A Novel Molecule 3-(1'-Methyltetrahydropyridinyl)-2,4-6-Trihydroxy Acetophenone Alleviates Ultraviolet-B-Induced Photoaging in Human Dermal Fibroblasts and BALB/c Mice

• Published in: Photochemistry and photobiology 2023-09, Vol.99 (5), p.1343-1351
• Main Authors: Naikoo, Shahid H, Rashid, Haroon, Gupta, Ragni, Sharma, Raghu Rai, Kumar, Sanjay, Ahmad, Riyaz, Gudup, Satish, Singh, Parvinder P, Abdullah, Sheikh Tasduq
• Format: Article
• Language: English
• Subjects: Acetophenone; Apoptosis; Collagen; Cosmeceuticals; Degradation; Dermis; Endoplasmic reticulum; Extracellular matrix; Fibroblasts; Homeostasis; MAP kinase; Matrix metalloproteinase; Matrix metalloproteinases; Membrane potential; Oxidation; Oxidative stress; Pharmacology; Phenotypes; Radiation damage; Radiation effects; Reactive oxygen species; Skin; Topical application; Ultraviolet radiation
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13784

Ultraviolet radiation (UVR) is the major exogenous agent that disturbs tissue homeostasis and hastens the onset of age-related phenotypes (photoaging). Exposure to UV-B radiation promotes apoptosis in human skin cells via induction of Reactive Oxygen Species (ROS)-mediated Endoplasmic Reticulum (ER) stress by activating the PERK-eIF2α-CHOP pathway, which plays a major role in exacerbating skin photoaging. Alleviating the production of ROS and boosting the antioxidant capacity of cells is the foremost therapeutic strategy to avert the repercussions of ultraviolet radiation exposure. In this study, we investigated the role of 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone (IIIM-8) in thwarting the UV-B-induced photoaging. We observed that IIIM-8 ameliorates UV-B-induced oxidative stress, ER stress, Loss of Mitochondrial membrane potential, MAPK activation and Inflammation in irradiated skin cells. Ultraviolet radiation-related damage to fibroblasts within the dermis leads to collagen degradation-the hallmark of photoaging. IIIM-8 substantially restored the synthesis of collagen and prevented its degradation via the downregulation of matrix metalloproteinases. Topical application of IIIM-8 prevented BALB/c mice skin from UV-B-induced leukocyte infiltration, epidermal thickening and disruption of Extracellular matrix components. Implying that IIIM-8 has a strong photoprotective property and has potential to be developed as a topical therapeutic/cosmeceutical agent against UV-B-induced photoaging.