Inhibitory Effects of <i>Saururi chinensis</i> Extracts on Melanin Biosynthesis in B16F10 Melanoma Cells

Abstract

Saururus chinensis has been used in folk medicine in Korea for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases. Saururi chinensis extracts (SCE) have demonstrated antiinflammatory and anti-oxidant activities, as well as anti-asthmatic, antihypertensive, anti-angiogenic, and therapeutic activities for atopic dermatitis. However, the inhibitory activity of SCE on the melanogenesis signaling pathway is not completely understood. This study examined the effects of SCE on the melanogenesis signaling pathway activated by α-melanocyte-stimulating hormone (α-MSH). We found that SCE inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 cells. Interestingly, SCE decreased α-MSH-induced tyrosinase activity in B16F10 cells but did not inhibit tyrosinase activity under cell-free conditions. The results of this study indicate that SCE may reduce pigmentation by way of an indirect, nonenzymatic mechanism. We also found that SCE decreased α-MSH-induced microphthalmiaassociated transcription factor (MITF) and tyrosinase expression and induced the activation of extracellular signal-regulated kinase (ERK). These results suggest that the depigmenting effect of SCE may result from downregulation of MITF and tyrosinase expression due to increased ERK activity. Thus, our results provide evidence that SCE might be useful as a potential skin-whitening agent.Key words B16F10 melanoma cell; extracellular signal-regulated kinase; melanogenesis; Saururi chinensis; tyrosinase In mammals, pigmentation results from the synthesis and distribution of melanin in the skin, hair bulbs and eyes. Melanin is a pigmented polymer, which provides photoprotection to the skin against UV radiation. Various hyperpigmented disorders such as melasma can be caused by excessive synthesis of melanin. Melanogenesis comprises many enzymatic oxidation steps in which tyrosine is converted to eumelanin and pheomelanin.1) Tyrosinase, tyrosinase-related protein-1 (TRP-1), and dihydroxyphenylalaminechrome tautomerase (TRP-2) are key enzymes involved in the regulation of melanogenesis.2)The expressions of tyrosinase and TRP1 and TRP2 genes are activated by microphthalmia-associated transcription factor (MITF) through cooperation with protein kinase C (PKC). 3)Tyrosinase catalyses the rate-limiting reaction of the melanogenic process, and melanin production is regulated mainly by the expression and activation of tyrosinase. [3][4][5] Recently, the inhibition of extracellular signal-regulated kinase (ERK) signaling was reported to induce hyperpigmentation by increasing tyrosinase activity, suggesting that the activation of ERK signaling downregulates melanogenesis by inhibiting tyrosinase activity. [6][7][8] These reports show that the improved methods of melanogenesis inhibition do not suppress the activity of tyrosinase as much as they control the tyrosinase upstream signaling pathway related to its activation and expression.Several known natural melanin synthesis inhibitors, including arbutin and koj...

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