{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:17:45Z","timestamp":1782253065101,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["2019R1A5A2027340"],"award-info":[{"award-number":["2019R1A5A2027340"]}]},{"name":"National Research Foundation of Korea","award":["2021R1A2C2007937"],"award-info":[{"award-number":["2021R1A2C2007937"]}]},{"name":"National Research Foundation of Korea","award":["P0014630"],"award-info":[{"award-number":["P0014630"]}]},{"name":"Ministry of Trade, Industry, and Energy (MOTIE), Republic of Korea","award":["2019R1A5A2027340"],"award-info":[{"award-number":["2019R1A5A2027340"]}]},{"name":"Ministry of Trade, Industry, and Energy (MOTIE), Republic of Korea","award":["2021R1A2C2007937"],"award-info":[{"award-number":["2021R1A2C2007937"]}]},{"name":"Ministry of Trade, Industry, and Energy (MOTIE), Republic of Korea","award":["P0014630"],"award-info":[{"award-number":["P0014630"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-\u03b1, which is a major mediator of the aging process. In aged skin, TNF-\u03b1 provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-\u03b1 in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-\u03b1-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as \u2018ashwagandha\u2019, is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-\u03baB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.<\/jats:p>","DOI":"10.3390\/antiox11112248","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:31:27Z","timestamp":1668565887000},"page":"2248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-\u03b1 Stimulation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-2177","authenticated-orcid":false,"given":"Sullim","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Science, College of Bio-Nano Technology, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seulah","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oriental Medicine Biotechnology, College of Life Sciences, Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Republic of Korea"},{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Su","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Health Administration, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-9138","authenticated-orcid":false,"given":"Ki Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Woo, W.M. 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