Nur Dina Amalina, Sri Wahyuni, H. Harjito, Meiny Suzery, Bambang Cahyono
Aging is a medical problem affecting about 800 million people worldwide. However, the molecular mechanism of aging and aging-related disease has not yet been explored. Skin aging is a complex biological process primarily due to cellular senescence. Cellular senescence is an irreversible growth arrest that caused tissue to lose their cell-specific functionality, secreting pro-tumorigenic and pro-inflammatory cytokines, which eventually causes cancer. Citrus aurantium-derived secondary metabolites, including hesperidin, hesperetin, tangeretin, naringenin, nobiletin, and quercetin, are of vital importance to inhibiting aging due to their active properties. However, the effect of C. aurantium-derived secondary metabolites on the cells senescence and its molecular mechanism remains unclear. This study evaluated the inhibitory effect of C. aurantium peels extract (CAP) on Doxorubicin-stimulated cellular senescence. The anti-aging effect was observed using MTT assay continued by senescence-associated β-galactosidase (SA-βgal) activity detection test. CAP significantly decreased fibroblast cells (NIH3T3) with IC50 value of 303 µg/mL and suppressed up to 5.35% doxorubicin-induced cell senescence in doses-dependent manner. A bioinformatic approach was used to investigated the CAP molecular mechanism in senescence inhibition. Under the bioinformatics approach, we identified TP53, CCNA2, CDK1, CCNB1, MYC, CDC6, CDK2, EP300, CCND1, and AKT1 as potential targets of hesperidin, hesperetin, tangeretin, naringenin, nobiletin, and quercetin, a CAP secondary metabolite in cell senescence regulation. These findings suggest that CAP prevents aging process mainly inhibiting cellular senescence by targeting these genes. Further studies are needed to explore the full potential therapy of CAP in aging. © 2022, Faculty of Pharmaceutical Sciences, Chulalongkorn University. All rights reserved.
Pharmacy Study Program, Departement of Chemistry, Faculty of Mathematics and Natural Sciences, Semarang State University, Semarang, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Semarang State University, Semarang, Indonesia; Chemistry Department, Faculty of Scinces and Mathematics, Universitas Diponegoro, Semarang, Indonesia
