Evaluation of Antimelanogenic Activity and Mechanism of Galangin <i>in Silico</i> and <i>in Vivo</i>

Abstract

Abnormal pigmentation owing to excessive melanin synthesis can result in serious problems such as freckles, age-spots, and melanoma. Tyrosinase inhibitors have been an interesting target for the treatment of hyperpigmentation because tyrosinase is the rate-limiting enzyme in melanin synthesis. The screening for strong tyrosinase inhibitors led to the finding of the flavonoid galangin, which showed notable inhibitory effects on mushroom tyrosinase. The IC 50 value of galangin (3.55 0.39 µM) was lower than that of kojic acid (48.55 1.79 µM), which was used as a positive control. In silico docking simulation and mechanistic studies demonstrated that galangin interacted with the catalytic sites of tyrosinase and competed with tyrosine. In B16F10 melanoma cells stimulated with α-melanocyte stimulating hormone, galangin inhibited tyrosinase activity as well as melanin production. Although high doses of galangin were cytotoxic, no cytotoxic effects were observed at low doses. In addition, the in vivo efficacy of galangin was evaluated in HRM2 melaninpossessing hairless mice. As measured by the skin-whitening index and melanin staining, repeated UVB exposure increased skin melanin synthesis. Galangin application significantly reduced melanogenesis induced by UVB exposure. Collectively, our data indicates that galangin shows strong tyrosinase inhibition activity, which suggests that it may be an effective skin-whitening agent.Key words galangin; melanogenesis; pigmentation; tyrosinase Galangin, a flavonoid compound, is found in high concentrations in Alpinia officinarum and Helichrysum aureonitens.

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Modulation of p38 phosphorylation prevented excessive melanin synthesis through the accelerated degradation of melanogenic enzymes . Norartocarpetin (C 15 H 10 O 6 ), a flavone, which can be found in plants such as A communis , Artocarpus heterophyllus, and Artocarpus dadah was proposed to downregulate MITF expression via JNK‐ and p38‐dependent pathway .…”

“…Norartocarpetin (C 15 H 10 O 6 ), a flavone, which can be found in plants such as A communis , Artocarpus heterophyllus, and Artocarpus dadah was proposed to downregulate MITF expression via JNK‐ and p38‐dependent pathway . ERK and JNK phosphorylation causes MITF ubiquitination and degradation, whereby downregulating melanin biosynthesis . Similar to norartocarpetin A, other compounds such as Morinda citrifolia extract, sesamol (C 7 H 6 O 3 ) of Sesamun indicum L., and jineol (C 9 H 7 O 2 N) of Scolopendra subspinipes also induce phosphorylation of p38 MAPK in melan‐a and B16 cells .…”

“…Penetrability of bioactive compounds plays a major role for their bioavailability in the cells before subsequence action and inhibition to enzyme or melanogenic proteins . In particular, concentration and exposure time of depigmenting compounds play major role in inhibition strength toward melanogenic targets . Mechanism of action for depigmenting activity of one compound can also be varied depending on their molecular structure, size, chemical‐physical property, and even lipophilicity.…”

“…Moreover, TYR pigmentation, melanosome transfer, and phagocytosis of melanosomes by keratinocytes are enhanced in the presence of keratinocyte‐derived growth factor, SCF . On the other hand, the addition of 12‐0‐tetradecanoylphorbol acetate (TPA), cholera toxin (CT), isobutylmethylxanthine (IBMX), and bFGF NHM growth medium led to an increase in intracellular cAMP level and melanocyte proliferation …”

“…78 On the other hand, the addition of 12-0-tetradecanoylphorbol acetate (TPA), cholera toxin (CT), isobutylmethylxanthine (IBMX), and bFGF NHM growth medium led to an increase in intracellular cAMP level and melanocyte proliferation. 31,53,58,73,96 Melanoma cell lines were normally grown in medium such as…”