Studies On Preparation And Anti-obesity Activity Of Prenylated Flavonoid Extract In Psoralea Corylifolia Linn

The seeds of Psoralea corylifolia L.,a traditional Chinese medicine,has been used for many years to treat leukoderma and osteoporosis.However,the safety of meroterpenes and coumarins has been concerned,because they can induce cholestatic hepatotoxicity and nephrotoxicity.Several pharmacological studies have been examined the flavonoids from the seeds of P.corylifolia and reported numerous biological activities.In our previous work,bavachinin(BVC),as a pan-PPAR agonist,has contributed on regulation of lipid metabolism and glucose homeostasis.Many flavonoids of Psoralea corylifolia L.also showed potent agonist activity of PPAR-α/γ,which suggested that it might had synergistic effects to co-regulate lipid and glucose metabolism.Object:The present work is to enrich prenylated flavonoid-standardized extract(PFE)from the seeds of P.corylifolia.,and investigated the mechanism of anti-obesity and browning in s WAT in DIO mice.Method:The prenylated flavonoid-standardized extract were prepared by silica gel column and polyamide column chromatography.HPLC chromatography was applied to identify the main peaks chromatogram of PFE,which showed that PFE contained free monoterpene(bakuchiol)and coumarins(psoralen and isopsoralen).The contents of seven major flavonoid in PFE,including bavachin,neobavaisoflavone,isobavachalcone,bavachinin,psoralidin,corylifol A,and bavachalcone,were quantified by HPLC analysis.C57BL/6 mice were fed a controlled high-fat diet(HFD)or HFDs with PFE 0.2% or 0.5%(w/w)for 12 weeks.In vitro,the differentiation of 3T3-L1 and C3H10T1/2 cells were used to elicit thermogenesis in the presence of PFE.Results:Both the enrichment methods of silica gel column and the polyamide column chromatography could effectively remove the psoralen coumarin components(psoralen and isopsoralen)and bakuchiol and retain the active ingredients of flavonoids in Psoralea corylifolia L.The flavonoids contents of PFE prepared by silica gel column and the polyamide column were 50.1% and 48.7%,respectively.In vivo,PFE obviously reduced body weight and fat mass in a dose-dependent manner,and increased energy expenditure,including oxygen consumption and carbon dioxide production.PFE might improve glucose homeostasis by increasing glucose transport and insulin signaling in adipose tissue.Meanwhile,PFE prevented hepatic steatosis by increasing lipid oxidation and secretion in HFD-fed mice.Moreover,PFE induced browning in s WAT,increased BAT activity and the differentiation of 3T3-L1 by increasing the expression of uncoupling protein 1(UCP1)and other thermogenic genes.Conclusion:The enrichment methods of silica gel column and the polyamide column chromatography could effectively prepare the prenylated flavonoid-standardized extract(PFE)from the seeds of Psoralea corylifolia L.We investigated the effects of PFE on countering obesity and regulation of lipid metabolism and glucose homeostasis.PFE increases energy expenditure and stimulates thermogenesis in subcutaneous white adipose tissue(s WAT)and brown adipose tissue(BAT),which might relate to activate the phosphorylation of AMPK and P38.