Thai herbal antipyretic 22 formula (APF22) inhibits UVA‐mediated melanogenesis through activation of Nrf2‐regulated antioxidant defense

Abstract

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA-irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2-antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione-S-transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA-mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.

The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense

“…The HRF extracts and HSP also enhanced a substantial Nrf2 activation in mouse skin, together with the upregulation of antioxidant defense enzymes GST and NQO-1. We and other studies have reported that activation of Nrf2 is involved in the mechanisms underlying the photoprotective effect of phytochemicals and botanical extracts against UVR-induced damage of the skin cells including melanocytes and keratinocytes (Chaiprasongsuk et al, 2016;Chaiprasongsuk et al, 2017;Onkoksoong et al, 2018). Our findings strongly suggested that the photoprotective actions of HRF extracts and HSP at concentrations of 30 μg/ml and 10 μg/ml, protected against UVA-induced photoaging of NHDFs.…”

“…generated during UVA exposure of the skin causes upregulation of MMPs, in particular MMP-1, responsible for the degradation of the ECM proteins including collagen that contributes to photoaging (Pittayapruek et al, 2016). We previously reported that the Thai Herbal HRF extracts protected against UVA-induced MMP-1 in keratinocyte HaCaT cells (Pluemsamran et al, 2013) and melanogenesis in B16F10 melanoma cells through activating Nrf2-dependent antioxidant defenses (Onkoksoong et al, 2018). In this study, we determined the anti-photoaging effects of HRF extract and its possible active ingredient, hesperetin (HSP), on normal human dermal fibroblasts in vitro and on mouse skin in vivo exposed to UVA in association with modulation of Nrf2-related antioxidant signaling.…”

“…As demonstrated by the chemical profiling of HRF and all five components (the roots of five plants used in preparation of the HRF) using the liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), hesperetin (HSP) (or the (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one) was also suggested as a putative bioactive constituent of the HRF (Suebnooch et al, 2018). We and others have reported the beneficial roles of the HRF and their components in protecting against skin disorders possibly due to several pharmacological actions in vitro and in vivo including antiacne (Jantarat et al, 2018), anti-allergic (Juckmeta et al, 2014), anti-inflammatory (Juckmeta et al, 2019), antioxidant and anticollagenase (Pluemsamran et al, 2013), depigmenting (Onkoksoong et al, 2018), and wound healing properties (Mehtaa et al, 2012).…”

Oxidative stress and antioxidants in the pathophysiology of malignant melanoma

“…This compound suppressed these cells both in vitro as well as in xenografts in mice. -Using an herbal antipyrelic formula UVA-A mediated melanogenesis was inhibited through the activation of Nrf2 regulated antioxidant defenses (Onkoksoong et al, 2018). -A recent broad-based mechanistic study of inhibitors of cytosolic thioredoxin reductase 1 in many tumor types produced impaired growth of syngeneic mouse tumors and viability of human tumors xenografts with little mitochondrial toxicity (Stafford et al, 2018).…”

Effect of Sucrier Banana Peel Extracts on Inhibition of Melanogenesis through the ERK Signaling Pathway

“…Regulation of MITF starts from signal transduction after α-MSH bind to MC1R receptor which stimulates mitogen-activated protein kinase (MARKs) which is serine/threonine kinase and also include extracellular signaling-regulated kinase (ERK) and also p38 as well. Several studies found that melanin synthesis is controlled by several signaling pathways such as phosphotidylineasital-3-kinase (PI3K/AKT) can be suppressed by natural substances which contain polyphenol group through ERK signaling pathway of B16F10 mouse melanoma cells 5,6.…”