Aromatic compounds and organic acids identified from Ganoderma formosanum exhibit synergistic anti-melanogenic effects

Chen-Che Hsieh ^{a, 1}, Chih-Yao Hou ^{b, 1}, Hsiao-Yun Lei ^a, Darin Khumsupan ^c, Huey-Jine Chai ^d, Pek-Kui Lim ^e, Cheng-Chih Hsu ^f, Sz-Jie Wu ^g, Kai-Wen Cheng ^f, Yi-Chen Chen ^{h, i*}, Kuan-Chen Cheng ^{a, c, j, k*}

a. Institute of Food Science Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.

b. Department of Seafood Science, College of Hydrosphere, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan. R.O.C.

c. Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.

d. Seafood Technology Division, Fisheries Research Institute, Ministry of Agriculture, Keelung 20246, Taiwan. R.O.C.

e. School of Food Studies and Gastronomy, Taylor's University, Subang Jaya, Selangor 47500, Malaysia.

f. Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan. R.O.C.

g. Department of Horticulture and Landscape Architecture, National Taiwan University, Taipei, Taiwan. R.O.C.

h. Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan. R.O.C.

i. The Master Program in Global Agriculture Technology and Genomic Sciences, International College, National Taiwan University, Taipei 106, Taiwan

j. Department of Optometry, Asia University, 500, Lioufeng Rd., Wufeng, Taichung, Taiwan. R.O.C.

k. Department of Medical Research, China Medical University Hospital, China Medical University, 91, Hsueh-Shih Road, Taichung, Taiwan. R.O.C.

This study reveals the anti-tyrosinase activity of Ganoderma formosanum extracts, pinpointing compounds including gluconic acid, mesalamine, L-pyroglutamic acid, esculetin, 5-hydroxyindole, and salicylic acid, as effective melanin production inhibitors in melanoma cells and zebrafish embryos. Furthermore, multiple molecular docking simulations provided insights into interactions between the identified compounds and tyrosinase, increasing binding affinity up to -16.36 kcal/mol. The enhanced binding of identified compounds to tyrosinase facilitated synergistic inhibitory effects on melanin production. This study highlights the potential of GFE-EA as a source of natural tyrosinase inhibitors and contributes to understanding the role of active compounds extracted from G. formosanum.