Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel block...

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Main Authors: Sinenhlanhla X. H. Mthembu, Christo J. F. Muller, Phiwayinkosi V. Dludla, Evelyn Madoroba, Abidemi P. Kappo, Sithandiwe E. Mazibuko-Mbeje
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/20/6289
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author Sinenhlanhla X. H. Mthembu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Evelyn Madoroba
Abidemi P. Kappo
Sithandiwe E. Mazibuko-Mbeje
author_facet Sinenhlanhla X. H. Mthembu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Evelyn Madoroba
Abidemi P. Kappo
Sithandiwe E. Mazibuko-Mbeje
author_sort Sinenhlanhla X. H. Mthembu
collection DOAJ
description The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as <i>Ucp 2</i>, <i>Complex 1/3</i>, <i>Sirt 1</i>, <i>Nrf 1</i>, and <i>Tfam</i>. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.
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spelling doaj.art-81b149a68e934cd49469547e609c477e2023-11-22T19:21:02ZengMDPI AGMolecules1420-30492021-10-012620628910.3390/molecules26206289Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle CellsSinenhlanhla X. H. Mthembu0Christo J. F. Muller1Phiwayinkosi V. Dludla2Evelyn Madoroba3Abidemi P. Kappo4Sithandiwe E. Mazibuko-Mbeje5Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7505, South AfricaDepartment of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South AfricaDepartment of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, Johannesburg 2006, South AfricaDepartment of Biochemistry, Faculty of Natural and Agricultural Sciences, Mafikeng Campus, North West University, Private Bag X 2046, Mmabatho 2735, South AfricaThe current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as <i>Ucp 2</i>, <i>Complex 1/3</i>, <i>Sirt 1</i>, <i>Nrf 1</i>, and <i>Tfam</i>. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.https://www.mdpi.com/1420-3049/26/20/6289antimycin Amitochondrial dysfunctionskeletal muscleisoorientinorientinaspalathin
spellingShingle Sinenhlanhla X. H. Mthembu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Evelyn Madoroba
Abidemi P. Kappo
Sithandiwe E. Mazibuko-Mbeje
Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
Molecules
antimycin A
mitochondrial dysfunction
skeletal muscle
isoorientin
orientin
aspalathin
title Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
title_full Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
title_fullStr Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
title_full_unstemmed Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
title_short Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
title_sort rooibos flavonoids aspalathin isoorientin and orientin ameliorate antimycin a induced mitochondrial dysfunction by improving mitochondrial bioenergetics in cultured skeletal muscle cells
topic antimycin A
mitochondrial dysfunction
skeletal muscle
isoorientin
orientin
aspalathin
url https://www.mdpi.com/1420-3049/26/20/6289
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