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

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.

Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK‐mediated MITF degradation

“…A number of reports have demonstrated the activation of p38 pathway induces MITF expression and contributes to pigmentation . However, Bellei et al reported that p38 suppress pigmentation through proteasomal degradation of tyrosinase . In our current research, we demonstrated that ISL inhibited melanogenesis and melanosome transport mainly via EKR‐mediated MITF degradation.…”

“…On one hand, several reports have demonstrated the activation of p38 pathway induces MITF expression and contributes to pigmentation . On the other hand, p38 was found to suppress pigmentation via proteasomal degradation of tyrosinase …”

Lecithin-Based Dermal Drug Delivery for Anti-Pigmentation Maize Ceramide

“…Melanin content in the mouse cells was measured following the methodology of a previous study [39], with slight modifications. Mouse melanoma B16 4A5 cells were seeded in a six-well plate (6.7 × 10 3 cells/cm 2 ) and cultured for 24 h in the complete medium.…”

Molecular Targeting of HuR Oncoprotein Suppresses MITF and Induces Apoptosis in Melanoma Cells

“…For example, Slominski et al reported melanogenesis regulated HIF-1α and HIF-1α-regulated target genes are involved in angiogenesis and cellular metabolism [ 76 ]. Similarly, the involvement of cyclic adenosine monophosphate (cAMP) and response binding protein element (CREB) in MITF activation and subsequent upregulation of melanogenesis-regulated gene coding for tyrosinase has been reported [ 77 , 78 ]. Since our study showed a link between HuR and MITF and that HuR is known to regulate HIF-1α and HIF-1α-regulated target genes such as VEGF, it will be of interest to investigate the role of HuR in melanogenesis and melanogenesis regulated tyrosinase in melanoma.…”