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Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

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Pubmed体系：

收录情况： ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Tang Xin[1,2] * ; Wang Chuanxi[3] * ; Wang Lei[4,5] * ; Ren Feifei[2] ; Kuang Runqiao[3] ; Li Zhenhua[1,2] ; Han Xue[3] ; Chen Yiming[2] ; Chen Guodong[3] ; Wu Xiuqing[2] ; Liu Jie[4] ; Yang Hengwen[2] ; Liu Xingzhong[6] ; Wang Chen[4] ; Gao Hao[3] ; Yin Zhinan[1,2] ;
机构： [1]Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China. [2]Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China. [3]Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China. [4]Department of Respirology, Capital Medical University, Beijing 100069, China. [5]Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an 710004, China. [6]State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China.
出处：
DOI： 10.1016/j.apsb.2023.03.017
ISSN：

关键词： Aureane-type sesquiterpene tetraketides IL-17A Experimental autoimmune encephalomyelitis Pulmonary hypertensio

摘要：
Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I (1, 4-11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

基金：
National Key Research and Development Program of China (2018YFA0903200, 2018YFA0903201, and 2020YFA0803502), the National Natural Science Foundation of China (81925037, U22A20371, 31830021, 32030036, and 82270055) and the 111 Project (B16021, China). National High-level Personnel of Special Support Program (2017RA2259, China), Guangdong International Science and Technology Cooperation Base (2021A0505020015, China), Innovative and Research Teams Project of Guangdong Higher Education Institution (2021KCXTD001, China), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y036, China), and Guangdong Natural Science Funds for Distinguished Young Scholar (2021B1515020065, China).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 化学
小类 | 1 区 药学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China. [2]Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
共同第一作者：
通讯作者：
通讯机构： [1]Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China. [2]Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
推荐引用方式(GB/T 7714)：
Tang Xin,Wang Chuanxi,Wang Lei,et al.Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity[J].Acta Pharmaceutica Sinica B.2023,13(9):3930-3944.doi:10.1016/j.apsb.2023.03.017.
APA：
Tang Xin,Wang Chuanxi,Wang Lei,Ren Feifei,Kuang Runqiao...&Yin Zhinan.(2023).Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.Acta Pharmaceutica Sinica B,13,(9)
MLA：
Tang Xin,et al."Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity".Acta Pharmaceutica Sinica B 13..9(2023):3930-3944

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