# Microwave-Assisted Propolis Extract Attenuates Oxidative-Stress- and Replicative Senescence via NRF2 and Wnt/β-Catenin–TERT Activation in Human Dermal Fibroblasts

## TL;DR

A microwave-assisted propolis extract reduces skin aging by targeting oxidative stress and cellular senescence in human skin cells.

## Contribution

MAPE shows novel anti-aging effects via NRF2 and Wnt/β-catenin–TERT pathways in dermal fibroblasts.

## Key findings

- MAPE reduces ROS and activates NRF2-dependent antioxidant pathways in fibroblasts.
- MAPE suppresses senescence markers and improves extracellular matrix homeostasis.
- MAPE modulates Wnt/β-catenin signaling and increases TERT expression, similar to a known Wnt activator.

## Abstract

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H2O2-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging.