基于酶抑制、转运体和纳米粒探究醋乳香多糖促进乳香酸类成分体内吸收的作用机制OA

This study aimed to investigate the promoting effects of polysaccharides from frankincense and vinegar-processed frankincense on the absorption of 3-O-acetyl-11-keto-β-boswellic acid(AKBA)and 11-keto-β-boswellic acid(KBA),and to explore their potential mechanisms through inhibition of carboxylesterase 2(CES2)and organic anion-transporting polypeptides(OATPs),as well as the formation of nanoparticles(NPs).The effects of polysaccharides from frankincense and vinegar-processed frankincense on the pharmacokinetic parameters of AKBA and KBA were analyzed by LC-MS/MS.The inhibitory effects of polysaccharides on CES2 were studied through in vitro human liver microsome metabolic experiments.The uptake of AKBA and KBA was analyzed via cells transfected with OATP1B1,OATP1B2,and the inhibitory effects of polysaccharides on expression of OATP1B1,OATP2B1 at the mRNA level were compared.Self-assembled polysaccharide-AKBA,KBA NPs were prepared and their physicochemical properties and in vitro release behaviors were characterized.The results showed that the polysaccharides,especially those from vinegar-processed frankincense,significantly enhanced the oral bioavailability of AKBA and KBA.Polysaccharides non-competitively inhibited CES2,thereby blocking the metabolism of AKBA.Moreover,they down-regulated the mRNA levels of OATP1B1,OATP2B1,reducing the cellular uptake of AKBA and KBA.Additionally,the 4 polysaccharides protected active ingredients from metabolism by forming NPs with AKBA and KBA.Overall,this study proved that vinegar-processed frankincense polysaccharides had the strongest promoting effects on the absorption of AKBA and KBA,and illustrated the roles of polysaccharides in the inhibition of CES2 and OATPs and formation of NPs for the first time.The findings offer a valuable clue for illustrating the principle underpinning the effect enhancement through vinegar processing from the view of polysaccharides.