Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion

Abstract

Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study the impact of THC on the melanogenic process under stressed conditions. It was demonstrated that THC could effectively inhibit the α-MSH (melanocyte-stimulating hormone) induced melanin production in B16F10 melanoma cells and the expressions of three key enzymes involved with the biosynthetic process of melanin, tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), were all significantly reduced. In addition, an in vitro human keratinocyte cell model was used to investigate the potential protective role of THC on H2O2-induced cytotoxicity. It was found that THC could prevent H2O2-induced oxidative stress based on the results of both the cell viability study and the intracellular ROS (reactive oxygen species) study assessed by the flow cytometry. Last, THC was formulated into a lecithin based nanoemulsion, and an in vitro Franz diffusion cell study using Strat-M® membrane concluded that the nanoemulsion could significantly enhance the membrane permeation compared to the unformatted THC suspension. This research demonstrated the anti-melanogenic benefits of THC on the melanoma and keratinocyte cell models and the topical delivery efficacy could be significantly enhanced using a lecithin based nanoemulsion.

Hyperpigmentation: Looking beyond hydroquinone

“…Besides, it also reduces the expression of three main enzymes associated with the biosynthetic pathway of melanin namely tyrosinase (TYR), tyrosinase‐related protein 1 (TRP‐1), and tyrosinase‐related protein 2 (TRP‐2). Furthermore, it prevents oxidative stress and demonstrates superior anti‐inflammatory properties 19 …”

“…Furthermore, it prevents oxidative stress and demonstrates superior anti-inflammatory properties. 19 In a randomized placebo controlled clinical study, 0.25% THC cream produced a comparable depigmenting effect to 4% HQ cream. THC did not produce any adverse effects, whereas mild-tomoderate adverse effects were seen in subjects using HQ.…”

Explore the multitarget mechanism of tetrahydrocurcumin preventing on UV-induced photoaging mouse skin

“…Long term exposure to ultraviolet radiation will make keratinocytes continuously secrete End1 and Edn3 and accelerate melanocyte proliferation and melanogenesis [ 43 ]. It has been demonstrated in previous cellular studies that THC have a good effect of anti-oxidation and anti-melanin production [ 28 , 44 ]. This time, the same results were observed in our animal experiments.…”

The elastase and melanogenesis inhibitory and anti-inflammatory activities of phosvitin phosphopeptides produced using high-temperature and mild-pressure (HTMP) pretreatment and enzyme hydrolysis combinations

“…Skin, the largest organ in the human body, regulates the temperature and moisture content of the body and acts as a physically and immunologically effective barrier against ultraviolet ( UV ) radiation, pathogenic microorganisms, and chemicals ( Chamcheu et al, 2021 ; Tang et al, 2021 ). When the skin is exposed to excessive stress like UV radiation, reactive oxidative species ( ROS ) are produced and accumulated, leading to skin photoaging and wrinkling ( Lorz et al, 2019 ).…”

“…Also, oxidative stress can cause inflammatory responses by activating the nuclear factor ( NF )-κB and the mitogen-activated protein kinase ( MAPK ) signaling pathway. Cyclooxygenase-2 ( COX-2 ) is one of the enzymes related to photoaging and ROS passing through cellular and nuclear membranes in the keratinocytes, inducing the generation of hydroxyl radicals and causing DNA damage ( Lorz et al, 2019 ; Tang et al, 2021 ).…”