scholarly journals A Chalcone from Ashitaba (Angelica keiskei) Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2419 ◽  
Author(s):  
Minson Kweon ◽  
Hyejin Lee ◽  
Cheol Park ◽  
Yung Hyun Choi ◽  
Jae-Ha Ryu
Keyword(s):  
Muscle Atrophy ◽  
Muscle Protein ◽  
Ethanol Extract ◽  
Mitogen Activated Protein Kinase ◽  
Myoblast Differentiation ◽  
Active Principle ◽  
Mrna Levels ◽  
C2c12 Myoblasts ◽  
E3 Ligases ◽  
Angelica Keiskei

Ashitaba, Angelica keiskei Koidzumi (AK), as a traditional medicine in Korea, Japan, and China, has been known as an elixir of life having therapeutic potential. However, there is no scientific evidence to support that Ashitaba can enhance or maintain muscle strength. To find a new therapeutic agent from the medicinal plant, we evaluated the anti-myopathy effect of chalcones from ethanol extract of AK (EAK) in cellular and animal models of muscle atrophy. To examine anti-myopathy activity, EAK was treated into dexamethasone injected rats and muscle thickness and histopathological images were analyzed. Oral administration of EAK (250 or 500 mg/kg) alleviated muscle atrophic damages and down-regulated the mRNA levels of muscle-specific ubiquitin-E3 ligases. Among ten compounds isolated from EAK, 4-hydroxyderricin was the most effective principle in stimulating myogenesis of C2C12 myoblasts via activation of p38 mitogen-activated protein kinase (MAPK). In three cellular muscle atrophy models with C2C12 myoblasts damaged by dexamethasone or cancer cell-conditioned medium, 4-hydroxyderricin protected the myosin heavy chain (MHC) degradation through suppressing expressions of MAFbx, MuRF-1 and myostatin. These results suggest that the ethanol extract and its active principle, 4-hydroxyderricin from AK, can overcome the muscle atrophy through double mechanisms of decreasing muscle protein degradation and activating myoblast differentiation.

scholarly journals Time course expression of Foxo transcription factors in skeletal muscle following corticosteroid administration

2010 ◽  
Vol 108 (1) ◽  
pp. 137-145 ◽  
Author(s):  
John E. Cho ◽  
Mario Fournier ◽  
Xiaoyu Da ◽  
Michael I. Lewis
Keyword(s):  
Transcription Factors ◽  
Muscle Atrophy ◽  
Time Course ◽  
Muscle Protein ◽  
Mrna Levels ◽  
Limb Muscle ◽  
Corticosteroid Administration ◽  
E3 Ligases ◽  
Phosphorylated Akt ◽  
Foxo Transcription Factors

Increased expression of forkhead box O (Foxo) transcription factors were reported in cultured myotubes and mouse limb muscle with corticosteroid (CS) treatment. We previously reported that administration of CS to rats resulted in muscle fiber atrophy only by day 7. The aim of this study, therefore, was to evaluate the time-course changes in the expression of Foxo transcription factors and muscle-specific ubiquitin E3 ligases in rat limb muscle following CS administration. Triamcinolone (TRI; 1 mg · kg−1 · day−1 im) was administered for 1, 3, or 7 days. Control (CTL) rats were given saline. Muscle mRNA was analyzed by real-time RT-PCR. Compared with CTL, body weights of TRI-treated animals decreased by 3, 12, and 21% at days 1, 3, and 7, respectively. Muscle IGF-1 mRNA levels decreased by 33, 65, and 58% at days 1, 3, and 7 in TRI-treated rats compared with CTL. Levels of phosphorylated Akt were 28, 50, and 36% lower in TRI animals at these time points. Foxo1 mRNA increased progressively by 1.2-, 1.4-, and 2.5-fold at days 1, 3, and 7 in TRI animals. Similar changes were noted in the expression of Foxo3a mRNA (1.3-, 1.4-, and 2.6-fold increments). By contrast, Foxo4 mRNA was not significantly changed in TRI animals. With TRI, muscle atrophy F box/Atrogin-1 increased by 1.8-, 4.1-, and 7.5-fold at days 1, 3, and 7 compared with CTL rats. By contrast, muscle RING finger 1 increased only from day 7 (2.7-fold). Gradual reduction in IGF-I expression with TRI over the time series paralleled that of Akt. These findings are consistent with a progressive stimulus to muscle protein degradation and the need to process/remove disassembled muscle proteins via the ubiquitin-proteasome system. Elucidating the dynamic catabolic responses to CS challenge is important in understanding the mechanisms underlying muscle atrophy and therapeutic measures to offset this.

scholarly journals Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 2003 ◽  
Author(s):  
Ju-Hyoung Park ◽  
Min Hee Hwang ◽  
Young-Rak Cho ◽  
Seong Su Hong ◽  
Jae-Shin Kang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Ethanol Extract ◽  
Skin Lesions ◽  
Transepidermal Water Loss ◽  
Mapk Signaling ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Cytokines And Chemokines

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

scholarly journals Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2724 ◽  
Author(s):  
Hyejin Lee ◽  
Ji-Won Heo ◽  
A-Reum Kim ◽  
Minson Kweon ◽  
Sorim Nam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Inflammatory Responses ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Janus Kinase ◽  
Skeletal Muscle Atrophy ◽  
E3 Ligases

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world’s most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

scholarly journals Propolis Ethanol Extract Stimulates Cytokine and Chemokine Production through NF-κB Activation in C2C12 Myoblasts

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Kohei Washio ◽  
Mao Kobayashi ◽  
Natsuko Saito ◽  
Misato Amagasa ◽  
Hiroshi Kitamura
Keyword(s):  
Cytokine Production ◽  
Ethanol Extract ◽  
C2c12 Cells ◽  
Mrna Levels ◽  
Chemokine Production ◽  
C2c12 Myoblasts ◽  
Cytokines And Chemokines ◽  
Brazilian Propolis ◽  
Muscle Remodeling ◽  
Brazilian Green Propolis

Myoblast activation is a triggering event for muscle remodeling. We assessed the stimulatory effects of propolis, a beehive product, on myoblasts. After an 8 h treatment with 100 μg/mL of Brazilian propolis ethanol extract, expression of various chemokines, including CCL-2 and CCL-5, and cytokines, such as IL-6, increased. This propolis-induced cytokine production appears to depend on NF-κB activation, because the IKK inhibitor BMS-345541 repressed mRNA levels of CCL-2 by ~66%, CCL-5 by ~81%, and IL-6 by ~69% after propolis treatment. Supernatant from propolis-conditioned C2C12 cells upregulated RAW264 macrophage migration. The supernatant also stimulated RAW264 cells to produce angiogenic factors, including VEGF-A and MMP-12. Brazilian green propolis therefore causes myoblasts to secrete cytokines and chemokines, which might contribute to tissue remodeling of skeletal muscle.

scholarly journals Divergent Regulation of Myotube Formation and Gene Expression by E2 and EPA during In-Vitro Differentiation of C2C12 Myoblasts

2020 ◽  
Vol 21 (3) ◽  
pp. 745
Author(s):  
Orly Lacham-Kaplan ◽  
Donny M. Camera ◽  
John A. Hawley
Keyword(s):  
Synergistic Effect ◽  
Striated Muscle ◽  
Morphological Changes ◽  
Estrogen Receptor Α ◽  
Mitogen Activated Protein Kinase ◽  
Myoblast Differentiation ◽  
C2c12 Myoblasts ◽  
Myotube Formation

Estrogen (E2) and polyunsaturated fatty acids (n-3PUFA) supplements independently support general wellbeing and enhance muscle regeneration in-vivo and myotube formation in-vitro. However, the combined effect of E2 and n-3PUFA on myoblast differentiation is not known. The purpose of the study was to identify whether E2 and n-3PUFA possess a synergistic effect on in-vitro myogenesis. Mouse C2C12 myoblasts, a reliable model to reiterate myogenic events in-vitro, were treated with 10nM E2 and 50μM eicosapentaenoic acid (EPA) independently or combined, for 0–24 h or 0–120 h during differentiation. Immunofluorescence, targeted qPCR and next generation sequencing (NGS) were used to characterize morphological changes and differential expression of key genes involved in the regulation of myogenesis and muscle function pathways. E2 increased estrogen receptor α (Erα) and the expression of the mitogen-activated protein kinase 11 (Mapk11) within 1 h of treatment and improved myoblast differentiation and myotube formation. A significant reduction (p < 0.001) in myotube formation and in the expression of myogenic regulatory factors Mrfs (MyoD, Myog and Myh1) and the myoblast fusion related gene, Tmem8c, was observed in the presence of EPA and the combined E2/EPA treatment. Additionally, EPA treatment at 48 h of differentiation inhibited the majority of genes associated with the myogenic and striated muscle contraction pathways. In conclusion, EPA and E2 had no synergistic effect on myotube formation in-vitro. Independently, EPA inhibited myoblast differentiation and overrides the stimulatory effect of E2 when used in combination with E2.

scholarly journals Increase in p202 Expression during Skeletal Muscle Differentiation: Inhibition of MyoD Protein Expression and Activity by p202

1998 ◽  
Vol 18 (2) ◽  
pp. 1074-1083 ◽  
Author(s):  
Bansidhar Datta ◽  
Wang Min ◽  
Sandeep Burma ◽  
Peter Lengyel
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activity ◽  
Muscle Protein ◽  
Specific Binding ◽  
Muscle Differentiation ◽  
Myoblast Differentiation ◽  
Gene Overexpression ◽  
Skeletal Muscle Differentiation ◽  
C2c12 Myoblasts ◽  
Transfected Cells

ABSTRACT p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene expression by inhibiting the activity of various transcription factors including NF-κB, c-Fos, c-Jun, E2F-1, and p53. Here we report that p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differentiation of cultured C2C12 myoblasts to myotubes. When overexpressed in transfected myoblasts, p202 inhibited the expression of one muscle protein (MyoD) without affecting the expression of a second one (myogenin). Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an interaction of p202 with both proteins, as well as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibition of the expression of MyoD and of the transcriptional activity of MyoD and myogenin may account for the inhibition of the induction of myoblast differentiation by premature overexpression of p202.

scholarly journals Corylifol A from Psoralea corylifolia L. Enhances Myogenesis and Alleviates Muscle Atrophy

2020 ◽  
Vol 21 (5) ◽  
pp. 1571 ◽  
Author(s):  
Yeongeun Han ◽  
Hyejin Lee ◽  
Hua Li ◽  
Jae-Ha Ryu
Keyword(s):  
Muscle Atrophy ◽  
Skin Diseases ◽  
Mapk Signaling ◽  
Skeletal Muscle Atrophy ◽  
Myoblast Differentiation ◽  
Psoralea Corylifolia ◽  
E3 Ligases ◽  
Inflammatory Conditions ◽  
Skeletal Myoblasts ◽  
Myogenic Markers

Inflammatory conditions caused by cancer, chronic diseases or aging can lead to skeletal muscle atrophy. We identified myogenic compounds from Psoralea corylifolia (PC), a medicinal plant that has been used for the treatment of inflammatory and skin diseases. C2C12 mouse skeletal myoblasts were differentiated in the presence of eight compounds isolated from PC to evaluate their myogenic potential. Among them, corylifol A showed the strongest transactivation of MyoD and increased expression of myogenic markers, such as MyoD, myogenin and myosin heavy chain (MHC). Corylifol A increased the number of multinucleated and MHC-expressing myotubes. We also found that the p38 MAPK signaling pathway is essential for the myogenic action of corylifol A. Atrophic condition was induced by treatment with dexamethasone. Corylifol A protected against dexamethasone-induced myotube loss by increasing the proportion of multinucleated MHC-expressing myotubes compared with dexamethasone-damaged myotubes. Corylifol A reduced the expression of muscle-specific ubiquitin-E3 ligases (MAFbx and MuRF1) and myostatin, while activating Akt. These dual effects of corylifol A, inhibition of catabolic and activation of anabolic pathways, protect myotubes against dexamethasone damage. In summary, corylifol A isolated from P. corylifolia alleviates muscle atrophic condition through activating myoblast differentiation and suppressing muscle degradation in atrophic conditions.

scholarly journals Inula Japonica Thunb. Flower Ethanol Extract Improves Obesity and Exercise Endurance in Mice Fed A High-Fat Diet

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 17 ◽  
Author(s):  
So-Hyun Park ◽  
Da-Hye Lee ◽  
Min Jung Kim ◽  
Jiyun Ahn ◽  
Young-Jin Jang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Ethanol Extract ◽  
Flowering Plant ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Endurance Capacity ◽  
Protein Kinase Activity ◽  
Mrna Levels ◽  
High Fat

Inula japonica Thunb. (Asteraceae) is a flowering plant that grows mainly in Korea, Japan, and China and its flower extract has diverse biological effects such as anti-inflammatory and antioxidative activities. However, the effects on obesity and enhancement of endurance capacity have not been explored yet. This study aims to reveal the effects of I. japonica flower ethanol extract (IJE) on obesity and endurance capacity in high-fat diet (HFD) fed C57BL/6J mice and the mechanism. IJE inhibited lipid accumulation in 3T3-L1 adipocytes in vitro. Also, IJE-fed mice showed reduced body weight gain, hepatic lipid, and body fat mass, and increased muscle weight. IJE reduced lipid accumulation in the liver and adipose tissue by decreasing lipogenic and adipogenic gene expression. Additionally, consumption of low-dose IJE significantly enhanced endurance capacity via increasing AMP-activated protein kinase activity and mRNA levels of Myh7 and Myh2. Luteolin and 1β-hydroxyalantolactone (1β-HA), compounds of IJE, are involved in anti-adipogenesis in the 3T3-L cells and only luteolin increased the protein levels of MHC during C2C12 myoblast differentiation. Collectively, our results suggest that consumption of IJE not only helps to prevent obesity but also enhances endurance capacity reduced by HFD.

scholarly journals Identification of Withania somnifera-Silybum marianum-Trigonella foenum-graecum Formulation as a Nutritional Supplement to Contrast Muscle Atrophy and Sarcopenia

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Laura Salvadori ◽  
Manuela Mandrone ◽  
Tommaso Manenti ◽  
Catia Ercolani ◽  
Luca Cornioli ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Withania Somnifera ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Silybum Marianum ◽  
Trigonella Foenum Graecum ◽  
Age Related

Background: Muscle atrophy, i.e., the loss of skeletal muscle mass and function, is an unresolved problem associated with aging (sarcopenia) and several pathological conditions. The imbalance between myofibrillary protein breakdown (especially the adult isoforms of myosin heavy chain, MyHC) and synthesis, and the reduction of muscle regenerative potential are main causes of muscle atrophy. Methods: Starting from one-hundred dried hydroalcoholic extracts of medical plants, we identified those able to contrast the reduction of C2C12 myotube diameter in well-characterized in vitro models mimicking muscle atrophy associated to inflammatory states, glucocorticoid treatment or nutrient deprivation. Based on their ability to rescue type II MyHC (MyHC-II) expression in atrophying conditions, six extracts with different phytochemical profiles were selected, mixed in groups of three, and tested on atrophic myotubes. The molecular mechanism underpinning the effects of the most efficacious formulation, and its efficacy on myotubes obtained from muscle biopsies of young and sarcopenic subjects were also investigated. Results: We identified WST (Withania somnifera, Silybum marianum, Trigonella foenum-graecum) formulation as extremely efficacious in protecting C2C12 myotubes against MyHC-II degradation by stimulating Akt (protein kinase B)-dependent protein synthesis and p38 MAPK (p38 mitogen-activated protein kinase)/myogenin-dependent myoblast differentiation. WST sustains trophism in C2C12 and young myotubes, and rescues the size, developmental MyHC expression and myoblast fusion in sarcopenic myotubes. Conclusion: WST strongly counteracts muscle atrophy associated to different conditions in vitro. The future validation in vivo of our results might lead to the use of WST as a food supplement to sustain muscle mass in diffuse atrophying conditions, and to reverse the age-related functional decline of human muscles, thus improving people quality of life and reducing social and health-care costs.

PGC-1α is associated with C2C12 Myoblast differentiation

2014 ◽  
Vol 9 (11) ◽  
pp. 1030-1036 ◽  
Author(s):  
Yaqiu Lin ◽  
Yanying Zhao ◽  
Ruiwen Li ◽  
Jiaqi Gong ◽  
Yucai Zheng ◽  
...  
Keyword(s):  
Mrna Level ◽  
Biological Significance ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Mrna Levels ◽  
Transfected Cells ◽  
Myosin Heavy Chain Isoform ◽  
Important Mediator

AbstractPGC-1α has been implicated as an important mediator of functional capacity of skeletal muscle. However, the role of PGC-1α in myoblast differentiation remains unexplored. In the present study, we observed a significant up-regulation of PGC-1α expression during the differentiation of murine C2C12 myoblast. To understand the biological significance of PGC-1α up-regulation in myoblast differentiation, C2C12 cells were transfected with murine PGC-1α cDNA and siRNA targeting PGC-1α, respectively. PGC-1α over-expressing clones fused to form typical myotubes with higher mRNA level of myosin heavy chain isoform I (MyHCI) and lower MyHCIIX. No obvious differentiation was observed in PGC-1α-targeted siRNA-transfected cells with marked decrement of mRNA levels of MyHCI and MyHCIIX. Furthermore, PGC-1α increased the expression of MyoD and MyoG in C2C12 cells, which controlled the commitment of precursor cells to myotubes. These results indicate that PGC-1α is associated with myoblast differentiation and elevates MyoD and MyoG expression levels in C2C12 cells.

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