Page 245 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-62

Discovery of isochromophilone IV from Penicillium sclerotiorum: A Marine

natural product with anti-angiogenic potential

,1
1
Shan-Chi Liu, Shih-Wei Wang*

1 Institute of Biomedical Sciences, Mackay Medical University, New Taipei City 252005,
Taiwan
* E-mail: shihwei@mmu.edu.tw

Abstract
Discovery of bioactive natural products from Chinese herbal medicines, medicinal plants,
and marine organisms represents a promising strategy for the development of new drug
candidates. Marine microorganisms, including bacteria, microalgae, and fungi, are particularly
attractive sources of novel bioactive metabolites for drug discovery. However, the anti-
angiogenic potential of marine-derived natural products remains largely unexplored. In this
project, we identified isochromophilone IV from the edible alga-associated fungus Penicillium
sclerotiorum isolated from Grateloupia sp. through bioassay-guided fractionation. Our
experiments demonstrated that isochromophilone IV significantly inhibited endothelial
progenitor cell (EPC) tube formation and migration in a concentration-dependent manner,
without detectable cytotoxicity. Furthermore, isochromophilone IV suppressed in vivo
angiogenesis in zebrafish embryos. Mechanistic studies revealed that isochromophilone IV
downregulated the expression of angiogenesis-related proteases (kallikrein-10, MMP-13, and
uPA), as determined by protease antibody array. Integrated miRNA analysis further suggested
that isochromophilone IV may regulate these proteases by upregulating miR-378i and miR-
1260a in EPCs. Taken together, these findings highlight isochromophilone IV as a novel marine
fungus-derived metabolite with potent anti-angiogenic activity and warrant further clinical
investigation of its therapeutic potential.

Keywords: Anti-angiogenic; Isochromophilone IV; kallikrein-10; Matrix metallopeptidase 13
(MMP-13); uPA