Piceatannol markedly upregulates heme oxygenase-1 expression and alleviates oxidative stress in skeletal muscle cells

Shiori Nonaka,Shinpei Kawakami,Hiroko Maruki-Uchida,Sadao Mori,Minoru Morita

doi:10.1016/j.bbrep.2019.100643

Abstract

Piceatannol (PIC), a phytochemical, is abundant in passion fruit (Passiflora edulis) seeds. In this study, we investigated the effects of PIC on the expression levels of antioxidant enzymes in C2C12 skeletal muscle cells and compared its effects with those of PIC analogues and polyphenols. We also evaluated its effects on hydrogen peroxide–induced accumulation of reactive oxygen species in C2C12 myotubes. Treatment with PIC led to dose-dependent upregulation of heme oxygenase-1 (Ho-1) and superoxide dismutase 1 (Sod1) mRNA expression in C2C12 myotubes. PIC was the most potent inducer of Ho-1 among the PIC analogues and major polyphenols tested. In addition, treatment with PIC suppressed the hydrogen peroxide–induced increase in intracellular reactive oxygen species levels. Our results suggest that PIC protects skeletal muscles from oxidative stress by activating antioxidant enzymes such as HO-1 and SOD1 and can therefore help prevent oxidative stress–induced muscle dysfunction such as muscle fatigue and sarcopenia.

Highlights

Reactive oxygen species (ROS) are generated by physical exercise and muscle contraction
To examine whether PIC affects the gene expression of antioxidant enzymes in skeletal muscle cells, heme oxygenase-1 (Ho-1) and superoxide dismutase 1 (Sod1) mRNA expression were analyzed by real-time PCR analysis
When C2C12 myotubes were treated with 10–50 μM PIC for 6 h, Ho-1 and Sod1 mRNA expression was upregulated in a dose-dependent manner (Fig. 1)

Summary

Introduction

Reactive oxygen species (ROS) are generated by physical exercise and muscle contraction. The Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2–related factor 2 (Nrf2) pathway regulates the gene expression of antioxidant enzymes such as heme oxygenase-1 (Ho-1) and superoxide dismutase 1 (Sod1); this signaling pathway preserves intracellular redox homeostasis [5]. ROS stimulates redox-sensitive signaling pathways, and activation of antioxidant enzymes prevents oxidative damage to tissues. Imbalances in normal redox states cause oxidative damage, and attenuation of antioxidant activity during aging is reported to contribute to the age-related loss of muscle [6]. Increasing the antioxidant capacity of skeletal muscles is one of the most valuable therapeutic approaches against for muscle dysfunction [7,8]

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Conclusion