OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resv...OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resveratrol(trans-3,5,4-trihydroxystilbene),pterostilbene(trans-3,5-dimethoxy-4-hydroxystilbene),resveratrol trimethyl ether(trans-3,5,4-trimethoxystilbene)and some other herbal resveratrol analogs were extracted from the authors′recent publications and compared.RESULTS Aqueous solubility,to different extent,has been identified as a barrier to oral absorption of resveratrol and its analogs.In addition,the para hydroxyl group(s)on the aromatic ring was less liable to metabolism compared to the meta-hydroxyl group(s).Pterostilbene and resveratrol trimethyl ether displayed more superior pharmacokinetic properties than resveratrol,i.e.much slower clearance and abundant plasma exposure.CONCLUSION Pterostilbene appears to be a favorable candidate for further development.Resveratrol analogs with meta-hydroxyl group(s)might have poor metabolic stability and suffer from rapid clearance and low oral bioavailability.展开更多
基金The project supported by a start-up grant from the National University of Singapore(R148000174133)
文摘OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resveratrol(trans-3,5,4-trihydroxystilbene),pterostilbene(trans-3,5-dimethoxy-4-hydroxystilbene),resveratrol trimethyl ether(trans-3,5,4-trimethoxystilbene)and some other herbal resveratrol analogs were extracted from the authors′recent publications and compared.RESULTS Aqueous solubility,to different extent,has been identified as a barrier to oral absorption of resveratrol and its analogs.In addition,the para hydroxyl group(s)on the aromatic ring was less liable to metabolism compared to the meta-hydroxyl group(s).Pterostilbene and resveratrol trimethyl ether displayed more superior pharmacokinetic properties than resveratrol,i.e.much slower clearance and abundant plasma exposure.CONCLUSION Pterostilbene appears to be a favorable candidate for further development.Resveratrol analogs with meta-hydroxyl group(s)might have poor metabolic stability and suffer from rapid clearance and low oral bioavailability.
