Quercetin Prevents Unloading-Derived Disused Muscle Atrophy by Attenuating the Induction of Ubiquitin Ligases in Tail-Suspension Mice

Mukai, Rie; Nakao, Reiko; Yamamoto, Hironori; Nikawa, Takeshi; Takeda, Eiji; Terao, Junji

doi:10.1021/np100240y

Cited by 57 publications

(50 citation statements)

References 17 publications

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“…In recent years, the effects of flavonoids on muscle atrophy under various conditions have received increased attention. Quercetin has been shown to prevent obesity and disuse- induced muscle atrophy [49][50]. Baicalin and epigallocatechin-3-gallate were reported to attenuate skeletal muscle atrophy caused by cancer cachexia [51][52][53].…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Huang¹,

Chen²,

Ren³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Skeletal muscle atrophy is an important health issue and can impose tremendous economic burdens on healthcare systems. Glucocorticoids (GCs) are well-known factors that result in muscle atrophy observed in numerous pathological conditions. Therefore, the development of effective and safe therapeutic strategies for GC-induced muscle atrophy has significant clinical implications. Some natural compounds have been shown to effectively prevent muscle atrophy under several wasting conditions. Dihydromyricetin (DM), the most abundant flavonoid in Ampelopsis grossedentata, has a broad range of health benefits, but its effects on muscle atrophy are unclear. The purpose of this study was to evaluate the effects and underlying mechanisms of DM on muscle atrophy induced by the synthetic GC dexamethasone (Dex). Methods: The effects of DM on Dex-induced muscle atrophy were assessed in Sprague-Dawley rats and L6 myotubes. Muscle mass and myofiber cross-sectional areas were analyzed in gastrocnemius muscles. Muscle function was evaluated by a grip strength test. Myosin heavy chain (MHC) content and myotube diameter were measured in myotubes. Mitochondrial morphology was observed by transmission electron microscopy and confocal laser scanning microscopy. Mitochondrial DNA (mtDNA) was quantified by real-time PCR. Mitochondrial respiratory chain complex activities were examined using the MitoProfile Rapid Microplate Assay Kit, and mitochondrial membrane potential was assessed by JC-1 staining. Protein levels of mitochondrial biogenesis and dynamics markers were detected by western blotting. Myotubes were transfected with siRNAs targeting peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM) and mitofusin-2 (mfn2) to determine the underlying mechanisms. Results: In vivo, DM preserved muscles from weight and average fiber cross-sectional area losses and improved grip strength. In vitro, DM prevented the decrease in MHC content and myotube diameter. Moreover, DM stimulated mitochondrial biogenesis and promoted mitochondrial fusion, rescued the reduced mtDNA content, improved mitochondrial morphology, prevented the collapse in mitochondrial membrane potential and enhanced mitochondrial respiratory chain complex activities; these changes restored mitochondrial function and improved protein metabolism, contributing to the prevention of Dex-induced muscle atrophy. Furthermore, the protective effects of DM on mitochondrial function and muscle atrophy were alleviated by PGC-1α siRNA, TFAM siRNA and mfn2 siRNA transfection in vitro. Conclusion: DM attenuated Dex-induced muscle atrophy by reversing mitochondrial dysfunction, which was partially mediated by the PGC-1α/TFAM and PGC-1α/mfn2 signaling pathways. Our findings may open new avenues for identifying natural compounds that improve mitochondrial function as promising candidates for the management of muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Huang¹,

Chen²,

Ren³

et al. 2018

Cell Physiol Biochem

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“…Dietary flavonoids are ubiquitously included in plant foods and have attracted considerable attention regarding their health effects (11,12). Previously, periodic injection of the flavonol-type flavonoid quercetin into the gastrocnemius muscle was shown to be effective in preventing muscle weight loss in mice that underwent tail suspension (11).…”

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confidence: 99%

“…Previously, periodic injection of the flavonol-type flavonoid quercetin into the gastrocnemius muscle was shown to be effective in preventing muscle weight loss in mice that underwent tail suspension (11). Furthermore, the principal flavonoid prenylation enabled naringenin, which is commonly found in grapefruit and sour oranges, to prevent muscle atrophy induced by disuse in denervated mice (13).…”

mentioning

confidence: 99%

Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes

Shiota

Abe

Kawai

et al. 2015

J Nutr Sci Vitaminol

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Summary Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/ MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity. These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy.

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“…The bulk of previous studies of quercetin in rodent models examining motor performance have employed models of defects rather than treatment of normal animals. As examples, various forms of quercetin supplementation in mice have attenuated the defects in motor function and morphology following chronic tail suspension [9], or denervation or crush of the sciatic nerve [10]. Likewise, quercetin treatment in murine genetic models of muscle dysfunction accompanied by motor impairments has also been effective [30].…”

Section: Discussionmentioning

confidence: 99%

“…Related to possible anti-aging effects, effects of quercetin have been examined on muscle function and atrophy in various animal models. For example, Mukai et al [9] used a tail suspension model to induce muscle atrophy in mice and reported that quercetin treatment suppressed markers of oxidative stress and attenuated muscle weight loss. In a follow-up study, Mukai et al [10] evaluated the effects of quercetin in a mouse model of disuse muscle atrophy involving denervation of the sciatic nerve.…”

Section: Introductionmentioning

confidence: 99%

Quercetin Glycosides Improve Motor Performance and Muscle Weight in Adult Mice

Kanzaki¹,

Takemoto²,

Ono³

et al. 2019

J Nutr Food Sci

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Male C57BL/6J (B6) mice aged 24 weeks were provided two concentrations (1.5 or 3.0 g/L) of quercetin glycosides (QG) in drinking water over the subsequent 24 weeks. The objective was to determine if QG could improve motor function during early stages of aging. No sustained significant differences in body composition or food intake were noted to confirm the safety of QG treatment. Treated mice had significantly improved performance in grip strength and rotarod tests but not in treadmill performance. The functional benefits were reflected in muscle morphology with increased wet weights of a selected group of muscles (quadratus femoris, gastrocnemius, tibialis anterior, and soleus) in treated mice. Thus, it would appear that long-term oral treatment with QG can safely and effectively improve selected elements of motor performance and increase muscle mass during the early stages of aging.

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Quercetin Prevents Unloading-Derived Disused Muscle Atrophy by Attenuating the Induction of Ubiquitin Ligases in Tail-Suspension Mice

Cited by 57 publications

References 17 publications

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes

Quercetin Glycosides Improve Motor Performance and Muscle Weight in Adult Mice

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