SRS27,a semisynthetic diterpenoid lactone,inhibits airway inflammation and hyper-responsiveness via NF-κB pathway in an allergic mouse asthma model

作     者：Jonathan Chee Woei LIM Fera Yiqian GOH Sreenivasa Rao SAGINEEDU Audrey Chee Hui YONG Shiran Mohd SIDIK Nordin Haji LAJIS Wai-Shiu Fred WONG Johnson STANSLAS 

作者机构：Pharmacotherapeutics UnitDepartment of MedicineFaculty of Medicine and Health SciencesUniversiti Putra Malaysia Department of PharmacologyYong Loo Lin School of MedicineNational University Health System Laboratory of Natural ProductsInstitute of BioscienceUniversiti Putra Malaysia Faculty of PharmacySegi University College 9Jalan Teknologi Histopathology UnitDepartment of PathologyFaculty of Medicine and Health SciencesUniversiti Putra Malaysia Immunology ProgramLife Science InstituteNational University of Singapore 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2015年第29卷第S1期

页      面：53-53页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：The project supported by grant(BMRC/09/1/21/19/595)from the BioMedical Research Council of Singapore Research University Grant Scheme(RUGS)(04-02-12-2017RU)from the Ministry of Higher Education of Malaysia 

主　　题：NF-κB A549cell line andrographolide analogues nitr 

摘      要：Andrographis paniculata contains two main diterpenoid constituents,andrographolide(AGP)and 14-deoxy-11,12-didehydroandrographolide(DDAG),which were found to exhibit antiasthma effects in a mouse asthma ***,due to inadequacies of both compounds in terms of drug-likeness,DDAG analogues were semisynthesised to tackle these *** objective of the study was to investigate the potential of DDAG analogues as new antiasthma *** the analogues,(SRS27)was proven to inhibit cysteinyl leukotrienes(CysLT)and nitric oxide(NO)synthesis in mouse macrophages,like ***,on the other hand,failed to exhibit such ***27 is less cytotoxic than AGP,suggests that a simple chemical modification of DDAG produces a compound with CysLT and NO inhibitory activites similar to AGP while maintaining toxicity profile similar to *** is interesting to note that other analogues such as SRS28,SRS49,SRS76 and SRS83 with chemical modifications on the same carbon numbers 3 and 19 of DDAG were unable to show inhibition of CysLT and NO ***,the potential anti-inflammatory effect of SRS27 was investigated in ovalbumin(OVA)-induced mouse asthma *** compound was administered in a prophylactic manner and showed a substantial decrease in mouse asthma model ***27 at 3mg·kg-1 significantly reduced OVA-induced total cell such as macrophages,eosinophils,lymphocytes and neutrophils,as well as inflammatory cytokines such as IL-4,IL-5,IL-13 and eotaxin in bronchoalveolar lavage BAL *** compound also suppressed serum IgE *** addition,SRS27 suppressed mucus hyper-secretion and expression of inflammatory mediators such as TNF-α,MCP-1,Muc5 ac,RANTES,IL-33 and ***27 is the first known DDAG derivative tested positive in mouse asthma model and as such SRS27 could serve as a prototype prophylactic agent.