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

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.

Afiliación

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 en En | MEDLINE | ID: mdl-37719372

RESUMEN

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.

Palabras clave

Aureane-type sesquiterpene tetraketides; Experimental autoimmune encephalomyelitis; IL-17A; Pulmonary hypertension

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