Myricetin improves endurance capacity and mitochondrial density by activating SIRT1 and PGC-1α

Jung, Hoe‐Yune; Lee, Dong-Yeop; Ryu, Hye Guk; Choi, Bo Hwa; Go, Younghoon; Lee, Namgyu; Lee, Dohyun; Son, Heehwa G.; Jeon, Jongsu; Kim, Seong Hoon; Yoon, Jong Hyuk; Park, Seon Min; Lee, Seung-Jae; Lee, In Kyu; Choi, Kwan Yong; Ryu, Sung Ho; Nohara, Kazunari; Yoo, Seung Hee; Chen, Jake Y.; Kim, Kyong‐Tai

doi:10.1038/s41598-017-05303-2

Cited by 52 publications

(29 citation statements)

References 46 publications

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“…Quercetin prevents muscle atrophy by targeting mitochondria in denervated mice model . Myricetin enhances mitochondrial activity by activating PGC‐1α and SIRT1, to improve physical endurance in mice . Dihydromyricetin, a dihydroflavonol isolated from Chinese bayberry, has a wide variety of bioactivities, including anti‐inflammatory, antioxidative, and anti‐tumorigenic effects.…”

Section: Introductionmentioning

confidence: 99%

“…20 Myricetin enhances mitochondrial activity by activating PGC-1α and SIRT1, to improve physical endurance in mice. 21 Dihydromyricetin, a dihydroflavonol isolated from Chinese bayberry, has a wide variety of bioactivities, including anti-inflammatory, antioxidative, and anti-tumorigenic effects. A recent study showed dihydromyricetin ameliorates D-galactose-induced atrophy of skeletal muscle through AMP-activated protein kinase (AMPK)/SIRT1/PGC-1α signalling cascade.…”

Section: Introductionmentioning

confidence: 99%

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Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

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Background Muscle atrophy and weakness are adverse effects of high dose or the sustained usage of glucocorticoids. Loss of mitochondria and degradation of protein are highly correlated with muscle dysfunction. The deacetylase sirtuin 1 (SIRT1) plays a vital role in muscle remodelling. The current study was designed to identify myricanol as a SIRT1 activator, which could protect skeletal muscle against dexamethasone‐induced wasting. Methods The dexamethasone‐induced atrophy in C2C12 myotubes was evaluated by expression of myosin heavy chain, muscle atrophy F‐box (atrogin‐1), and muscle ring finger 1 (MuRF1), using western blots. The mitochondrial content and oxygen consumption were assessed by MitoTracker staining and extracellular flux analysis, respectively. Muscle dysfunction was established in male C57BL/6 mice (8–10 weeks old, n = 6) treated with a relatively high dose of dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, forced swimming capacity, muscle weight, and muscle histology were assessed. The expression of proteolysis‐related, autophagy‐related, apoptosis‐related, and mitochondria‐related proteins was analysed by western blots or immunoprecipitation. Results Myricanol (10 μM) was found to rescue dexamethasone‐induced muscle atrophy and dysfunction in C2C12 myotubes, indicated by increased expression of myosin heavy chain (0.33 ± 0.14 vs. 0.89 ± 0.21, * P < 0.05), decreased expression of atrogin‐1 (2.31 ± 0.67 vs. 1.53 ± 0.25, * P < 0.05) and MuRF1 (1.55 ± 0.08 vs. 0.99 ± 0.12, ** P < 0.01), and elevated ATP production (3.83 ± 0.46 vs. 5.84 ± 0.79 nM/mg protein, ** P < 0.01), mitochondrial content (68.12 ± 10.07% vs. 116.38 ± 5.12%, * P < 0.05), and mitochondrial oxygen consumption (166.59 ± 22.89 vs. 223.77 ± 22.59 pmol/min, ** P < 0.01). Myricanol directly binds and activates SIRT1, with binding energy of −5.87 kcal/mol. Through activating SIRT1 deacetylation, myricanol inhibits forkhead box O 3a transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, and increases peroxisome proliferator‐activated receptor γ coactivator‐1α activity to promote mitochondrial biogenesis. In dexamethasone‐induced muscle wasting C57BL/6 mice, 5 mg/kg myricanol treatment reduces the loss of muscle mass; the percentages of quadriceps and gastrocnemius muscle in myricanol‐treated mice are 1.36 ± 0.02% and 0.87 ± 0.08%, respectively (cf. 1.18 ± 0.06% and 0.78 ± 0.05% in dexamethasone‐treated mice, respectively). Myricanol also rescues dexamethasone‐induced muscle weakness, indicated by improved grip strength (70.90 ± 4.59 vs. 120.58 ± 7.93 g, ** P < 0.01) and prolonged swimming exhaustive time (48.80 ± 11.43 vs. 83.75 ± 15.19 s, **...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

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“…For cells experiment, a stock myricetin solution (10 mM) was prepared using DMSO as the solvent and stored at −20 until use. Myricetin concentration for cells treatment was based on our primary study and previous in vitro bioactivity work (29,40,41).…”

Section: Animals and Experimental Protocolsmentioning

confidence: 99%

Myricetin Modulates Macrophage Polarization and Mitigates Liver Inflammation and Fibrosis in a Murine Model of Nonalcoholic Steatohepatitis

Yao

et al. 2020

Front. Med.

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This study aimed to investigate the beneficial effects of myricetin in a diet-induced nonalcoholic steatohepatitis (NASH) model and the underlying mechanism. C57BL/6J mice were fed a standard chow or the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 8 weeks with the treatment of myricetin (100 mg/kg) or vehicle by daily gavage. Hepatic inflammation, steatosis, fibrosis, and hepatic stellate cells (HSC) activation were assessed. We also analyzed M1 and M2 macrophages and its related markers in livers from NASH mice and in RAW264.7 macrophages stimulated by lipopolysaccharide (LPS) or interleukin 4 (IL-4) in vitro. Furthermore, we determined the effect of myricetin on the triggering receptor expressed on myeloid cells-1 (TREM-1), toll like receptor (TLR) 2 and 4, and myeloid differentiation factor 88 (MyD88) signaling both in livers from mice and in RAW264.7 cells stimulated by LPS. Our results revealed that myricetin remarkably ameliorated hepatic steatosis, inflammation, and inhibited hepatic macrophage infiltration in CDAHFD-fed mice. Myricetin-treated to CDAHFD-fed mice also inhibited liver fibrosis and HSC activation when compared with vehicle-treated to those mice. Moreover, myricetin inhibited M1 macrophage polarization and its relative markers in livers of NASH mice while induced M2 polarization. Similarly, in vitro study, myricetin inhibited the LPS-induced mRNA expression of M1 macrophages marker genes and induced IL-4-induced M2 macrophage marker genes in RAW264.7 macrophages. Mechanically, myricetin inhibited the expression of TREM-1 and TLR2/4-MyD88 signaling molecules in livers from NASH mice and in RAW264.7 macrophages stimulated by LPS in vitro. Additionally, myricetin inhibited the activation of nuclear factor (NF)-κB signaling and the phosphorylation of the signal transducer and activation of transcription 3 (STAT3) in LPS-stimulated RAW264.7 macrophages. Taken together, our data indicated that myricetin modulated the polarization of macrophages via inhibiting the TREM-1-TLR2/4-MyD88 signaling molecules in macrophages and therefore mitigated NASH and hepatic fibrosis in the CDAHFD-diet-induced NASH model in mice.

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“…Yellow pigments, monascin, and ankaflavin, as secondary metabolites derived from monascus-fermented products, could reduce fatty acid accumulation partly mediated by the AMPK signaling activation and enhancement of b-oxidation by PGC-1a (Hsu et al, 2014). Myricetin, a natural flavonol with many biological activities, decreased PGC-1a acetylation through SIRT1 activation, and thus enhanced mitochondrial activity, suggesting its potential role in regulating hepatic lipid metabolism (Jung et al, 2017).…”

Section: Hepg2mentioning

confidence: 99%

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism

Guo

et al. 2020

Front. Pharmacol.

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The dysregulation of hepatic lipid metabolism is one of the hallmarks in many liver diseases including alcoholic liver diseases (ALD) and non-alcoholic fatty liver diseases (NAFLD). Hepatic inflammation, lipoperoxidative stress as well as the imbalance between lipid availability and lipid disposal, are direct causes of liver steatosis. The application of herbal medicines with anti-oxidative stress and lipid-balancing properties has been extensively attempted as pharmaceutical intervention for liver disorders in experimental and clinical studies. Although the molecular mechanisms underlying their hepatoprotective effects warrant further exploration, increasing evidence demonstrated that many herbal medicines are involved in regulating lipid accumulation processes including hepatic lipolytic and lipogenic pathways, such as mitochondrial and peroxisomal b-oxidation, the secretion of very low density lipoprotein (VLDL), the non-esterified fatty acid (NEFA) uptake, and some vital hepatic lipogenic enzymes. Therefore, in this review, the pathways or crucial mediators participated in the dysregulation of hepatic lipid metabolism are systematically summarized, followed by the current evidences and advances in the positive impacts of herbal medicines and natural products on the lipid metabolism pathways are detailed. Furthermore, several herbal formulas, herbs or herbal derivatives, such as Erchen Dection, Danshen, resveratrol, and berberine, which have been extensively studied for their promising potential in mediating lipid metabolism, are particularly highlighted in this review. FIGURE 1 | Major processes involved in hepatic lipid metabolism. Li et al.

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Myricetin improves endurance capacity and mitochondrial density by activating SIRT1 and PGC-1α

Cited by 52 publications

References 46 publications

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Myricetin Modulates Macrophage Polarization and Mitigates Liver Inflammation and Fibrosis in a Murine Model of Nonalcoholic Steatohepatitis

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism

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