Abstract

Medicinal plants have been used to treat diseases from time immemorial. We aimed to examine the efficacy of the ethyl acetate fraction of Nymphaea nouchali flower extract (NNFE) against melanogenesis process, and the underlying mechanisms in vitro and in vivo. Paper spray ionisation mass spectroscopy and (+) mode electrospray ionisation revealed the presence of seven flavonoids, two spermidine alkaloids, 3,4,8,9,10-pentahydroxy-dibenzo[b,d]pyran-6-one, and shoyuflavone C in NNFE. NNFE (100 µg/mL) significantly inhibited the monophenolase and diphenolase activities of mushroom tyrosinase at 94.90 ± 0.003% and 93.034 ± 0.003%, respectively. NNFE significantly suppressed cellular tyrosinase activity and melanin synthesis in vitro in melan-a cells and in vivo in HRM2 hairless mice. Furthermore, NNFE inhibited tyrosinase (TYR), tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) expression, thereby blocking melanin synthesis. In particular, NNFE suppressed cAMP production with subsequent downregulation of CREB phosphorylation. Additionally, it stimulated MAP kinase phosphorylation (p38, JNK, and ERK1/2) and the proteasomal debasement pathway, leading to degradation of tyrosinase and MITF and the suppression of melanin production. Moreover, selective inhibitors of ERK1/2, JNK, and p38 attenuated NNFE inhibitory effects on melanogenesis, and MG-132 (a proteasome inhibitor) prevented the NNFE-induced decline in tyrosinase protein levels. In conclusion, these findings indicate that NNFE is a potential therapy for hyperpigmentation.

Highlights

  • Melanin protects the skin from ultraviolet (UV)-induced skin damage and plays a crucial role in maintaining skin colour

  • It is important to note that cleavage at the glycosidic O-linkages and the concomitant H-rearrangement led to the elimination of monosaccharide residues, i.e. losses of 162 u, 146 u, 132 u, or 172 u, which allowed the determination of the carbohydrate sequence[23]

  • The current study reported the repressive effects of N. nouchali flower extract (NNFE) on melanin biosynthesis in melan-a cells and the HRM-2 hairless mouse model

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Summary

Introduction

Melanin protects the skin from ultraviolet (UV)-induced skin damage and plays a crucial role in maintaining skin colour. Cheli et al.[11] showed that cAMP activation by α-MSH or forskolin regulated vacuolar ATPase and ion transporters of the solute carrier family This could lead to extensive changes in the ionic equilibrium of the melanocytes, resulting in alkalization of melanosomes, and thereby facilitating melanogenesis. Whitening agents containing strong TYR inhibitors have serious adverse effects and problems, such as highly cytotoxic and unstable to oxygen and water, which limit their application Owing to their modest toxicity and favourable side effect profile, natural ingredients are being considered in the field of cosmetic research and development of safe and efficacious skin depigmenting compounds. To extend the efforts made to develop novel and useful cosmetic ingredients, supplements, and functional foods, the current study designed to explore the effects of N. nouchali flower extract (NNFE) on melanogenesis in a melanocyte cell culture system and the HRM-2 hairless mouse model. We investigated the anti-melanogenic activity of NNFE through the participation of MAP kinase phosphorylation as well as the NNFE-associated proteasomal abasement machinery of TYR to affirm its repression potential in melan-a cells

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