Oxyresveratrol-induced Activation of Nrf2/HO-1 Signaling Pathway Enhances Ability of Resveratrol to Inhibit UVB-induced Melanin

Abstract

Objective:This study was performed to investigate the relationship between the human melanogenesis and antioxidant systems and to further confirm the synergistic effect of oxyresveratrol (OXYR) and resveratrol (RES) in human epidermal melanocyte cell line.Methods:The human epidermal melanocyte line PIG1 cells were divided into the UV groups and control group, treated with different doses of UVB and without UVB, respectively. MTT assay and flow cytometry were used to detect cell viability and apoptosis. The expression of Nrf2/HO-1 and melanogenesis-associated proteins/genes was measured by Western blotting and real-time qPCR (RT-qPCR). pCMV6-XL5-Nrf2 was used to upregulate the expression of Nrf2. Subsequently, the proteins/genes levels of Nrf2/HO-1 and tyrosinase (TYR), melanin/eumelanin content, and reactive oxygen species (ROS) were analyzed. Isobologram analysis and cell experiment were used to analyze whether OXYR and RES inhibit TYR synergistically. Western blotting, RT-qPCR, and NaOH splitting method were used to determine the Nrf2/HO-1 and melanogenesis-associated proteins/genes expression and melanin content to evaluate the efficacy of OXYR and RES.Results:The activated Nrf2 and HO-1 eliminated ROS produced by UVB irradiation. The melanogenesis-associated proteins/genes of melanocyte-inducing transcription factor (MITF, P < 0.01 on protein expression), TYR (both P < 0.01), TYR-related protein (TRP)-1 (both P < 0.05), and TRP2 (P < 0.05 on mRNA expression) were activated in PIG1 cells by UVB irradiation. Simultaneously, the upregulation of Nrf2 significantly reduced melanogenesis formation (P < 0.001) and TYR level (P < 0.01 on protein expression). Moreover, OXYR and RES synergistically inhibited TYR activity (P < 0.001) and reduced melanin content (P < 0.001).Conclusions:A microbalance exists between Nrf2/HO-1 signaling and melanogenesis production in the UVB-induced responses of melanocytes. Simultaneously, OXYR enhances the ability of RES to inhibit melanin production.

Maclura cochinchinensis (Lour.) Corner Heartwood Extracts Containing Resveratrol and Oxyresveratrol Inhibit Melanogenesis in B16F10 Melanoma Cells

“…Oxyresveratrol is known to counteract melanogenesis induced by tyrosinase-related oxidative stress in B16F10 melanoma cells [ 33 ]. Furthermore, the activation of the Nrf2/HO-1 signaling pathway by oxyresveratrol significantly enhances the ability of resveratrol to suppress UVB-induced melanin production [ 41 ], whereas resveratrol impacts keratinocytes by modulating inflammatory responses, protecting the cells from oxidative damage, and facilitating the repair of the basement membrane [ 42 , 43 ]. The regulatory effects of resveratrol and oxyresveratrol on melanocyte activity are underscored by their antioxidant properties, which not only hold the potential to inhibit melanin production but also provide systemic advantages in managing melasma effectively.…”

Characterization, Stability, and Antibrowning Effects of Oxyresveratrol Cyclodextrin Complexes Combined Use of Hydroxypropyl Methylcellulose

“…It has also been proved that Oxy exhibited a good effect on inhibiting the browning of fresh-cut lotus slices [ 21 ], and the combination with VC improved the antibrowning effects on some fruits and vegetables greatly [ 56 , 57 ]. Oxy may have a synergistic effect with another antioxidant through a certain mechanism, that is, one antioxidant helps to regenerate the other [ 10 ]. In this study, fresh-cut apple slices were used as a model to re-evaluate the characteristics of Oxy–CDs in fresh-cut fruits, as well as the effects of adding HPMC and VC to the solution.…”

“…It is a 2′-hydroxylated derivative of resveratrol; however, it has less cytotoxicity, better solubility, higher cell permeability, and greater bioavailability than resveratrol [ 8 , 9 ]. Greater free-radical scavenging ability than ascorbic acid (VC) is found in Oxy, and there is much evidence to support the role of other antioxidants in synergistically enhancing the antioxidant effects of Oxy [ 10 , 11 ]. Therefore, Oxy is promising in functional food and medicine ingredients [ 12 ], especially to be used as an antibrowning additive to maintain the freshness of fruits and vegetables due to its powerful tyrosinase inhibitory effect [ 13 ].…”