Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in...Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in vitro,but reasonable explanations for the differential hepatotoxicity have not been provided.Herein,the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs(diosbulbins A,B,C,F).In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3 A4 at the atomic level were simulated by molecular docking.Results showed that DLs exhibited varied cytotoxicities,and that CYP3 A4 played a modulatory role in this process.Moreover,structural variation may cause different affinities between DLs and CYP3 A4,which was positively correlated with the observation of cytotoxicity.In addition,analysis of the glutathione(GSH)conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs,whereas,GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity.Collectively,our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.展开更多
本研究通过简化基因组测序(2b-RAD)技术,对浙江省三门湾海域定居性优势无脊椎动物(哈氏仿对虾、口虾蛄、脊尾白虾、三疣梭子蟹、曼氏无针乌贼、棒锥螺和牡蛎)进行遗传结构和遗传多样性分析,以评估三门湾海域水生无脊椎动物资源现状,并...本研究通过简化基因组测序(2b-RAD)技术,对浙江省三门湾海域定居性优势无脊椎动物(哈氏仿对虾、口虾蛄、脊尾白虾、三疣梭子蟹、曼氏无针乌贼、棒锥螺和牡蛎)进行遗传结构和遗传多样性分析,以评估三门湾海域水生无脊椎动物资源现状,并为渔业可持续发展提供物种遗传资源监测依据。7个物种共获得12336~108139个SNP位点,变异位点比例为0.168%~1.571%。遗传分析结果显示,7个物种的平均核苷酸多样性(Pi)为0.147~0.306,平均观测杂合度(Ho)为0.142~0.289,多态信息含量(Polymorphism Information Content,PIC)为0.124~0.234,个体间平均遗传距离为0.118~0.246。本研究表明,三门湾水域7种代表性无脊椎动物中,生物群体变异位点比例较低,遗传多样性水平较低,且相同种群个体间的遗传分化较小,结合本次对三门湾海域渔业资源调查分析,这可能与人工增殖放流等因素有关。展开更多
基金supported by the National Natural Science Foundation of China(No.81773993)
文摘Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in vitro,but reasonable explanations for the differential hepatotoxicity have not been provided.Herein,the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs(diosbulbins A,B,C,F).In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3 A4 at the atomic level were simulated by molecular docking.Results showed that DLs exhibited varied cytotoxicities,and that CYP3 A4 played a modulatory role in this process.Moreover,structural variation may cause different affinities between DLs and CYP3 A4,which was positively correlated with the observation of cytotoxicity.In addition,analysis of the glutathione(GSH)conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs,whereas,GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity.Collectively,our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.
文摘本研究通过简化基因组测序(2b-RAD)技术,对浙江省三门湾海域定居性优势无脊椎动物(哈氏仿对虾、口虾蛄、脊尾白虾、三疣梭子蟹、曼氏无针乌贼、棒锥螺和牡蛎)进行遗传结构和遗传多样性分析,以评估三门湾海域水生无脊椎动物资源现状,并为渔业可持续发展提供物种遗传资源监测依据。7个物种共获得12336~108139个SNP位点,变异位点比例为0.168%~1.571%。遗传分析结果显示,7个物种的平均核苷酸多样性(Pi)为0.147~0.306,平均观测杂合度(Ho)为0.142~0.289,多态信息含量(Polymorphism Information Content,PIC)为0.124~0.234,个体间平均遗传距离为0.118~0.246。本研究表明,三门湾水域7种代表性无脊椎动物中,生物群体变异位点比例较低,遗传多样性水平较低,且相同种群个体间的遗传分化较小,结合本次对三门湾海域渔业资源调查分析,这可能与人工增殖放流等因素有关。
