Attenuation of melanogenesis by Nymphaea nouchali (Burm. f) flower extract through the regulation of cAMP/CREB/MAPKs/MITF and proteasomal degradation of tyrosinase

• Published in: Scientific reports 2018-09, Vol.8 (1), p.13928-14, Article 13928
• Main Authors: Alam, Md Badrul, Ahmed, Arif, Motin, Md Abdul, Kim, Sunghwan, Lee, Sang-Han
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 38/77; 59; 631/154/436; 631/61/54/2295; 64; 64/60; 82; 82/1; 96; 96/1; Acetic acid; Agaricales - enzymology; Alkaloids; Animals; Cyclic AMP - metabolism; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Ethyl acetate; Extracellular signal-regulated kinase; Flavonoids; Flowers; Flowers - chemistry; Hairless; Humanities and Social Sciences; Hyperpigmentation; Hypopigmentation - chemically induced; Kinases; MAP kinase; Mass spectroscopy; Medicinal plants; Melanin; Melanins - biosynthesis; Mice; Mice, Hairless; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - metabolism; Mitogen-Activated Protein Kinases - metabolism; Monophenol Monooxygenase - metabolism; multidisciplinary; Nymphaea - chemistry; Nymphaea nouchali; Phosphorylation; Plant Extracts - pharmacology; Polyphenols - metabolism; Proteasome Endopeptidase Complex - metabolism; Proteasome inhibitors; Proteolysis; Science; Science (multidisciplinary); Signal Transduction - drug effects; Spermidine; Ultraviolet Rays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32303-7

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.