Abstract

A potential natural melanogenesis inhibitor was discovered in the form of a sesquiterpene isolated from the flowers of Inula britannica, specifically 6-O-isobutyrylbritannilactone (IBL). We evaluated the antimelanogenesis effects of IBL on B16F10 melanocytes and zebrafish embryos. As a result, we found that 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production was reduced in a dose-dependent manner in B16F10 cells by IBL. We also analyzed B16F10 cells that were and were not treated with IBMX, investigating the melanin concentration, tyrosinase activity, mRNA levels. We also studied the protein expressions of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related proteins (TRP1, and TRP2). Furthermore, we found that melanin synthesis and tyrosinase expression were also inhibited by IBL through the modulation of the following signaling pathways: ERK, phosphoinositide 3-kinase (PI3K)/AKT, and CREB. In addition, we studied antimelanogenic activity using zebrafish embryos and found that the embryos had significantly reduced pigmentation in the IBL-treated specimens compared to the untreated controls.

Highlights

  • Melanocyte is a neural crest-derived skin cell that produces the protective pigment melanin [1].Melanin is generated by melanosomes in melanocytes, which are located in the epidermis, and is the substance that affects hair, skin, and eye color in mammals [2]

  • Silica gel chromatography was performed on an ethanol extract of I. britannica

  • Fraction D, which markedly reduced melanin production in B16F10 cells, was subjected to guided by its antimelanogenic effects, leading to the isolation of an active compound [22]. This compound further chromatography guided by its antimelanogenic effects, leading to the isolation of an active was an amorphous powder with ion peakpowder at m/z 337

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Summary

Introduction

Melanocyte is a neural crest-derived skin cell that produces the protective pigment melanin [1].Melanin is generated by melanosomes in melanocytes, which are located in the epidermis, and is the substance that affects hair, skin, and eye color in mammals [2]. Melanin biosynthesis is crucial in the body’s defense against the harmful effects to the skin caused by DNA damage and ultraviolet (UV) radiation [3,4]. Excessive production of melanin due to frequent or excessive exposure to UV radiation can cause abnormal hyperpigmentation as a result of inflammation, age spots, freckles, lentigo senilis, and melasma [5]. UV radiation can cause abnormal hyperpigmentation as a result of inflammation, age spots, freckles, lentigo senilis, and melasma [5]. Present in melanosomes with tyrosinase are tyrosinase-related protein 1 Tyrosinase (TRP1) andserves tyrosinase-related (TRP2), in which arel-tyrosine importantiscatalysts for reactions as a catalyst protein for the process which hydroxylated to (L-DOPA)

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