Effect of Ashwagandha Withanolides on Muscle Cell Differentiation

Withania somnifera (Ashwagandha) is used in Indian traditional medicine, Ayurveda, and is believed to have a variety of health-promoting effects. The molecular mechanisms and pathways underlying these effects have not yet been sufficiently explored. In this study, we investigated the effect of Ashwagandha extracts and their major withanolides (withaferin A and withanone) on muscle cell differentiation using C2C12 myoblasts. We found that withaferin A and withanone and Ashwagandha extracts possessing different ratios of these active ingredients have different effects on the differentiation of C2C12. Withanone and withanone-rich extracts caused stronger differentiation of myoblasts to myotubes, deaggregation of heat- and metal-stress-induced aggregated proteins, and activation of hypoxia and autophagy pathways. Of note, the Parkinson’s disease model of Drosophila that possess a neuromuscular disorder showed improvement in their flight and climbing activity, suggesting the potential of Ashwagandha withanolides for the management of muscle repair and activity.

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Cellular and Molecular Mechanisms of Muscle Cell Differentiation in Ascidian Embryos

International Review of Cytology ◽

10.1016/s0074-7696(08)61209-7 ◽

1990 ◽

pp. 221-258 ◽

Cited By ~ 29

Author(s):

Noriyuki Satoh ◽

Takuya Deno ◽

Hiroki Nishida ◽

Takahito Nishikata ◽

Kazuhiro W. Makabe

Keyword(s):

Cell Differentiation ◽

Muscle Cell ◽

Molecular Mechanisms ◽

Muscle Cell Differentiation ◽

Ascidian Embryos

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Molecular Mechanisms of Smooth Muscle Cell Dedifferentiation and Development of Drugs for Regulation of Smooth Muscle Cell Differentiation.

The Journal of Japan Atherosclerosis Society ◽

10.5551/jat1973.26.2_87 ◽

1998 ◽

Vol 26 (2) ◽

pp. 87-91

Author(s):

Kazuhide HASEGAWA

Keyword(s):

Smooth Muscle ◽

Cell Differentiation ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Molecular Mechanisms ◽

Cell Dedifferentiation ◽

Muscle Cell Differentiation ◽

Smooth Muscle Cell Differentiation

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FoxO1a-Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion

Molecular and Cellular Biology ◽

10.1128/mcb.25.17.7645-7656.2005 ◽

2005 ◽

Vol 25 (17) ◽

pp. 7645-7656 ◽

Cited By ~ 25

Author(s):

Philippe R. J. Bois ◽

Vanessa F. Brochard ◽

Adèle V. A. Salin-Cantegrel ◽

John L. Cleveland ◽

Gerard C. Grosveld

Keyword(s):

Cell Differentiation ◽

Muscle Cell ◽

Cyclic Gmp ◽

Molecular Mechanisms ◽

Binding Activity ◽

Myoblast Fusion ◽

Muscle Cell Differentiation ◽

Dna Binding Activity ◽

Regulatory Circuits ◽

Myoblast Cell

ABSTRACT The regulatory circuits that orchestrate mammalian myoblast cell fusion during myogenesis are poorly understood. The transcriptional activity of FoxO1a directly regulates this process, yet the molecular mechanisms governing FoxO1a activity during muscle cell differentiation remain unknown. Here we show an autoregulatory loop in which FoxO1a directly activates transcription of the cyclic GMP-dependent protein kinase I (cGKI) gene and where the ensuing cGKI activity phosphorylates FoxO1a and abolishes its DNA binding activity. These findings establish the FoxO1a-to-cGKI pathway as a novel feedback loop that allows the precise tuning of myoblast fusion. Interestingly, this pathway appears to operate independently of muscle cell differentiation programs directed by myogenic transcription factors.

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Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway

Development ◽

10.1242/dev.122.12.3765 ◽

1996 ◽

Vol 122 (12) ◽

pp. 3765-3773 ◽

Cited By ~ 19

Author(s):

C. Shawber ◽

D. Nofziger ◽

J.J. Hsieh ◽

C. Lindsell ◽

O. Bogler ◽

...

Keyword(s):

Cell Differentiation ◽

Notch Signaling ◽

Cell Fate ◽

Muscle Cell ◽

Cellular Differentiation ◽

C2c12 Myoblasts ◽

Muscle Cell Differentiation ◽

Binding Factor ◽

Exogenous Expression ◽

Enhancer Of Split

Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.

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