In:
Chinese Journal of Chemistry, Wiley
Abstract:
Psoriasis is a chronic immune‐mediated inflammatory skin disease and the TNF‐ α is 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, (3 β ,5 α ,6 α ,22 E )‐5,6‐epoxy‐3‐hydroxyergosta‐8,22‐dien‐7‐one ( 3 ) and calvasterol B ( 4 ), were isolated 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 pathways 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‐ α induced L929 cells death model, with the EC 50 values of 49.85, 46.75 and 4.99 μmol/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‐ α in 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‐ α inhibitory agents in the clinical treatment of psoriasis.
Type of Medium:
Online Resource
ISSN:
1001-604X
,
1614-7065
DOI:
10.1002/cjoc.202300649
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2144352-X
SSG:
6,25
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