Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-p...Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus sp.TJ507.Structure elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction tests.Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder reactions.Activity screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control SPD304.Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT cells.In an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic effect.As such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.展开更多
基金supported financially by the National Natural Science Foundation for Distinguished Young Scholars (No.81725021)the National Natural Science Foundation of China (Nos.82003633,82173705 and 31972865)+2 种基金the Natural Science Foundation of Hubei Province (2023AFB791)the Research and Development Program of Hubei Province (2020BCA058)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (WDCM2023010).
文摘Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus sp.TJ507.Structure elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction tests.Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder reactions.Activity screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control SPD304.Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT cells.In an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic effect.As such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.
