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

Abstract

Isoliquiritigenin (ISL), a flavonoid component from the hydrolysis products of licorice root. It has been reported that ISL inhibited melanogenesis by suppressing the tyrosinase activity in human melanocytes. Recently, ISL was found to induce melanin degradation in human epidermal keratinocytes. However, the role of ISL in pigmentation is not fully understood. In the current study, we aimed to investigate the effects of ISL on pigmentation, and further explored the underlying mechanism. Our results suggested that ISL suppressed basal and α‐MSH‐, ACTH‐ and UV‐induced melanin synthesis, in addition to inhibiting melanocyte dendricity and melanosome transport. ISL played these roles mainly by activating the extracellular signal‐regulated protein kinase pathway. Once activated, it induced microphthalmia‐associated transcription factor degradation and decreased the expression of tyrosinase, TRP‐1, DCT, Rab27a and Cdc42, finally inhibited melanogenesis, melanocyte dendricity and melanosome transport. Our findings suggested that ISL exhibited no cytotoxicity in our research, it may prove quite useful as a safer natural skin‐whitening agent.

Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling

“…Samples (60 μg protein each) were separated using SDS-PAGE before transferring to PVDF membranes (0.20 μm; Millipore, Billerica, MA, United States). Nonspecific binding events were blocked with 5% skim milk for 90 min ( Lv et al, 2020 ). Membranes were subsequently incubated with the appropriate primary antibodies for rabbit anti-5HT 1A receptor (at a dilution of 1:1000; Abcam, United States), anti-5HT 1B receptor (at a dilution of 1:1000; Abcam, United States), anti-5HT 7 receptor (at a dilution of 1:1000; Abcam, United States), anti-pCREB (at a dilution of 1:1000; Abcam, United States), anti-BDNF (at a dilution of 1:1000; Abcam, United States), and anti-β-Actin (at a dilution of 1:5000; Abcam, United States) overnight at 4°C.…”

Natural Chalcones in Chinese Materia Medica: Licorice

“…Other Activities. Isoliquiritigenin has been detected to have antiplatelet action [130], protective effect on cerebral ischemia injury [131], and estrogen-like [132], neuroprotective [133], and antimelanogenic [134] activities. Licochalcone A has been demonstrated to possess antispasmodic [135], antileishmanial [136], antimalarial [137], and osteogenic activities [138].…”

Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

“…Threshold cycles were placed in the logarithmic portion of the amplification curve, and the results were normalized to GAPDH. The fold difference between two samples was determined by the delta-delta Cq method (Lv et al, 2020). The primer sequences are presented in Supplement Materials Table I and II.…”

“…Activity and the Expression Levels of Tyrosinase, TRP-1, TRP-2, and MITF Tyrosinase plays an important role in melanogenesis (Wang et al, 2017). MITF is a key activator of the tyrosinase promoter (Lee et al, 2013;Lv et al, 2020). First, we measured the effects of PPIX on cellular and cell-free tyrosinase activity.…”

“…The key enzyme that regulates melanogenesis is tyrosinase, and it acts with tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2) to promote melanogenesis ( Park et al., 2020 ). Microphthalmia-associated transcription factor (MITF), a key activator of the tyrosinase promoter, is a master transcription factor that activates the transcription of pigmentation genes and is required for melanocyte proliferation and survival ( Lee et al., 2013 ; Lv et al., 2020 ), whereas kinesin family member 5b (KIF5b) functions as a motor that regulates outward melanosome transport along microtubules ( Hara et al., 2000 ; Hirokawa et al., 2009 ). >>myosin Va-melanophilin-Ras–related protein Rab-27A (Rab27a) complexes contribute to melanosome transport along actin filaments, while Rab27A-melanophinin complex is responsible for anchoring melanosomes transferred to the cell membrane ( Ohbayashi and Fukuda, 2012 ).…”