Anti-Aging Activity Of Cucurbita moschata Ethanolic Extract Towards NIH3T3 Fibroblast Cells Induced By Doxorubicin

Abstract

Degenerative disease caused by decreasing organ function in old people has become the biggest death cause in the world. This aging process marked by senescence activity. An anti-aging agent from the medicinal plant has high potency to be developed, such as pumpkin seed (Cucurbita moschata) which contain tocopherol as antioxidant. The aim of this study is to investigate the anti-aging effect of pumpkin seed extract (PSE) on NIH 3T3 fibroblast normal cell induced by doxorubicin. This anti-aging effect was observed using MTT assay continued by SA- βgal (Senescence-Associated Beta-Galactosidase) activity detection test. The stability of molecular interaction between tocopherol and doxorubicin to CYP 3A4 as the oxidase enzyme was conducted using molecular docking. Based on in vitro test, PSE is not cytotoxic to NIH 3T3. PSE at the dose of 100,200,400, and 800 μg/mL decreased % cell senescence by 2,77; 4,5; 6; and 18 times respectively. Meanwhile, in silico test indicated that tocopherol (-107,409) has a higher interaction to CYP 3A4 compared to doxorubicin (-70,52). Both compounds have a similar binding site in Leu 364; Phe 435; Pro 434; Cys 442; Ile 369; Thr 309; dan Ala 305. The overall result of this study showed that PSE has anti-aging effect by decreasing SA- βgal activity. This anti-aging activity possibly due to the interaction between tocopherol to CYP 3A4 based on molecular docking.Keywords: anti-aging, Cucurbita moschata, tocopherol, SA-βgal, molecular docking