Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

Abstract

Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

Rhodiola plants: Chemistry and biological activity

“…Rhodiola rosea B16F0 cells 1 Suppressed melanin synthesis and tyrosinase activity 2 Inhibited TRP-1 and tyrosinase expression 3 Inhibited MC1R/ CREB/ GSK3b/MITF [74,75] Rhodiola rosea extract/ L-carnosine-associated compound Human skin 1 Reduced transepidermal water loss (TEWL) 2 Elevated the skin barrier function 3 Positive subjective response [65] Rhodiola rosea extract/ L-carnosine-associated compound Keratinocytes 1 Promoted the release of proopiomelanocortin peptides 2 Restored to normal the increased levels of neuropeptides and cytokines [65] Rhodiola imbricata SD rats 1 Promoted wound healing 2 Promoted cellular proliferation 3 Increased collagen synthesis 4 Increased the DNA, protein, hydroxyprolin, and hexosamine in granulation cells 5 Antioxidant and decrease lipid peroxidation [38] Rhodiola crenulata extract Propionibacterium acnes antibiofilm activity against Propionibacterium acnes [66] Salidroside B16F0 cells Suppressed melanin synthesis and tyrosinase activity, but no effect on the expression of MC1R, MITF, TRP-1, or TRP-2 [74,78,79] Tyrosol B16F0 cells 1 Suppression of melanin synthesis and tyrosinase activity 2 Suppressed the expression of MC1R and TRP-1, but not TRP-2 and MITF [78] j o u r n a l o f f o o d a n d d r u g a n a l y s i s x x x ( 2 0 1 5 ) 1 e1 1 inhibition of HIF-1a [52]. Rhodiola sachalinensis and salidroside protected liver tissue from oxidative-stress-induced damage.…”

A Multimodal Assessment of Melanin and Melanocyte Activity in Abnormally Pigmented Hypertrophic Scar

“…Alpha-MSH is known to bind the melanocortin 1 receptor (MC1R) leading to downstream expression of tyrosinase, required for the production of melanin 24 . To investigate melanocyte-stimulating activity, primary antibody to α-MSH was used in immunofluorescent staining of hyper- and hypopigmented scar samples.…”

“…Some of these secretion factors act in an autocrine fashion, with melanocyte inhibition occurring via IL-1, IL-6, and TNF-α, but stimulation via eicosanoids and α-MSH 6,30 . Alpha-MSH acts on MC1R, which activates micropthalmia-associated transcription factor, leading to the expression of tyrosinase, a necessary enzyme for melanin production 24 . Activation of the MC1R/α-MSH signaling pathway has been associated with regulation of both inflammation and the extracellular matrix environment 9 .…”

The mixture of glycitin and TDB (3-(2,4,6-trimethoxyphenyl)-2,3-dihydro-1H-benzo[f]chromen-1-one) could ameliorate skin ageing by anti-wrinkle and anti-melanogenesis effects in dermal fibroblasts and melanocytes

“…Melanocytes are the main source of melanin production in human skin (Wen et al, 2013). Natural compounds have been reported to be used in therapy to reduce melanogenesis by inhibiting melanocyte viability (Delijewski et al, 2014).…”