Limits...
The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice.

Kim JW, Ku SK, Han MH, Kim KY, Kim SG, Kim GY, Hwang HJ, Kim BW, Kim CM, Choi YH - Int. J. Mol. Med. (2015)

Bottom Line: In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner.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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute, Bio-Port Korea INC, Marine Bio-industry Development Center, Busan 619-912, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Representative gastrocnemius muscle histological images, taken from mice in the intact vehicle control or dexamethasone control groups. Samples from gastrocnemius muscle were separated and fixed in 10% neutral buffered formalin, then embedded in paraffin, sectioned and stained with H&E for general histo-pathological analysis or with Sirius red for the detection of collagen fibers, and the histopathological profiles of each sample were determined by light microscopy. (A) Intact vehicle control, (B) dexamethasone control, (C) 50 mg/kg oxymetholone-treated mice, (D) 500 mg/kg FS orally-treated mice, (E) 250 mg/kg FS mg/kg orally-treated mice, (F) 125 mg/kg FS orally-treated mice. Scale bars, 40 μm. FS, Fructus Schisandrae.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494578&req=5

f6-ijmm-36-01-0029: Representative gastrocnemius muscle histological images, taken from mice in the intact vehicle control or dexamethasone control groups. Samples from gastrocnemius muscle were separated and fixed in 10% neutral buffered formalin, then embedded in paraffin, sectioned and stained with H&E for general histo-pathological analysis or with Sirius red for the detection of collagen fibers, and the histopathological profiles of each sample were determined by light microscopy. (A) Intact vehicle control, (B) dexamethasone control, (C) 50 mg/kg oxymetholone-treated mice, (D) 500 mg/kg FS orally-treated mice, (E) 250 mg/kg FS mg/kg orally-treated mice, (F) 125 mg/kg FS orally-treated mice. Scale bars, 40 μm. FS, Fructus Schisandrae.

Mentions: In the histopathological analysis of muscle atrophy, we observed that marked and classic catabolic muscle atrophic changes, including diminishing muscle fibers, microvacuolation and focal fibrosis in the muscle bundles were induced by treatment with dexamethasone, as well as a significant decrease in the mean muscle fiber diameters. An increase in the number of regions occupied by collagen fibers in muscle bundles was detected in the mice in the dexamethasone control group compared with the mice in the intact vehicle control group (Table VI and Fig. 6). These atrophic changes were markedly decreased by treatment with FS in a dose-dependent manner. The muscle atrophic changes were also significantly inhibited in the oxymetholone-treated mice compared with the dexamethasone control mice. Moreover, a marked and significant increase in nitrotyrosine-, 4-HNE- and iNOS-immunoreactive fibers was also observed in the mice in the dexamethasone control group; however, FS normalized these dexamethasone-related changes in a dose-dependent manner (Table VI). Oxymetholone also significantly decreased the nitrotyrosine-, 4-HNE- and iNOS-positive muscle fiber numbers compared with those obseved in the mice in the dexamethasone control group. Furthermore, the numbers of immunoreactive fibers stained for myostatin, a potent negative regulator of muscle growth, were significantly increased in the mice in the dexamethasone control group. However, FS significantly normalized these changes and oxymetholone also significantly decreased the numbers of myostatin-positive muscle fibers compared with those observed in the mice in the dexamethasone control group.


The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice.

Kim JW, Ku SK, Han MH, Kim KY, Kim SG, Kim GY, Hwang HJ, Kim BW, Kim CM, Choi YH - Int. J. Mol. Med. (2015)

Representative gastrocnemius muscle histological images, taken from mice in the intact vehicle control or dexamethasone control groups. Samples from gastrocnemius muscle were separated and fixed in 10% neutral buffered formalin, then embedded in paraffin, sectioned and stained with H&E for general histo-pathological analysis or with Sirius red for the detection of collagen fibers, and the histopathological profiles of each sample were determined by light microscopy. (A) Intact vehicle control, (B) dexamethasone control, (C) 50 mg/kg oxymetholone-treated mice, (D) 500 mg/kg FS orally-treated mice, (E) 250 mg/kg FS mg/kg orally-treated mice, (F) 125 mg/kg FS orally-treated mice. Scale bars, 40 μm. FS, Fructus Schisandrae.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494578&req=5

f6-ijmm-36-01-0029: Representative gastrocnemius muscle histological images, taken from mice in the intact vehicle control or dexamethasone control groups. Samples from gastrocnemius muscle were separated and fixed in 10% neutral buffered formalin, then embedded in paraffin, sectioned and stained with H&E for general histo-pathological analysis or with Sirius red for the detection of collagen fibers, and the histopathological profiles of each sample were determined by light microscopy. (A) Intact vehicle control, (B) dexamethasone control, (C) 50 mg/kg oxymetholone-treated mice, (D) 500 mg/kg FS orally-treated mice, (E) 250 mg/kg FS mg/kg orally-treated mice, (F) 125 mg/kg FS orally-treated mice. Scale bars, 40 μm. FS, Fructus Schisandrae.
Mentions: In the histopathological analysis of muscle atrophy, we observed that marked and classic catabolic muscle atrophic changes, including diminishing muscle fibers, microvacuolation and focal fibrosis in the muscle bundles were induced by treatment with dexamethasone, as well as a significant decrease in the mean muscle fiber diameters. An increase in the number of regions occupied by collagen fibers in muscle bundles was detected in the mice in the dexamethasone control group compared with the mice in the intact vehicle control group (Table VI and Fig. 6). These atrophic changes were markedly decreased by treatment with FS in a dose-dependent manner. The muscle atrophic changes were also significantly inhibited in the oxymetholone-treated mice compared with the dexamethasone control mice. Moreover, a marked and significant increase in nitrotyrosine-, 4-HNE- and iNOS-immunoreactive fibers was also observed in the mice in the dexamethasone control group; however, FS normalized these dexamethasone-related changes in a dose-dependent manner (Table VI). Oxymetholone also significantly decreased the nitrotyrosine-, 4-HNE- and iNOS-positive muscle fiber numbers compared with those obseved in the mice in the dexamethasone control group. Furthermore, the numbers of immunoreactive fibers stained for myostatin, a potent negative regulator of muscle growth, were significantly increased in the mice in the dexamethasone control group. However, FS significantly normalized these changes and oxymetholone also significantly decreased the numbers of myostatin-positive muscle fibers compared with those observed in the mice in the dexamethasone control group.

Bottom Line: In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner.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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute, Bio-Port Korea INC, Marine Bio-industry Development Center, Busan 619-912, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus