Acute kidney injury(AKI)is a critical clinical condition characterized by rapid renal function decline,with high morbidity,mortality,and healthcare costs.Traditional Chinese medicine(TCM)has shown potential effects on...Acute kidney injury(AKI)is a critical clinical condition characterized by rapid renal function decline,with high morbidity,mortality,and healthcare costs.Traditional Chinese medicine(TCM)has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models.Scutellaria barbata D.Don(SB)and Scleromitrion diffusum(Willd.)R.J.Wang(SD),a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities.Using advanced chromatographic separation technology,we enriched the effective fractions of water extracts from SB-SD,obtaining selfassembled herbal nanoparticles(SB and SD nanoparticles,SSNPs)rich in flavonoids and terpenoids.These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Oral administration of SSNPs in mice resulted in absorption into the bloodstream,formation of a protein corona,reduced macrophage phagocytosis,and enhanced bioavailability and renal targeting.Furthermore,we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids.Kinetic studies and in situ transmission electron microscopy(in situ TEM)revealed that these compounds selfassemble via supramolecular forces like hydrogen bonding andπ-πinteractions,forming stable nanostructures.This study elucidates the renoprotective effects and mechanisms of SB and SD,and provides a novel approach for the development of TCM-based nanomedicines,highlighting the potential of nanoTCM in AKI treatment.展开更多
目前新药研发高投入高失败率的“反摩尔定律(Eroom′s Law)”提示,现有药物研发将复杂人体系统简化为可研究模型(还原论方法)到最终回归复杂人体系统验证效果(系统论方法)存在转化研究上的巨大鸿沟。近年来全球创新药研发策略发生了两...目前新药研发高投入高失败率的“反摩尔定律(Eroom′s Law)”提示,现有药物研发将复杂人体系统简化为可研究模型(还原论方法)到最终回归复杂人体系统验证效果(系统论方法)存在转化研究上的巨大鸿沟。近年来全球创新药研发策略发生了两个重大变化:一是希望将表型药物发现(phenotypic drug discovery,PDD)和靶点药物发现(target-based drug discovery,TDD)结合起来以加速创新药研发,二是更加关注多靶点药物设计(multi-target drug design,MTDD)及其对疾病动态网络系统调节的重要性。研究发现,中医方剂及其组成药物衍生的方剂纳米体(formula-derived nanoparticles of TCM,FDN),包括中药外泌体(TCM-Exo)、中药汤剂体(TCM-Deco)、中药碳量子点(TCM-CDs)、中药成分本草体(TCM-Benc)等自组装纳米聚集体,可作为中药多成分药效物质递送的理想方式或载体,进而实现对疾病动态网络多靶点多层次立体靶向调控。笔者提出的方剂纳米体药物发现(formula-derived nanoparticles drug discovery,FDD),创新融合传统中医方剂配伍理论和现代纳米技术方法,可实现PDD和TDD的优势结合,为多靶点药物技术创新与新药发现提供新策略和新方案,有助于大幅度提高多靶点复方药物研发的成功率。展开更多
基金supported by the National Natural Science Foundation of China(Nos.81873195,32471458,and 82473933)the Applied Basic Research Program of Liaoning Province(No.2023JH2/101300103,China)+4 种基金the Liaoning Revitalization Talents Program(No.XLYC1907113,China)Chongqing Talents Program(cstc2022ycjh-bgzxm0111,China)the Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0411)Science and Technology Research Program of Chongqing Municipal Education Commission(KJZD-K202312802,China)the Distinguished Young Scholars in Dalian(2022RJ19,China).
文摘Acute kidney injury(AKI)is a critical clinical condition characterized by rapid renal function decline,with high morbidity,mortality,and healthcare costs.Traditional Chinese medicine(TCM)has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models.Scutellaria barbata D.Don(SB)and Scleromitrion diffusum(Willd.)R.J.Wang(SD),a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities.Using advanced chromatographic separation technology,we enriched the effective fractions of water extracts from SB-SD,obtaining selfassembled herbal nanoparticles(SB and SD nanoparticles,SSNPs)rich in flavonoids and terpenoids.These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Oral administration of SSNPs in mice resulted in absorption into the bloodstream,formation of a protein corona,reduced macrophage phagocytosis,and enhanced bioavailability and renal targeting.Furthermore,we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids.Kinetic studies and in situ transmission electron microscopy(in situ TEM)revealed that these compounds selfassemble via supramolecular forces like hydrogen bonding andπ-πinteractions,forming stable nanostructures.This study elucidates the renoprotective effects and mechanisms of SB and SD,and provides a novel approach for the development of TCM-based nanomedicines,highlighting the potential of nanoTCM in AKI treatment.
文摘目前新药研发高投入高失败率的“反摩尔定律(Eroom′s Law)”提示,现有药物研发将复杂人体系统简化为可研究模型(还原论方法)到最终回归复杂人体系统验证效果(系统论方法)存在转化研究上的巨大鸿沟。近年来全球创新药研发策略发生了两个重大变化:一是希望将表型药物发现(phenotypic drug discovery,PDD)和靶点药物发现(target-based drug discovery,TDD)结合起来以加速创新药研发,二是更加关注多靶点药物设计(multi-target drug design,MTDD)及其对疾病动态网络系统调节的重要性。研究发现,中医方剂及其组成药物衍生的方剂纳米体(formula-derived nanoparticles of TCM,FDN),包括中药外泌体(TCM-Exo)、中药汤剂体(TCM-Deco)、中药碳量子点(TCM-CDs)、中药成分本草体(TCM-Benc)等自组装纳米聚集体,可作为中药多成分药效物质递送的理想方式或载体,进而实现对疾病动态网络多靶点多层次立体靶向调控。笔者提出的方剂纳米体药物发现(formula-derived nanoparticles drug discovery,FDD),创新融合传统中医方剂配伍理论和现代纳米技术方法,可实现PDD和TDD的优势结合,为多靶点药物技术创新与新药发现提供新策略和新方案,有助于大幅度提高多靶点复方药物研发的成功率。
