Study On Mechanism Of Anti-inflammatory Activity And Bioactive Components Of Propolis

Propolis is a resinous substance collected by Apis mellifera L.from various tree buds,which use as a sealant in the hive.Propolis has been testified a wide range of pharmacological activities,such as anti-tumor,antiviral,anti-inflammatory,anti-oxidant and so on.Currently,propolis has been widely used in foods and health products to prevent diseases and promote health.Propolis has been displayed significant anti-inflammatory effects,but its functional compounds and mechanisms were not fully understood.In the past,we isolated,purified and identified 11 compounds from Chinese propolis water extracts,and separated 8 subfractions in the propolis ethyl acetate extracts.In this study,we established two inflammatory models that using oxidized low-density lipoprotein(ox-LDL)and lipopolysaccharide(LPS)induce human umbilical vascular endothelial cell(HUVEC)injury.The anti-inflammatory activities of 11 compounds(caffeic acid phenethyl ester,ferulic acid,pinocembrin,isoferulic acid,pinobanksin,galangin,caffeic acid,caffeic acid benzyl ester,apigenin,chrysin and 3,4-dimethoxy cinnamic acid)and 8 subfractions have been evaluated by two models.The results showed that these compounds or subfractions could improve cell viability and protect endothelial cells.We deduced that the bioactive components of propolis on the protection effects of HUVEC were not determined by a single component,but a synergic effect of phenolic acids and flavonoids.After clarifying the propolis efficient components,we studied the anti-inflammatory and protective mechanisms of propolis by two inflammatory models.The main findings are as follows:(1)Chinese propolis ethyl acetate extracts(EACP)and Brazilian green propolis ethanol extracts(EEBP)could activate PI3K/Akt/mTOR signaling pathway as well reduce reactive oxygen species(ROS)production and protect mitochondrial membrane potential(MMP)to inhibit apoptosis and autophagy in ox-LDL-induced HUVEC.Further studies on EEBP found that propolis' s antioxidant stress was mainly through activation of PI3K/Akt/mTOR signaling pathway to elevate Nrf2 and its downstream signaling molecule HO-1.(2)Chinese propolis ethanol extract(EECP)inhibited MAPK and TLR4-NF?B signaling pathway to exert anti-inflammatory effects in LPS-induced HUVEC.Further studies had found that EECP also inhibited p53 nuclear translocation inhibiting LPS-induced autophagy in HUVEC.In summary,the present shows that the anti-inflammatory efficient compounds of propolis are not determined by a single component,while multiple signaling pathways are involved in the anti-inflammatory mechanism of propolis.