Manassantin A inhibits cAMP-induced melanin production by down-regulating the gene expressions of MITF and tyrosinase in melanocytes

College of Pharmacy, Yeungnam University, Kyungsan, Korea College of Pharmacy, Chungbuk National University, Cheongju, Korea College of Pharmacy, Chungnam National University, Daejeon, Korea.
Experimental Dermatology (Impact Factor: 3.76). 05/2011; 20(9):761-3. DOI: 10.1111/j.1600-0625.2011.01296.x
Source: PubMed


Microphthalmia-associated transcription factor (MITF) is inducible in response to cAMP through the cAMP-responsive element-binding protein (CREB) and plays a pivotal role in the melanocyte-specific expression of tyrosinase or tyrosinase-related proteins (TRPs) for melanin biosynthesis. Manassantin A from Saururus chinensis inhibits cAMP-induced melanin production in B16 melanoma cells. Here, we focused on molecular basis of the antimelanogenic activity. Manassantin A consistently inhibited the cAMP elevator 3-isobutyl-1-methylxanthine (IBMX)- or dibutyryl cAMP-induced melanin production in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or TRP1 gene. Moreover, manassantin A suppressed MITF induction through IBMX-activated CREB pathway, directly inhibiting the Ser-133 phosphorylation of CREB. However, manassantin A did not affect IBMX-increased cAMP levels in these cells but also other cAMP-dependent melanogenic pathways through post-translational modifications of MITF. This putative molecular mechanism of manassantin A in the inhibition of melanin production suggests its pharmacological potential in skin hyperpigmentation.

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Available from: Jong Keun Son, Oct 20, 2014
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    • "Although the detailed mechanism underlying this effect remains elusive, it was hypothesized that manassantin A affects expression of genes regulatory for HIF-1α accumulation. Indeed, manassantin A has been reported to affect expression of a variety of genes (e.g., ICAM-1, MITF), and is also known to suppress the NF-κB transcriptional activity [23], [24]. Interestingly, manassantin A was also reported to inhibit activation of multiple signaling pathways such as pathways mediated by ERK, p38, JNK and STAT3 [25], [26]. "
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    ABSTRACT: Objectives : The purpose of this study was to investigate the melanogenesis inhibition effect of Saururus chinensis BAILL (SC) on in B16F10 melanoma cells. Methods : SC was fractionated ethanol extract by the hexane, ethyl acetate, butanol and water. We confirmed the inhibitory effect of tyrosinase activity and melanogenesis of all fraction samples. Results : Hexane fraction of Saururus chinensis BAILL (HSC), ethyl acetate of SC (ESC), and butanol of SC (BSC) were discovered to inhibit tysoinase activity and melanogenesis in the absence or presence of -MSH. However, water fraction of SC (WSC) did not affect tyrosinase activity and melanogenesis. In addition, all fractions did not inhibit the catalytic activity of cell-free tyrosinase from B16F10 melanoma cell lines. Conclusions : These results suggest that HSC, ESC and BSC reduce pigmentation by indirectly regulating tyrosinase.
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