Highlights
- •This manuscript extends the novel function of YH as the anti-melanogenic agents.
- •It is first to report YH could inhibit β-catenin nuclear accumulation and p38 phosphorylation.
- •YH downregulates MITF expression via regulating Wnt/β-catenin and p38/MAPK signal pathways.
Abstract
Background
Yohimbine hydrochloride (YH) is a prescription drug to treat erectile dysfunction.
It also had potential in fighting high blood pressure and diabetic neuropathy as well
as promoting weight loss.
Objective
The aim of the study is to investigate the anti-melanogenic function of yohimbine
hydrochloride and reveal its underlying molecular mechanism.
Methods
B16F10 mouse melanoma cells, Melan-A murine melanocyte, Zebrafish embryos and C57BL/6
mouse ear skins were treated with different concentrations of YH. The extracellular
and cellular melanin content was detected by spectrometry. The expression of microphthalmia-associated
transcription factor (MITF), tyrosinase and the activities of Wnt/β-catenin and p38/MAPK
signal pathways were determined by RT-qPCR, Western blot analysis and immunofluorescent
staining.
Results
Melanin production could be effectively inhibited by YH at the safe concentration
in vitro and in vivo. Q-PCR and WB results showed that the expression of MITF and
tyrosinase were strongly downregulated after YH treatments along with the reduction
of tyrosinase activity. YH markedly inhibited β-catenin nuclear accumulation and p38
phosphorylation in B16F10 cells compared with the untreated controls. Importantly,
the increase of MITF expression induced by β-catenin activator BIO and p38 activator
anisomycin could be fully reversed by YH treatments.
Conclusions
These results indicate that YH can function as an anti-melanogenic agent, at least
in part, by inhibiting Wnt/β-catenin and p38/MAPK signal pathways. Therefore, YH may
be potentially used as a skin-whitening compound for preventing hyperpigmentation
disorders in the future.
Keywords
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References
- Recent advances in understanding the molecular basis of melanogenesis in melanocytes.F1000Research. 2020; 9
- Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation.Int. J. Cosmet. Sci. 2018; 40: 328-347
- Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes.J. Invest. Dermatol. 2013; 133: 2416-2424
- Melanosome degradation in epidermal keratinocytes related to lysosomal protease cathepsin V.Biochem. Biophys. Res. Commun. 2018; 500: 339-343
- Curcumin inhibits melanogenesis in human melanocytes.Phytother. Res. 2012; 26: 174-179
- Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways.J. Dermatol. Sci. 2019; 94: 213-219
- Depigmentation and anti-aging treatment by natural molecules.Curr. Pharm. Des. 2019; 25: 2292-2312
- Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial.Int. J. Impot. Res. 2002; 14: 25-31
- Yohimbine hydrochloride ameliorates collagen type‐II‐induced arthritis targeting oxidative stress and inflammatory cytokines in Wistar rats.Environ. Toxicol. 2017; 32: 619-629
- Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro.World J. Gastroenterol.: WJG. 2008; 14: 2358
- Yohimbine improves lipid and carbohydrate profiles without reduction in body weight in obese leptin-deficient ob/ob mice.J. Pre-Clin. Clin. Res. 2018; 12
- Downregulation of tyrosinase activity in human melanocyte cell cultures by yohimbine.J. Invest. Dermatol. 2000; 115: 130-131
- A zebrafish embryo as an animal model for the treatment of hyperpigmentation in cosmetic dermatology medicine.Medicina. 2018; 54: 35
- Neurokinin-1 receptor is a novel positive regulator of Wnt/β-catenin signaling in melanogenesis.Oncotarget. 2016; 7: 81268
- Syntenin regulates melanogenesis via the p38 MAPK pathway.Mol. Med. Rep. 2020; 22: 733-738
- Plant-based skin lightening agents: A review.J. Phytopharm. 2020; 9: 54-60
- Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways.Exp. Dermatol. 2015; 24: 761-766
- Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels.J. Invest. Dermatol. 2011; 131: 1291-1299
- Dexamethasone enhances the norepinephrine-induced ERK/MAPK intracellular pathway possibly via dysregulation of the α2-adrenergic receptor: Implications for antidepressant drug mechanism of action.Eur. J. Cell Biol. 2010; 89: 712-722
- PKA-GSK3β and β-catenin signaling play a critical role in trans-resveratrol mediated neuronal differentiation in human cord blood stem cells.Mol. Neurobiol. 2018; 55: 2828-2839
- p38 regulates pigmentation via proteasomal degradation of tyrosinase.J. Biol. Chem. 2010; 285: 7288-7299
- Microphthalmia transcription factor is a target of the p38 MAPK pathway in response to receptor activator of NF-κB ligand signaling.J. Biol. Chem. 2002; 277: 11077-11083
Article info
Publication history
Published online: July 03, 2022
Accepted:
June 30,
2022
Received in revised form:
May 31,
2022
Received:
July 28,
2021
Identification
Copyright
© 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
