Atraric Acid Ameliorates Hyperpigmentation through the Downregulation of the PKA/CREB/MITF Signaling Pathway

Abstract

Atraric acid (AA) is derived from lichens and is widely used in perfumes for its desirable scent. It has been reported as having anti-inflammatory and antioxidant activity. Hyperpigmentation is the underlying cause of a variety of dermatological diseases that have a significant impact on patients’ quality of life and are frequently difficult to treat. This study aimed to explore the inhibitory effects of AA on hyperpigmentation in vitro and in vivo and its potential molecular mechanisms. The cytological results revealed that at a dose of 250 μM, AA may reduce melanin content and tyrosinase levels without causing cytotoxicity. Furthermore, the expression of melanocortin-1 receptor (MC1R), phosphorylated protein kinase A (pPKA) and phosphorylated cAMP response element binding protein (pCREB) were downregulated in AA-administrated cells. In vivo, histological analysis showed that AA could inhibit melanin production and tyrosinase activity, and 3% AA had the best activity, with almost no side effects. Furthermore, the results of Western blot analysis and RT-PCR suggested that AA may suppress the mRNA transcription of microphthalmia-associated transcription factor (MITF) protein and tyrosine protease by decreasing the expression of MC1R, consequently decreasing the phosphorylation of PKA and CREB. Finally, the MC1R inhibitor MSG606 verified the hypothesis that AA suppresses melanin formation by downregulating the PKA/CREB/MITF signaling pathway. Taken together, our study offers valuable information for the development of AA as a possible ingredient in skin-lightening cosmeceuticals and hyperpigmentation inhibitors.

Antioxidant and antidiabetic activity and phytoconstituents of lichen extracts with temperate and polar distribution

“…As for the DPPH analysis, the three extracts evidenced an IC 50 value much higher than the gallic acid standard, suggesting a medium-low inhibition capacity of the study concentrations used; however, the extract of O. frigida continued to show better antioxidant These results correlate positively with the reports of extracts and compounds isolated from other lichen species that show highly effective phenolic concentration and antioxidant activity through Frontiers in Pharmacology frontiersin.org colorimetric techniques (Luo et al, 2009;Mitrović et al, 2011;Jha et al, 2017;Studzińska-Sroka et al, 2021a;Elečko et al, 2022) and electrochemical, computational, and genetic studies (Kalra et al, 2023;Yañez et al, 2023). Likewise, the variability in the antioxidant properties of lichens is mediated by the geographical, altitudinal, and/or microhabitat conditions in which they develop working concentrations, metabolite isolation efficiency, types of solvent, and forms of extraction and exploration of the mechanisms of action (Ranković et al, 2012;White et al, 2014;Studzińska-Sroka et al, 2021b;Li et al, 2022;Popovici et al, 2022;Sánchez et al, 2022). On the other hand, the evident antioxidant capacity of lichenic species has supported their use for the evaluation of neuroprotective effects in in vitro and in vivo models, yielding positive results regarding cell viability, protection against induced oxidative stress, decrease in reactive oxygen species, improvement of mitochondrial function, and suppression of signaling pathways that induce inflammatory response in astrocytes (Fernández-Moriano et al, 2015;Fernández-Moriano et al, 2016;Lee et al, 2021;Ureña-Vacas et al, 2022b).…”