Mycosporine-like amino acids (MAAs) are UVR-absorbing metabolites typically produced by cyanobacteria and marine algae, but their properties are not limited to direct sun screening protection. Herein, we examine the antioxidant activities of porphyra-334 and shinorine and demonstrate that these MAAs are prospective activators of the cytoprotective Keap1-Nrf2 pathway. The ability of porphyra-334 and shinorine to bind with Keap1 was determined using fluorescence polarization (FP) and thermal shift assays to detect Keap1 receptor antagonism. Concomitantly, the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. Surprisingly, enhanced transcriptional regulation was only promoted by MAAs in cells after exposure to UVR-induced oxidative stress. Furthermore, the in-vitro antioxidant activities of porphyra-334 and shinorine determined by the DPPH free-radical quenching assay were low in comparison to ascorbic acid. However, their antioxidant capacity determined by the ORAC assay to quench free radicals via hydrogen atom transfer is substantial. Hence, the dual nature of MAAs to provide antioxidant protection may offer a prospective chemotherapeutic strategy to prevent or retard the progression of multiple degenerative disorders of ageing.

中文翻译：

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类菌孢素氨基酸 porphyra-334 和 shinorine 是抗氧化剂和 Keap1-Nrf2 结合的直接拮抗剂。

类菌孢素氨基酸 (MAA) 是吸收紫外线的代谢物，通常由蓝细菌和海藻产生，但其特性不仅限于直接防晒保护。在此，我们检查了 porphyra-334 和 shinorine 的抗氧化活性，并证明这些 MAA 是细胞保护性 Keap1-Nrf2 途径的潜在激活剂。使用荧光偏振 (FP) 和热位移测定来检测 Keap1 受体拮抗作用，从而确定 porphyra-334 和 shinorine 与 Keap1 结合的能力。同时，通过测量 UVR 暴露前后原代皮肤成纤维细胞中编码氧化应激防御蛋白的 Nrf2 靶基因 mRNA 表达增加，也证实了 porphyra-334 和 shinorine 将 Nrf2 与 Keap1 解离的能力。令人惊讶的是，在暴露于 UVR 诱导的氧化应激后，只有 MAA 才能促进细胞中转录调控的增强。此外，通过 DPPH 自由基猝灭测定测定的 porphyra-334 和 shinorine 的体外抗氧化活性与抗坏血酸相比较低。然而，通过 ORAC 测定，它们通过氢原子转移消除自由基的抗氧化能力是巨大的。因此，MAA 提供抗氧化保护的双重性质可能提供一种前瞻性的化疗策略，以预防或延缓多种衰老退行性疾病的进展。