Antimelanogenesis Activity of Hydrolyzed Ginseng Extract (GINST) via Inhibition of JNK Mitogen‐activated Protein Kinase in B16F10 Cells

Abstract

GINST is a hydrolyzed ginseng extract produced by an in vitro process that imitates the metabolic function of bacteria in the human digestive track and has approved by the Ministry of Food and Drug Safety of Korea for the management of postprandial hyperglycemia. Additionally, GINST has been reported to have other physiological functions including anti-aging and antioxidant effects. The objectives of this study are to compare the antimelanogenic effects of fresh ginseng extract (FGE) and GINST extract and to elucidate the functional mechanism. The concentration of total ginsenosides in FGE and GINST was measured using ultraperformance liquid chromatography with a C18 column. B16F10 cells were treated with FGE and GINST for 72 h to assess melanin content, tyrosinase activity, and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase-related protein-1 (TRP-1). The activity of kinases involved in mitogen-activated protein kinase (MAPK) signaling, such as extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen-activated protein kinases (p38), were measured using western blots. While neither FGE nor GINST inhibited the activity of mushroom tyrosinase directly, GINST decreased melanogenesis and tyrosinase activity markedly. Furthermore, our results indicate that GINST downregulated the levels of MITF and TRP-1 possibly by suppressing JNK signaling. We concluded that, when compared to FGE, GINST has a superior antimelanogenic effect mediated by the downregulation of MITF, TRP-1, and intracellular tyrosinase activity via the JNK signaling pathway. Thus, we suggest that GINST has the potential to be used as a novel skin whitening agent.

Anti-melanogenic and Anti-oxidant Activities of an Ethanolic Extract of Kummerowia striata and its active compounds, p-coumaric acid and quercetin

“…Skin pigmentation is mostly caused by melanin cells in the basal layer of the skin, and is stimulated by UV radiation and anti-pigmentation compounds. The stimulated keratinocytes secrete α-MSH, a small peptide hormone, (14). UV exposure induces melanin production resulting in hyperpigmentation [15].…”

Soyasaponin Ag inhibits α-MSH-induced melanogenesis in B16F10 melanoma cells via the downregulation of TRP-2

“…Indeed, MITF plays a crucial role in melanogenesis as the master regulator of tyrosinase, TRP-1 and TRP-2 expression (30). The hydrolyzed ginseng extract, was found to downregulate MITF and TRP-1 expression B16F10 cells, but only indirectly to attenuate cellular tyrosine activity (31). Moreover, the coumarin derivative, osthol, was found to decrease tyrosinase, TRP-1 and TRP-2 expression, but not to modulate tyrosinase activity (32).…”

Anti-Melanogenic Effects of Hydroxyectoine via MITF Inhibition by JNK, p38, and AKT Pathways in B16F10 Melanoma Cells

“…Recent studies linked the phosphorylation of p38 and JNK in MAPK signaling pathways to the upregulation of melanogenesis via increased MITF expression. 7,8 As shown in Figure 7, hydroxyectoine suppressed the phosphorylation of p38 and JNK, especially at the highest concentration (1000 µM). The results suggested that hydroxyectoine inhibits the expression of MITF by suppressing p38 and JNK phosphorylation, which downregulates melanogenesis.…”

“…On the other hand, increased AKT phosphorylation in the AKT signaling pathway has been reported to inhibit melanin production. [7][8][9] Recent studies have sought to develop tyrosinase inhibitors and biological reductants, such as kojic acid, arbutin, hydroquinone, and ascorbic acid, to treat hyperpigmentation and pigmented diseases. 10,11 However, tyrosinase inhibiting whitening agents have some side effects that include cytotoxicity, low stability to oxygen and water, and cutaneous irritation and dermatitis.…”