抗菌-抗炎双功能穿龙薯蓣天然产物靶向调节蛋白质翻译后修饰的活性评价及机制研究  

Activity evaluation and mechanism study of antibacterial-anti-inflammatory bifunctional Dioscoreae Nipponicae Rhizoma natural components targeting regulatory protein posttranslational modification

作　　者：沈如旭 叶子晨 赵嘉琦 张倩[3] 汤海峰[3] 曲迪 SHEN Ru-xu;YE Zi-chen;ZHAO Jia-qi;ZHANG Qian;TANG Hai-feng;QU Di(School of Life Sciences,Liaoning University,Shenyang 110036,China;Department of Health Service,Medical Service Training Base,Air Force Medical University,Xi'an 710032,China;Department of Chinese Materia Medica and Natural Medicines,School of Pharmacy,Air Force Medical University,Xi'an 710032,China;Department of Clinical Pharmacy,General Hospital of Western Theater Command,Chengdu 610000,China;Pancreatic Injury and Repair Key Laboratory of Sichuan Province,General Hospital of Western Theater Command,Chengdu 610000,China)

机构地区：[1]辽宁大学生命科学院,辽宁沈阳110036 [2]中国人民解放军空军军医大学空军卫勤训练基地,卫生勤务学教研室,陕西西安710032 [3]中国人民解放军空军军医大学药学系,中药与天然药物学教研室,陕西西安710032 [4]中国人民解放军西部战区总医院,临床药学科,四川成都610000 [5]胰腺损伤与修复四川省重点实验室,四川成都610000

出　　处：《药学学报》2024年第11期2981-2989,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金(82304573);中国博士后基金会特别资助(曲迪);陕西省重点研发计划(2023-YBSF-514);西部战区总医院院管课题(2021-XZYG-B14)。

摘　　要：细菌耐药现象日益严重亟需研发新的抗菌物质。天然产物作为一种重要的药物研发资源,其能够通过调节与细菌感染和炎症反应相关的蛋白质翻译后修饰来发挥作用,这为抗菌新药物的研发提供宝贵的化合物库。本研究从穿龙薯蓣中分离鉴定的薯蓣皂苷和薯蓣皂苷元均具有一定的抗菌活性,且对革兰阳性菌(G^(+))的抗菌活性优于革兰阴性菌(G^(-))。对比两种成分,薯蓣皂苷元的活性强于薯蓣皂苷。体内实验证实薯蓣皂苷元相比于薯蓣皂苷对MRSA感染脓毒症小鼠具有更好的保护作用,能够提高感染小鼠生存率、降低感染脏器菌落数、降低感染脏器病理损伤、降低小鼠体内炎症因子水平。体内实验获得中国人民解放军空军军医大学动物伦理委员会批准(批准号:20230188)。网络药理学靶点预测显示天然产物薯蓣皂苷元能够靶向体内炎症通路,并可能通过调节蛋白质翻译后修饰在细菌感染中发挥抗菌和抗炎双重活性。The phenomenon of bacterial drug resistance is becoming more and more serious.Natural products,as an important resource for drug discovery,can play a role by regulating protein post-translational modifications related to bacterial infection and inflammatory responses.This provides a valuable compound library for the research and development of new antibacterial drugs.In this present research,dioscin and diosgenin were isolated and identified from Dioscorea nipponica Rhizoma,which both exhibited antibacterial activities,with stronger inhibitory on Gram-positive bacteria(G^(+))than Gram-negative bacteria(G^(-)).Compared these two compounds,diosgenin showed stronger antibacterial activity than dioscin.In vivo experiments confirmed that diosgenin provided better protection against MRSA-induced sepsis in mice compared to dioscin,which could significantly improve survival rates,reduce bacterial colony counts in infected organs,alleviate pathological damage,and decrease inflammatory cytokine levels in mice.The in vivo study was approved by the Animal Ethics Committee of the PLA Air Force Military Medical University(Grant No.20230188).Network pharmacology results also revealed that diosgenin could target inflammatory pathways,exerting dual antibacterial and anti-inflammatory activities during bacterial infection therapy.

关 键 词：天然产物 穿龙薯蓣 抗菌抗炎 脓毒症 靶点预测 蛋白质翻译后修饰 

分 类 号：R914[医药卫生—药物化学]