The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral admin...The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract,respectively,plasma samples were obtained at various times and the concentrations of GA,liquiritigenin,and isoliquiritigenin were measured by LC-MS.The effects of Laminaria extract on pharmacokinetics of GA were also investigated,following single-dose and multidose of glycyrrhizic acid(GL).The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model.The metabolism of GL to GA in the contents of small and large intestines was also studied.The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA,accompanied by a shorter Tmax.Similar alteration was observed following multidose administration.However,pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria.Similarly,Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed.The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum,but did not affect the intestinal absorption of GA.It was found that Laminaria enhanced the metabolism of GL to GA in large intestine.In conclusion,Laminaria increased plasma exposures of GA following oral administration of liquorice or GL,which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.展开更多
Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.L...Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.Lyzl deficiency led to vascular inflammatory aging,including damage to indicators related to oxidative stress,vascular function,and inflammation in the serum and vascular tissues of wild-type(WT)and Lyz1^(-/-)mice.The 16S ribosomal RNA sequencing of intestinal contents revealed increased Bifidobacterium and its metabolism of acetate,butyrate,omega-muricholic acid,propionate,and valeric acid in Lyz1^(-/-)mice compared with that in WT mice.Additionally,RNA sequencing of vascular tissues identified differentially expressed genes in Lyz1^(-/-)mice compared with those in WT mice,as well as enrichment of the common phosphatidylinositol 3-kinase(Pl3K)-Akt signaling pathway.Vascular inflammatory aging phenotypes were detected in the blood vessels of antibiotic-treated and germ-free mice,and the PI3K-Akt signaling pathway was inhibited.Importantly,intravenous LYZ administration worsened the pathological conditions,whereas oral LYZ administration successfully restored the gut microbial balance and reversed the vascular inflammatory aging phenotypes.Collectively,this study establishes LYZ as a novel biomarker for age-related vascular diseases and the gut microbiota-PI3K-Akt axis as a promising therapeutic target.展开更多
基金supported by funding from the National Basic Research Program of China(973 Program)(Nos.2011CB505300,2011CB505303)
文摘The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract,respectively,plasma samples were obtained at various times and the concentrations of GA,liquiritigenin,and isoliquiritigenin were measured by LC-MS.The effects of Laminaria extract on pharmacokinetics of GA were also investigated,following single-dose and multidose of glycyrrhizic acid(GL).The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model.The metabolism of GL to GA in the contents of small and large intestines was also studied.The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA,accompanied by a shorter Tmax.Similar alteration was observed following multidose administration.However,pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria.Similarly,Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed.The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum,but did not affect the intestinal absorption of GA.It was found that Laminaria enhanced the metabolism of GL to GA in large intestine.In conclusion,Laminaria increased plasma exposures of GA following oral administration of liquorice or GL,which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.
基金supported by the National Natural Sciences Foundation of China(82305072,82305064,and 82300345)the Natural Science Foundation of Jiangsu Province(BK20230184)+6 种基金the Science and Technology Development project of Jiangsu Provincial Administration of Traditional Chinese Medicine(YB2020043)the Wuxi Municipal Health Commission Scientific Research Fund Youth Project(Q202106 and Q202225)The Taihu Lake Talent Project of Wuxi Science and Technology Bureau(K20221027)the Medical Key Discipline Program of Wuxi Health Commission(HB2023044 and HB2023051)the Chongqing Natural Science Foundation(CSTB2024NSCQMSX0368)the high-level hospital clinical research fees of Fu Wai Hospital,CAMS(grant 2023-GSP-QN-23)the Doctoral Talent Startup Fund of Affiliated Hospital of Jiangnan University.
文摘Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.Lyzl deficiency led to vascular inflammatory aging,including damage to indicators related to oxidative stress,vascular function,and inflammation in the serum and vascular tissues of wild-type(WT)and Lyz1^(-/-)mice.The 16S ribosomal RNA sequencing of intestinal contents revealed increased Bifidobacterium and its metabolism of acetate,butyrate,omega-muricholic acid,propionate,and valeric acid in Lyz1^(-/-)mice compared with that in WT mice.Additionally,RNA sequencing of vascular tissues identified differentially expressed genes in Lyz1^(-/-)mice compared with those in WT mice,as well as enrichment of the common phosphatidylinositol 3-kinase(Pl3K)-Akt signaling pathway.Vascular inflammatory aging phenotypes were detected in the blood vessels of antibiotic-treated and germ-free mice,and the PI3K-Akt signaling pathway was inhibited.Importantly,intravenous LYZ administration worsened the pathological conditions,whereas oral LYZ administration successfully restored the gut microbial balance and reversed the vascular inflammatory aging phenotypes.Collectively,this study establishes LYZ as a novel biomarker for age-related vascular diseases and the gut microbiota-PI3K-Akt axis as a promising therapeutic target.
