Nuciferine Attenuates Cigarette Smoke-Induced Senescence in HepG-2 Cells via the miR-217/SIRT1/Nrf2 Pathway

Abstract

The lotus leaf, widely used in both medicine and cuisine, contains bioactive compounds with therapeutic potential. Nuciferine (NF), an active constituent of significant importance, is extracted from the lotus leaf. The present study sought to uncover the molecular pathways through which Nuciferine (NF) mitigates cellular senescence triggered by Cigarette Smoke Components (CSCs) in HepG-2 cells, employing an experimental model where NF was administered to CSC-induced HepG-2 cells.Reverse transcription polymerase chain reaction (RT-PCR) was employed to assess the expression of aging-related genes within HepG-2 cells The expression profiles of endogenous miRNAs were analyzed, while the regulatory relationship between miR-217-5p and SIRT1 was examined through Dual Luciferase Reporter Gene Assay (DLRG). Nuciferine treatment significantly increased antioxidant enzyme levels (SOD and GSH-Px) while reducing malondialdehyde (MDA) levels compared to CSC-treated cells (P<0.05). Additionally, SIRT1, Nrf2, and FOXO1 expression levels were significantly upregulated in the NF-treated group (P<0.05). The targeting association between miR-217-5p and SIRT1 mRNA was further substantiated using the DLRG approach. Mechanistic investigations revealed that NF counteracts CSC-triggered senescence in HepG-2 cells through miR-217-5p-mediated regulation of its downstream targets, leading to subsequent activation of the SIRT1/Nrf2 cascade. These findings position Nuciferine as a promising dietary compound with potential anti-aging properties.