Unripe Carica papaya Fresh Fruit Extract Protects against Methylglyoxal-Mediated Aging in Human Dermal Skin Fibroblasts

Abstract

The glycolytic metabolite methylglyoxal (MGO) initiates the formation of advanced glycation end products and oxidative stress leading to cellular senescence and skin aging. This study focuses on the anti-aging properties of unripe Carica papaya L. (UCP) fresh fruit extract on MGO-induced human dermal fibroblast senescence. We pretreated human foreskin fibroblasts with UCP before incubating them with MGO (400 ?M) for 72 h. We used the glycation inhibitor aminoguanidine hydrochloride (AG) as the positive control. Senescent fibroblasts were detected using senescence-associated beta-galactosidase activity and collagen type I expression (COL1A1). We investigated the changes in the Akt JNK/p38 mitogen-activated protein kinase (MAPK) c-Jun and nuclear factor kappa B (NF-kB) signaling pathways using Western blotting. UCP significantly suppressed MGO-induced senescent fibroblasts (from 20.90?2.00% to 11.78?2.04%) when compared with the baseline level at 7.10?0.90% (P<0.05). While COL1A1 was diminished by 43.35?1.56% (P<0.001) in the MGO-treated fibroblasts UCP and AG could recover COL1A1 to 63.22?4.78% and 64.39?3.34% respectively. MGO triggered overactivation of Akt JNK/p38 MAPK c-Jun and NF-kB by 2.10?0.09 8.10?0.37 6.60?0.29 2.18?0.23 and 3.74?0.37 folds respectively. UCP and AG significantly abolished these changes. Consistently MGO increased matrix metalloproteinase-1 (MMP-1) levels by 2.58?0.04 folds which was significantly suppressed by UCP and AG pretreatment to 1.87?0.11 and 1.69?0.07 folds respectively. In summary UCP controlled MGO-induced fibroblast senescence by suppressing the JNK/c-Jun/MMP and p38/NF-kB/COL1A1 pathways similar to the action of the glycation inhibitor AG. Therefore UCP can be considered a functional fruit for preventing and delaying skin aging. ? 2023 The Korean Society of Food Science and Nutrition.