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Decreased eccentric exercise-induced macrophage infiltration in skeletal muscle after supplementation with a class of ginseng-derived steroids.

Yu SH, Huang CY, Lee SD, Hsu MF, Wang RY, Kao CL, Kuo CH - PLoS ONE (2014)

Bottom Line: Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng.In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise.Furthermore, high doses should be avoided in formulating ginseng-based products.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei City, Taiwan, Republic of China; Department of Leisure Industry and Health Promotion, National Ilan University, Yilan County, Taiwan, Republic of China.

ABSTRACT
Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.

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Muscle strength, muscle regeneration, M2 macrophages and muscle fiber types.(A) Bars represent the suspension time (seconds) in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. (B) Representative histopathological analysis of muscle section from soleus muscle with H&E staining. Arrowheads indicate centronucleation. Scoring of each group is shown on the right. (C) Representative immunohistochemical staining of CD163-positive cells (brown color) in a soleus muscle section. Nucleolus was labeled with eosin staining (blue color). Original magnification was 400x, and scoring of CD163-positive cells is shown on the right. (D) Bars represent the relative quantification of IL-10 mRNA expression levels normalized to 18S rRNA. (E) Bars represent the percentage of muscle fiber types in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. In (A–E), data are presented as the mean ± SEM. *p<0.05 compared with the control group. Scale bar  = 50 µm.
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pone-0114649-g007: Muscle strength, muscle regeneration, M2 macrophages and muscle fiber types.(A) Bars represent the suspension time (seconds) in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. (B) Representative histopathological analysis of muscle section from soleus muscle with H&E staining. Arrowheads indicate centronucleation. Scoring of each group is shown on the right. (C) Representative immunohistochemical staining of CD163-positive cells (brown color) in a soleus muscle section. Nucleolus was labeled with eosin staining (blue color). Original magnification was 400x, and scoring of CD163-positive cells is shown on the right. (D) Bars represent the relative quantification of IL-10 mRNA expression levels normalized to 18S rRNA. (E) Bars represent the percentage of muscle fiber types in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. In (A–E), data are presented as the mean ± SEM. *p<0.05 compared with the control group. Scale bar  = 50 µm.

Mentions: Muscle strength was evaluated using a wire suspension test (Fig. 7A). Suspension time increased by 40–50% in all doses of DS treatment compared to control rats. Regenerative muscle fibers and CD163-positive cells were identified by centronucleation (Fig. 7A) and brown color (Fig. 7B), respectively. Histological (Fig. 7B) and immunohistochemical (Fig. 7C) analyses show that 10 weeks of DS supplementation increased centronucleation and the number of CD163+ M2 macrophages in muscle above saline control level, indicating increased muscle fiber regeneration. Consistent with these data, IL-10 mRNA expression was elevated in DS-treated rats relative to saline controls (Fig. 7D). No effect of DS supplementation on muscle fiber type composition was observed (Fig. 7E).


Decreased eccentric exercise-induced macrophage infiltration in skeletal muscle after supplementation with a class of ginseng-derived steroids.

Yu SH, Huang CY, Lee SD, Hsu MF, Wang RY, Kao CL, Kuo CH - PLoS ONE (2014)

Muscle strength, muscle regeneration, M2 macrophages and muscle fiber types.(A) Bars represent the suspension time (seconds) in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. (B) Representative histopathological analysis of muscle section from soleus muscle with H&E staining. Arrowheads indicate centronucleation. Scoring of each group is shown on the right. (C) Representative immunohistochemical staining of CD163-positive cells (brown color) in a soleus muscle section. Nucleolus was labeled with eosin staining (blue color). Original magnification was 400x, and scoring of CD163-positive cells is shown on the right. (D) Bars represent the relative quantification of IL-10 mRNA expression levels normalized to 18S rRNA. (E) Bars represent the percentage of muscle fiber types in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. In (A–E), data are presented as the mean ± SEM. *p<0.05 compared with the control group. Scale bar  = 50 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263678&req=5

pone-0114649-g007: Muscle strength, muscle regeneration, M2 macrophages and muscle fiber types.(A) Bars represent the suspension time (seconds) in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. (B) Representative histopathological analysis of muscle section from soleus muscle with H&E staining. Arrowheads indicate centronucleation. Scoring of each group is shown on the right. (C) Representative immunohistochemical staining of CD163-positive cells (brown color) in a soleus muscle section. Nucleolus was labeled with eosin staining (blue color). Original magnification was 400x, and scoring of CD163-positive cells is shown on the right. (D) Bars represent the relative quantification of IL-10 mRNA expression levels normalized to 18S rRNA. (E) Bars represent the percentage of muscle fiber types in the control and 20 mg/kg DS, 60 mg/kg DS, and 120 mg/kg DS groups. In (A–E), data are presented as the mean ± SEM. *p<0.05 compared with the control group. Scale bar  = 50 µm.
Mentions: Muscle strength was evaluated using a wire suspension test (Fig. 7A). Suspension time increased by 40–50% in all doses of DS treatment compared to control rats. Regenerative muscle fibers and CD163-positive cells were identified by centronucleation (Fig. 7A) and brown color (Fig. 7B), respectively. Histological (Fig. 7B) and immunohistochemical (Fig. 7C) analyses show that 10 weeks of DS supplementation increased centronucleation and the number of CD163+ M2 macrophages in muscle above saline control level, indicating increased muscle fiber regeneration. Consistent with these data, IL-10 mRNA expression was elevated in DS-treated rats relative to saline controls (Fig. 7D). No effect of DS supplementation on muscle fiber type composition was observed (Fig. 7E).

Bottom Line: Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng.In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise.Furthermore, high doses should be avoided in formulating ginseng-based products.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei City, Taiwan, Republic of China; Department of Leisure Industry and Health Promotion, National Ilan University, Yilan County, Taiwan, Republic of China.

ABSTRACT
Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.

Show MeSH
Related in: MedlinePlus