研究领域：药理学 皮肤科 生物化学 分子生物学

关键字：抗氧化肽 薛氏拟水龟 OS-LL11 紫外线照射 自由基 角质细胞 脂质过氧化 丙二醛 活性氧 过氧化氢酶 Keap-1 HO-1 GCLM NQO1 外用 超氧化物歧化酶 谷胱甘肽 一氧化氮 过氧化氢 IL-1α IL-1β IL-6 TNF-α 8-OHdG Bcl-2 Bax 凋亡小体 抗光损伤 药物 化妆品

鉴于紫外线照射对人类皮肤的不利影响，以及目前干预手段的局限性，发现具有抗光损伤活性的新分子仍至关重要。本研究从中国林蛙（Odorrana schmackeri）中分离获得一种新型生物活性肽（命名为OS-LL11，氨基酸序列为‘LLPPWLCPRNK’）。结果表明，OS-LL11可直接清除自由基，并通过降低脂质过氧化、丙二醛及活性氧水平，同时升高过氧化氢酶、Keap-1、血红素加氧酶-1（HO-1）、谷氨酸-半胱氨酸连接酶修饰亚基（GCLM）及NAD(P)H:醌氧化还原酶1（NQO1）水平，从而维持经紫外线B（UVB）或过氧化氢（H₂O₂）刺激的小鼠角质形成细胞活力。值得注意的是，OS-LL11外用给药可通过上调超氧化物歧化酶、谷胱甘肽及一氧化氮水平，同时下调H₂O₂、白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、8-羟基脱氧鸟苷（8-OHdG）、Bcl-2及Bax表达水平，以及减少凋亡小体数量，从而保护小鼠皮肤免受UVB照射损伤。本研究证实了一种新型两栖动物来源肽的抗光损伤活性，并揭示其潜在机制涉及自由基清除能力以及抗氧化、抗炎和抗凋亡作用。该研究为抗皮肤光损伤药物或化妆品的研发提供了新分子候选物，并凸显了两栖动物来源肽在光损伤皮肤干预中的应用前景。Given the adverse impact of ultraviolet irradiation on human skin, as well as currently limited interventions, the discovery of new molecules with anti-photodamage potency remains critical. In this research, we obtained a new bioactive peptide (named OS-LL11, amino acid sequence ‘LLPPWLCPRNK’) from Odorrana schmackeri . Results showed that OS-LL11 could directly scavenge free radicals and sustain the viability of mouse keratinocytes challenged by ultraviolet B (UVB) irradiation or hydrogen peroxide (H₂O₂ ) by decreasing the levels of lipid peroxidation , malondialdehyde , and reactive oxygen species while increasing the level of catalase , Keap-1, HO-1, GCLM , and NQO1. Interestingly, topical application of OS-LL11 protected mouse skin against UVB irradiation damage by up-regulating the levels of superoxide dismutase , glutathione , and nitric oxide , but down-regulating the levels of H₂O₂ , IL-1α, IL-1β, IL-6, TNF-α, 8-OHdG, Bcl-2, and Bax, as well as the number of apoptotic bodies. Our research demonstrated the anti-photodamage activity of a novel amphibian-derived peptide and the potential underlying mechanisms related to its free radical scavenging ability and antioxidant , anti-inflammatory, and anti-apoptotic activities. This study provides a new molecule for the development of anti-skin photodamage drugs or cosmetics and highlights the prospects of amphibian-derived peptides in photodamaged skin intervention.