简介：Pomegranateleaf(PGL)hasadefiniteroleinregulatinglipidmetabolism.However,pharmacokineticresultsshowthemainactiveingredient,ellagicacid,inPGLhasloweroralbioavailability,suggestingthatthelipid-loweringeffectofPGLmayactthroughinhibitinglipidabsorptioninthesmallintestine.Ourresultsdemonstratedthatpomegranateleafanditsmainactiveingredients(i.e.,ellagicacid,gallicacid,pyrogallicacidandtannicacid)werecapableofinhibitingpancreaticlipaseactivityinvitro.Incomputationalmoleculardocking,thefouringredientshadgoodaffinityforpancreaticlipase.AcutelipidoverloadexperimentsshowedthatalargedosageofPGLsignificantlyreducedserumtotalcholesterol(TG)andtriglycerides(TC)levelsinadditiontoinhibitingintestinallipaseactivity,whichdemonstratedthatPGLcouldinhibitlipaseactivityandreducetheabsorptionoflipids.WealsofoundthatPGLcouldreversethereducedtight-junctionproteinexpressionduetointestinallipidoverload,promoteOccludinandClaudin4expressioninthesmallintestine,andenhancetheintestinalmucosalbarrier.Inconclusion,wedemonstratedthatPGLcaninhibitlipidabsorptionandreducebloodTGandTCbytargetingpancreaticlipase,promotingtight-junctionproteinexpressionandtherebypreventingintestinalmucosadamagefromanoverloadoflipidsintheintestine.