In the present study, we aimed to determine whether
ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of
dexamethasone-induced
muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with
dexamethasone to induce
muscle atrophy. Some mice were treated with various concentrations of FS or
oxymetholone, a 17α-alkylated
anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum
creatine and
creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum
lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by
dexamethasone in a dose-dependent manner. Treatment with FS also prevented the
dexamethasone-induced increase in serum
creatine and
creatine kinase levels, histopathological muscle fiber microvacuolation and
fibrosis, and the immunoreactivity of muscle fibers for
nitrotyrosine,
4-hydroxynonenal,
inducible nitric oxide synthase and
myostatin. In addition, the destruction of the gastrocnemius
antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the
mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in
muscle protein degradation),
myostatin (a potent negative regulator of muscle growth) and
sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the
mRNA expression of
phosphatidylinositol 3-kinase, Akt1,
adenosine A1 receptor and
transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of
protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg
oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on
muscle atrophy induced by
dexamethasone, by exerting anti-inflammatory and
antioxidant effects on muscle fibers, which may be due to an increase in
protein synthesis and a decrease in protein degradation.