Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-?B and JAK2/STAT3 in HaCaT Human Keratinocytes

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients' quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), 5 & PRIME;-methoxy-6-methyl-biphenyl-3,4,3 & PRIME;-triol (2), 3,8,10-trihydroxy-4-methoxy-6-methylbenzocoumarin (3), and alternariol monomethyl ether (4). Additionally, we identified the skin anti-inflammatory composition from the SF-7343 strain. Interleukin-8 and -6 Screening results showed that compound 1 inhibited IL-8 and IL-6 in tumor necrosis factor-alpha/interferon-gamma stimulated HaCaT cells. Compound 1 showed inhibitory effects on MDC and RANTES. It also downregulated the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulated the expression of involucrin. The results of the mechanistic study showed that compound 1 inhibited the nuclear translocation of nuclear factor-kappa B p65 and STAT3. In conclusion, this study demonstrates the potential of the Antarctic fungal strain SF-7343 as a bioactive resource to inhibit skin inflammation, such as AD.

Automated summary

This study discovered four secondary fungal metabolites with anti-inflammatory properties in the Antarctic fungus strain SF-7343, and identified one compound (compound 1) that can inhibit the release of inflammation factors IL-8 and IL-6 in HaCaT cells stimulated with tumor necrosis factor-alpha/interferon-gamma. Compound 1 also showed effects on cell adhesion and involucrin expression regulation.