Antioxidant and Photoprotective Capacity of Secondary Metabolites Isolated from Pseudocyphellaria berberina

<jats:p>Exposure to sunlight, whose main component is UV radiation (UVR), leads to various skin damage such as sunburns, premature aging, or more severe issues such as increased symptoms of autoimmune disease and skin cancer. Therefore, there is a growing interest in developing improved photoprotective agents that can protect skin from sunlight incidence and antioxidants that counteract the oxidative stress caused by it. Lichens are a source of such agents since they adapt to extreme environments including those with high UVR by biosynthesizing metabolites with those properties. In this study, brialmontin 2 (1), physciosporin (2), and pseudocyphellarin A (3) were isolated for the first time from the lichen Pseudocyphellaria berberina (G. Forst.) D. J. Galloway & P. James, along with calycin (4) and 22-hydroxystictan-3-one (5). Their structural characterization was carried out by spectroscopy (1H and 13C NMR). Sun protection factor (SPF) along with critical wavelength (λcrit), a UVA/UVB ratio (UVA/UVB-r) of one to five, and acetone extract (AE) were evaluated spectrophotometrically as a measure of their UVB and UVA photoprotective capacities, respectively. Additionally, their antioxidant activity was measured by scavenging DPPH free radicals (RSA). Compounds 2, 4, and AE showed “medium” UVB photoprotective capacities (with SPFs between 15 and 30). Additionally, 4 and AE presented “maximum” UVA photoprotective capacities (λcrit > 370 nm and UVA/UVB-r > 0.8), whereas this activity was “good” for 2 and 3 (λcrit 350 to 370 nm and UVA/UVB-r 0.4 to 0.6), and “moderate” for 1 (λcrit 335 to 350 nm and UVA/UVB-r 0.2 to 0.4). All compounds and AE showed antioxidant activity, standing out were AE and 4 with activity comparable to the controls (ca. 95 and 81 RSA %, respectively, at 1000 ppm). AE and 4 are dual agents with photoprotective (UVB-UVA) and antioxidant capacities that could help prevent skin damage associated with sunlight. In silico assays suggest that 4 spontaneously diffuses into the stratum corneum with limited absorption through the skin. Additionally, 4 lacks potential toxicity to Normal Human Epidermal Keratinocytes (showing viability ca. 70% at 100 ppm); therefore, it is a candidate for the development of sunscreen formulations.</jats:p>