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Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.
Tang, Xin; Wang, Chuanxi; Wang, Lei; Ren, Feifei; Kuang, Runqiao; Li, Zhenhua; Han, Xue; Chen, Yiming; Chen, Guodong; Wu, Xiuqing; Liu, Jie; Yang, Hengwen; Liu, Xingzhong; Wang, Chen; Gao, Hao; Yin, Zhinan.
Affiliation
  • Tang X; 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.
  • Wang C; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Wang L; 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 Mi
  • Ren F; Department of Respirology, Capital Medical University, Beijing 100069, China.
  • Kuang R; Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an 710004, China.
  • Li Z; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Han X; 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 Mi
  • Chen Y; 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.
  • Chen G; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Wu X; 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 Mi
  • Liu J; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Yang H; 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 Mi
  • Liu X; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Wang C; Department of Respirology, Capital Medical University, Beijing 100069, China.
  • Gao H; Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China.
  • Yin Z; State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China.
Acta Pharm Sin B ; 13(9): 3930-3944, 2023 Sep.
Article in En | MEDLINE | ID: mdl-37719372
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Acta Pharm Sin B Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Acta Pharm Sin B Year: 2023 Document type: Article Affiliation country: