenoids,alkaloids,sterols,diterpenes and flavonoids.The previous research of the research group found that a variety of components in Dysoxylum plants have inhibitory effects on PTP1 B.Based on this,this paper studied the chemical components of three less studied Dysoxylum plants,including Dysoxylum cupuliforme,Dysoxylum densiflorum and Dysoxylum laxiracemosum,in order to provide scientific basis for the discovery of active components inhibiting PTP1 B.Methods: Silica gel column chromatography,MCI column chromatography,Sephadex LH-20,HPLC,preparation of RPLC and other modern separation methods,as well as MS,1H NMR,13 C NMR,HSQC,1H-1H COSY,HMBC and other analysis methods were used to separate,purify and identify the chemical components of Dysoxylum cupuliforme,Dysoxylum densiflorum and Dysoxylum laxiracemosum,then to reaserch the PTP1 B inhibitory activity.Results & Conclusion: 1.A total of 65 compounds were isolated and identified from three Dysoxylum species,64 of which were not repeated,including 4 new compounds,all of which are diterpenes;Seventeen compounds in the Dysoxylum densiflorum were isolated for the first time;All compounds in the two species of Dysoxylum cupuliforme and Dysoxylum laxiracemosum were isolated for the first time.A total of 15 compounds were isolated and identified from Dysoxylum cupuliforme,including 1 diterpene,3 triterpenoids,10 sesquiterpenoids,1 other type.A total of 28 compounds were isolated and identified from Dysoxylum densiflorum,all of which were diterpenes,and 4 new compounds(compounds 19*,28*,31*,39*).A total of 21 compounds were isolated and identified from Dysoxylum laxiracemosum,including6 triterpenoids,1 flavonoid,10 sesquiterpenoids and 5 other types.2.Compounds 2,17,21,32,35,37,42,44,47,54,58,61 and 62 had significant inhibitory activity against PTP1 B,and the inhibition rate was significantly higher than that of suramin sodium,with IC50 ranging from 0.0514 to 84.12 μg/m L.The relationship between the results and structure-activity was simply analyzed.In addition,this paper reviews the research progress of diterpenoids in Meliaceae,and finds that Meliaceae has good research prospects and development and utilization value.