Rationally Designed Nonapeptides with Great Skin Photoprotective Effect through Producing Type 1 Collagen and Blocking the mTOR Pathway

• Published in: Journal of medicinal chemistry Vol. 66; no. 11; pp. 7615 - 7628
• Main Authors: Wang, Xu, Shi, Wenzhuang, Wang, Kang, Ye, Zifan, Wang, Runying, Wang, Hui, Yang, Huaixin, Xie, Zeping, Yu, Haining, Wang, Yipeng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08.06.2023
• Subjects: Animals; Collagen Type I - metabolism; Collagen Type I - pharmacology; Humans; Mice; Phosphatidylinositol 3-Kinases - metabolism; Signal Transduction; Skin - metabolism; Skin Aging; TOR Serine-Threonine Kinases - metabolism; Ultraviolet Rays - adverse effects
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.3c00503

Ultraviolet (UV), as the most common environmental stress factor to human skin, causes redox imbalance and leads to photoaging and the development of cancer. In this work, we screened a nonapeptide (PWH) with good activities of antioxidant, promoting the secretion of type 1 collagen (COL-1) and repairing damaged skin from a series of rationally designed novel short peptides. PWH could alleviate UV-A-induced oxidative stress, restrain pro-inflammatory cytokine production, protect mitochondrial function, and maintain autophagy activity. We also first indicated that inhibiting the PI3K/AKT/mTOR signaling pathway and restoration of autophagy activity might delay the photoaging process in skin cells. Topical applications of PWH were further demonstrated to exhibit significant protection in full-wavelength UV-induced skin aging in mice models both in the prophylaxis and treatment way. In addition, given the good stability and without unwanted toxicity and anaphylaxis, PWH could be a promising candidate for cosmetics and pharmaceuticals.