Katrin Hollinger1, R Andrew Shanely2, John C Quindry3, Joshua T Selsby4. 1. Department of Animal Science, Iowa State University, Ames, IA 50011, USA. 2. Human Performance Laboratory, Appalachian State University, North Carolina Research Campus, Kannapolis, NC 28081, USA; Appalachian State University, College of Health Sciences, Boone, NC, USA. 3. School of Kinesiology, Auburn University, Auburn, AL 36849, USA. 4. Department of Animal Science, Iowa State University, Ames, IA 50011, USA. Electronic address: jselsby@iastate.edu.
Abstract
BACKGROUND & AIMS: Duchenne muscular dystrophy results from a mutation in the dystrophin gene, which leads to a dystrophin-deficiency. Dystrophic muscle is marked by progressive muscle injury and loss of muscle fibers. Activation of the PGC-1α pathway has been previously shown to decrease disease-related muscle damage. Oral administration of the flavonol, quercetin, appears to be an effective and safe method to activate the PGC-1α pathway. The aim of this investigation was to determine the extent to which long term dietary quercetin enrichment would decrease muscle injury in dystrophic skeletal muscle. We hypothesized that a quercetin enriched diet would rescue dystrophic muscle from further decline and increase utrophin abundance. METHODS: Beginning at three-months of age and continuing to nine-months of age mdx mice (n = 10/group) were assigned to either to mdx-control receiving standard chow or to mdx-quercetin receiving a 0.2% quercetin-enriched diet. At nine-months of age mice were sacrificed and costal diaphragms collected. One hemidiaphragm was used for histological analysis and the second hemidiaphragm was used to determine gene expression via RT-qPCR. RESULTS: The diaphragm from the mdx-quercetin group had 24% (p ≤ 0.05) more muscle fibers/area and 34% (p ≤ 0.05) fewer centrally nucleated fibers compared to the mdx-control group. Further, there were 44% (p ≤ 0.05) fewer infiltrating immune cells/area, a corresponding 31% (p ≤ 0.05) reduction in TNF gene expression, and a near 50% reduction in fibrosis. The quercetin-enriched diet increased expression of genes associated with oxidative metabolism but did not increase utrophin protein abundance. CONCLUSIONS: Long-term quercetin supplementation decreased disease-related muscle injury in dystrophic skeletal muscle; however the role of PGC-1α pathway activation as a mediator of this response is unclear.
BACKGROUND & AIMS:Duchenne muscular dystrophy results from a mutation in the dystrophin gene, which leads to a dystrophin-deficiency. Dystrophic muscle is marked by progressive muscle injury and loss of muscle fibers. Activation of the PGC-1α pathway has been previously shown to decrease disease-related muscle damage. Oral administration of the flavonol, quercetin, appears to be an effective and safe method to activate the PGC-1α pathway. The aim of this investigation was to determine the extent to which long term dietary quercetin enrichment would decrease muscle injury in dystrophic skeletal muscle. We hypothesized that a quercetin enriched diet would rescue dystrophic muscle from further decline and increase utrophin abundance. METHODS: Beginning at three-months of age and continuing to nine-months of age mdx mice (n = 10/group) were assigned to either to mdx-control receiving standard chow or to mdx-quercetin receiving a 0.2% quercetin-enriched diet. At nine-months of age mice were sacrificed and costal diaphragms collected. One hemidiaphragm was used for histological analysis and the second hemidiaphragm was used to determine gene expression via RT-qPCR. RESULTS: The diaphragm from the mdx-quercetin group had 24% (p ≤ 0.05) more muscle fibers/area and 34% (p ≤ 0.05) fewer centrally nucleated fibers compared to the mdx-control group. Further, there were 44% (p ≤ 0.05) fewer infiltrating immune cells/area, a corresponding 31% (p ≤ 0.05) reduction in TNF gene expression, and a near 50% reduction in fibrosis. The quercetin-enriched diet increased expression of genes associated with oxidative metabolism but did not increase utrophin protein abundance. CONCLUSIONS: Long-term quercetin supplementation decreased disease-related muscle injury in dystrophic skeletal muscle; however the role of PGC-1α pathway activation as a mediator of this response is unclear.
Authors: Joshua T Selsby; Christopher G Ballmann; Hannah R Spaulding; Jason W Ross; John C Quindry Journal: J Physiol Date: 2016-05-29 Impact factor: 5.182
Authors: Ipek Suntar; Antoni Sureda; Tarun Belwal; Ana Sanches Silva; Rosa Anna Vacca; Devesh Tewari; Eduardo Sobarzo-Sánchez; Seyed Fazel Nabavi; Samira Shirooie; Ahmad Reza Dehpour; Suowen Xu; Bahman Yousefi; Maryam Majidinia; Maria Daglia; Giuseppe D'Antona; Seyed Mohammad Nabavi Journal: Acta Pharm Sin B Date: 2020-01-08 Impact factor: 11.413