Abstract

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function.

Highlights

  • The generation of reactive oxygen species (ROS), which are products of respiration, is believed to contribute substantially to aging [1, 2]

  • ATP production decreased in the Antimycin A (AMA) treated group, but increased by 50% in cells treated with flavonoids and extracts of S. baicalensis compared to AMA-treated group

  • L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression

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Summary

Introduction

The generation of ROS, which are products of respiration, is believed to contribute substantially to aging [1, 2]. Oxidative stress and mitochondrial dysfunction are important factors that contribute to aging [3]. The mitochondrial respiratory chain is a major site of ROS production in the cell. Generations of ROS play an important role in mitochondrial dysfunction and represent putative targets of antiaging strategies [5]. Antimycin A (AMA) damages mitochondria in many cell types by inhibiting mitochondrial electron transport [6, 7]. Complexes I and III of the mitochondrial electron transport chain are the major sites for ROS production. AMA binds to the Qi site of cytochrome c reductase, thereby the oxidation of ubiquinol in the electron transport chain of oxidative phosphorylation. AMA is known to cause the leakage of superoxide radicals from rat liver mitochondria [8]

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