基于化学计量学和COX-2抑制活性筛选红树共生放线菌中防治药源性听力损失成分  

Screening of components from a mangrove symbiotic actinomycete against druginduced hearing loss based on chemometrics and COX-2 inhibition activity

作　　者：肖素平 钱锦花 温鼎声 许园 陈钢[3] 张明 温露 Xiao Suping;Qian Jinhua;Wen Dingsheng;Xu Yuan;Chen Gang;Zhang Ming;Wen Lu(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006;Guangdong Sunho Pharmaceutical Co.,Ltd.,Zhongshan 528437;Center for Drug Research and Development,Guangdong Pharmaceutical University,Guangzhou 510006)

机构地区：[1]广东药科大学药学院,广州510006 [2]广东星昊药业有限公司,中山528437 [3]广东药科大学新药研发中心,广州510006

出　　处：《中国抗生素杂志》2024年第7期795-803,共9页Chinese Journal of Antibiotics

基　　金：广东省自然科学基金(No.2021A1515012230);广州市基础与应用基础研究项目(No.202201010721);粤澳科技创新联合资助项目(No.2022A0505020014)。

摘　　要：目的利用代谢组学技术和药源性聋细胞模型寻找红树共生放线菌链霉菌属Streptomyces sp.(No.1624117)代谢产物中防治药源性听力损失成分。方法从菌株粗提物中筛选具有抗炎活性的极性分段样,采用超高效液相色谱-串联质谱法(UPLC-MS)对菌株粗提物和活性分段样的化学成分进行数据采集;通过主成分分析法(PCA)与正交偏最小二乘法-判别分析法(OPLS-DA)进行多元统计学分析,筛选差异成分;经过柱层析和高效液相色谱(HPLC)定点分离目标差异点,利用核磁和质谱鉴定结构;最后通过顺铂诱导的HEI-OC1细胞损伤模型考察化合物对耳蜗毛细胞的保护作用。结果代谢组学分析有38个差异代谢物,结合抗炎活性测定结果,分离纯化出6个化学成分并确定了结构。在顺铂诱导的HEI-OC1细胞损伤模型中,化合物1,2,3,4和6均显示出对耳蜗毛细胞具有保护作用。结论本研究建立了一种基于代谢组学技术挖掘放线菌代谢产物中防治药源性听力损失成分的方法,为寻找防治听力损失活性化合物提供了新途径。Objective Metabolomics technology and a drug-induced cell injury model of hearing loss were used to screen the metabolites of the mangrove-derived actinomycete Streptomyces sp.(no.1624117).Methods Polar segmental samples with anti-inflammatory activity were screened from the crude extract of strain 1624117,and collected by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS).The metabolic profiles and chemical compositions were clustered differently by multivariate statistical techniques such as principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA),and their differential chemical compositions were explored.The target compounds were isolated by column chromatography and semi-preparative HPLC,identified by nuclear magnetic resonance and mass spectrometry.Finally,a cisplatin induced HEI-OC1 cell injury model was used to investigate the protective effect of the compounds on cochlear hair cells.Results The UPLC characteristic spectrum of Streptomyces sp.(no.1624117)was established to identify 38 differential markers,respectively.Six compounds were identified based on the results of their anti-inflammatory activity,and their structures were determined.In the cisplatin induced HEI-OC1 cell injury model,all compounds showed protective effects on cochlear hair cells except compound 5.Conclusion In this study,a metabolomic method was established to mine drug-induced hearing loss components from actinomycetes metabolites,which provided a new way to search for active compounds for the prevention and treatment of hearing loss.

关 键 词：共生放线菌 液相色谱-质谱联用 代谢组学 炎症 药源性听力损失 

分 类 号：R978.1[医药卫生—药品]