[논문]Acremonidin E produced by Penicillium sp. SNF123, a fungal endophyte of Panax ginseng, has antimelanogenic activities

Kim, Kyuri; Jeong, Hae-In; Yang, Inho; Nam, Sang-Jip; Lim, Kyung-Min

doi:10.1016/j.jgr.2019.11.007

[국내논문] Acremonidin E produced by Penicillium sp. SNF123, a fungal endophyte of Panax ginseng, has antimelanogenic activities 원문보기

Journal of ginseng research = 高麗人參學會誌, v.45 no.1, 2021년, pp.98 - 107

Kim, Kyuri (College of Pharmacy, Ewha Womans University) , Jeong, Hae-In (Department of Chemistry and Nanoscience, Global Top 5 Program, Ewha Womans University) , Yang, Inho (Department of Convergence Study on the Ocean Science and Technology, Korea Maritime and Ocean University) , Nam, Sang-Jip (Department of Chemistry and Nanoscience, Global Top 5 Program, Ewha Womans University) , Lim, Kyung-Min (College of Pharmacy, Ewha Womans University)

Abstract ▼ AI-Helper

Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

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표/그림 (8)

표 Table 1 NMR data of acremonidin E (1, DMSO-d₆)^a
그림 Fig. 1. (A) Chemical structure and (B) COSY and key KMBC correlations of acremonidin E (1).
그림 Fig. 2. Effects of acremonidin E (1) on melanin content and viability of B16F10 cells. (A) Measured melanin content; (B) Cell viability was determined by MTT assay. The cells were treated with arbutin at 50 μg/mL and with 1 at the indicated concentrations for 48 h. Data are presented as the mean ± standard deviation (SD) (n = 4).
그림 Fig. 3. Effects of acremonidin E (1) on dendrite formation in various cell lines. (A) Morphological changes of B16F10 cells; (B) Macroscopic view of MNT-1 cell pellets; (C) Dendrite formation changes in MNT-1/HaCaT coculture cells. The cells were treated with 1 for 24 h, and morphological changes were observed under optical microscopy (400 X). The MNT-1 cell pellets were lysed by RIPA buffer.
그림 Fig. 4. Effects of acremonidin E (1) on mushroom tyrosinase activity. Tyrosinase enzymatic activity was investigated using a mushroom tyrosinase assay with (A) L-tyrosine and (B) L-DOPA (3,4-dihydroxyphenylalanine) as substrates. Data are presented as the ± SD (n = 3).
그림 Fig. 5. Effects of acremonidin E (1) on the mRNA level of B16F10 cells. mRNA expression levels of (A) tyrosinase; (B) TRP-1 in B16F10 cells were determined by real-time PCR. The cells were treated with 1 and bisabolol at the indicated concentrations for 24 h. Data are presented as the mean ± SD (n = 3, *p < 0.05 and **p < 0.01).
그림 Fig. 6. Effects of acremonidin E (1) on protein levels in B16F10 cells. Tyrosinase and TRP-1 protein levels were determined by western blotting. (A) Tyrosinase protein levels; (B) Quantitation of tyrosinase protein level; (C) TRP-1 protein levels; (D) Quantitation of TRP-1 protein level. The cells were treated with 1 at a concentration of 25μL for the indicated times. The quantitation of the western blot band was analyzed by Multi Gauge V3.0 software.
그림 Fig. 7. Effects of acremonidin E (1) on the Melanoderm 3D skin model. (A) Color of 3D human skin tissue model (Melanoderm; MatTek); (B) hematoxylin and eosin (H & E) stained tissues, Fontana-Masson (FM) stained tissues, and MelanA stained tissues; (C) Cell viability was further confirmed in a 3D reconstituted human epidermis model, Keraskin, using MTT assay. Data are presented as the mean ± SD (n = 3).

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