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Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes.

ABSTRACT: Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1-10 ?g/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 ?g/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged with sarcopenia and the patients with disuse atrophy.

SUBMITTER: Kim CH

PROVIDER: S-EPMC4898430 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes.

Kim Cy Hyun CH Shin Jin-Hong JH Hwang Sung Jun SJ Choi Yung Hyun YH Kim Dae-Seong DS Kim Cheol Min CM

International journal of nanomedicine 20160531

Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1-10 μg/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 μg/mL of SF extract, enhancing differentiation up to 1.4-fold ...[more]

PMID: 27330287

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Project description:This study attempted to filter active components with antioxidant activities based on the differing antioxidant abilities of Schisandrae Sphenantherae Fructus (SSF) and Schisandrae Chinensis Fructus (SCF). First, the antioxidant activity of SSF and SCF was evaluated through the DPPH free radical scavenging method and compared with the half maximal inhibitory concentration (IC50) value. Next, components of SSF and SCF were detected by employing ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UPLC-QEO/MS) technology, and differential compounds were screened out as potential antioxidant compounds by using Compound Discover 3.1 Software. After that step, in order to verify the antioxidant compounds, the network method was applied. Biological targets were searched in the GeneCards database, and that related to antioxidant ability were selected in the Comparative Toxicogenomics Database (CTD). Finally, the pharmacology network was constructed. Results showed that SSF and SCF possessed different compounds and antioxidant abilities. A total of 14 differential compounds such as γ-schizandrin, schisandrin B, schisandrin, and tigloylgomisin H between them were screened out and identified. Twenty targets associated with antioxidant activity contained MAP2K1, MAPK8, RPS6KB1, PRKCB, HIF1A, and so on were investigated. Thirty-six pathways contained HIF-1 signaling pathways, choline metabolism in cancer, serotonergic synapse, Fc epsilon RI signaling pathway, GnRH signaling pathway, and so on related to the above twenty targets were identified. The pharmacology network analysis indicated that the differential components may be helpful in treating various diseases, especially cancer, by exerting antioxidant activity. In conclusion, this study provided a novel method for identifying active components with antioxidant activity in SSF and SCF, and this method may be applicable for the filtration of bioactive components in other herbs.

Project description:Objective: Schisandrae Sphenantherae Fructus (SSF) is a traditional Chinese medicine used to treat coughs and pulmonary inflammatory diseases. However, the pharmacodynamic material basis and mechanisms for SSF in asthma treatment remain unclear. This study aims to screen the anti-asthmatic fraction and verify the pharmacodynamic material basis, predict the potential mechanism, and verify the interaction ability between compounds and core targets. Methods: First, three fractions from SSF were compared in terms of composition, comparison, and anti-asthmatic effects. Then, the ultra-performance liquid chromatography-quadrupole/time-of-flight-mass spectrometry/mass spectrometry (UPLC-Q/TOF-MS/MS) strategy was used to identify the compounds from the active fraction, and the anti-asthmatic efficacy of the active fraction was further studied by the ovalbumin (OVA)-induced asthma murine model. Finally, network pharmacology and molecular methods were used to study the relationships between active compounds, core targets, and key pathways of PEF in asthma treatments. Results: The petroleum ether fraction (PEF) of SSF showed better effects and could significantly diminish lung inflammation and mitigate the level of serum immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL-6, IL-13, and IL-17 in mice. A total of 26 compounds from the PEF were identified, among which the main compounds are lignans and triterpenes. Moreover, 21 active compounds, 129 overlap-ping targets, and 10 pathways were screened by network pharmacology tools. The top five core targets may play a great role in asthma treatment. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the PEF can treat asthma by acting on multiple asthma pathological processes, including the IL-17 signaling pathway, T helper (Th) 17 cell differentiation, and the calcium signaling pathway. Molecular docking was performed to evaluate the interactions of the protein-ligand binding, and most docked complexes had a good binding ability. Conclusion: The present results might contribute to exploring the active compounds with anti-asthmatic activity.

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Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes.

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Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes.

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