Anti-Inflammatory Effects of Metabolites from Antarctic Fungal Strain sp. SF-7343 in HaCaT Human Keratinocytes.

Chemical investigation of the Antarctic fungi sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (), altenusin (), alternariol (), and altenuene (). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds and inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds and also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds and inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound , but not compound , significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.