• Journal of Ginseng Research
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• v.46 no.3
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• pp.444-453
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• 2022

Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. Methods: C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4-5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. Results: CK treatment attenuated ER stress markers, such as eIF2a phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. Conclusion: These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.726-734
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• 2023

Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

• Journal of Life Science
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• v.33 no.12
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• pp.1036-1045
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• 2023

Sarcopenia, a condition characterized by the insidious loss of skeletal muscle mass and strength, represents a significant and growing healthcare challenge, impacting the mobility and quality of life of aging populations worldwide. This study investigated the therapeutic potential of soybean leaf extract (SL) for dexamethasone (Dexa)-induced muscle atrophy in vitro and in an in vivo model. In vitro experiments showed that SL significantly alleviated Dexa-induced atrophy in C2C12 myotube cells, as evidenced by preserved myotube morphology, density, and size. Moreover, SL treatment significantly reduced the mRNA and protein levels of muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx), key factors regulating muscle atrophy. In a Dexa-induced atrophy mouse model, SL administration significantly inhibited Dexa-induced weight loss and muscle wasting, preserving the mass of the gastrocnemius and tibialis anterior muscles. Furthermore, mice treated with SL exhibited significant improvements in muscle function compared to their counterparts suffering from Dexa-induced muscle atrophy, as evidenced by a notable increase in grip strength and extended endurance on treadmill tests. Moreover, SL suppressed the expression of muscle atrophy-related proteins in skeletal muscle, highlighting its protective role against Dexa-induced muscle atrophy. These results suggest that SL has potential as a natural treatment for muscle-wasting conditions, such as sarcopenia.

• The Journal of Korean Physical Therapy
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• v.16 no.2
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• pp.63-71
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• 2004

Denervated skeletal muscle produces muscle atrophy as well as changes at the neuromuscular junction which leads to terminal axonal sprouting and an ultrastructural remodeling. NT-3 is expressed in adult muscle and motoneurons. Normally NT-3 has a potential role in regulating adult neuromuscular jungtion and recovering following muscle atrophy. Also, it could influence synaptic neurotransmission between motoneurons and skeletal muscle cells. The purpose of this study was to investigate the effect of electrical stimulation therapy(EST) on NT-3 expression in neuromuscular junction following sciatic nerve transsection in rats. After EST application during 7 days, the immunoreactivity of NT-3 was increased in neuromuscular junction

• Journal of Korean Academy of Nursing
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• v.23 no.2
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• pp.207-223
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• 1993

Inpatients are mostly occupied in bed with restricted activity, nearly all patient populations are at risk for the occurrence of skeletal muscle atrophy due to decreased level of activity. Restriction of mobility is far greater in pediatric patients compared with adult patients since almost all the activities of daily living is performed by parents or caregivers. It could be assumed that pediatric patients are more vulnerable to skeletal muscle atrophy than adult patients, however, there have been no attempts to reduce the atrophy of developing muscle. Therefore it is important to determine the effect of exercise in developing muscle during decreased activity. The purpose of this study was to determine the effect of periodic weight support during hindlimb suspension on the mass and cross-sectional area of Type I and II fibers in developing soleus(Type I ) muscle. To examine the effectiveness of periodic weight support activity in maintaining mass and fiber size. the hindlimb of young female Wistar rats was suspended(HS) and half of these rats walked on a treadmill for 45min / day(15min every 4h) at 5m / min at a 15 grade(HS-WS). After 7days of hindlimb suspension, soleus wet weight was 28. 57% smaller and relative soleus weight was 28. 21% smaller in comparison with con-trol rats (p〈0.05) Soleus wet weight and relative soleus weight increased by 67.72% and 71.43% each with periodic weight support activity during hindlimb suspension (p〈0.01, p〈0.005), moreover soleus wet weight and relative soleus weight of the HS -WS rats were greater than those of the control group. No change was observed in fiber type percentage of the developing soleus muscle after 1 week of hindlimb suspension plus weight support activity. Type I and II fiber cross-sectional areas of the developing soleus muscle were 50.45% and 43.39% lower in the HS group than in the control group (p〈0.0001), type I and II fiber cross-sectional areas of the developing soleus were 24.49% and 29.93% greater in the HS - WS group than in the HS rats (p〈0.0001), whereas Type I and II fiber cross-sectional areas of HS - WS group were less than those of the control group, The results suggest that periodic weight support activity can ameliorate developing soleus muscle atrophy induced by hindlimb suspension, even in type II fibers that would not have been expected to be recruited by this type of neuromuscular demand. Clinical experimental study is needed to deter-mine the effect of periodic weight bearing exercise on developing atrophied leg muscle based on these results.

• Journal of Korean Medicine Rehabilitation
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• v.28 no.4
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• pp.1-9
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• 2018

Objectives Disuse muscle atrophy occurs in response to pathologies such as joint immobilization, inactivity or bed rest. Muscle disuse is accompanied by an increase in apoptotic signaling, which mediates some of the responses to unloading in the muscle. GB34 (Yanglingquan) is a acupuncture point on the lower leg and one of the most frequently used points in various skeletomuscular diseases. In this study, the hypothesis that the acupuncture at GB34 could attenuate immobilization-induced skeletal muscle atrophy was tested. Methods The left hindlimb immobilization was performed with casting tape in both GB34 group (n=10) and Control group (n=10). The rats in GB34 group were daily treated with acupuncture at GB34. After 2 weeks of immobilization, the morphology of right and left gastrocnemius muscles in both GB34 and Control groups were assessed by hematoxylin and eosin staining. To investigate the immobilization-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. Results GB34 group represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. The acupuncture at GB34 significantly reduced the immunoreactivity of BAX and increased the immunoreactivity of Bcl-2 in gastrocnemius muscle compared with Control group. Conclusions These results suggest that the acupuncture at GB34 has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle.

• Herbal Formula Science
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• v.25 no.4
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• pp.499-508
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• 2017

Objectives : Skeletal muscle atrophy occurs in response to a variety of conditions. The unloading to muscle occurs clinically in limb immobilization, bed rest, spinal cord injury and peripheral nerve damage, resulting in significant loss of muscle mass and force production. Muscle disuse is accompanied by an increase in apoptotic signaling, which mediates some of the responses to unloading in the muscle. In this study we tested the hypothesis that Daeyeoung-jeon extract would improve muscle recovery after reloading following disuse. Method : Twenty young male Sprague-Dawley rats were used for the studies. The hindlimb immobilization was performed with casting tape to keep the left ankle joint in a fully extended position. No intervention was performed on the right leg and used as intact region. The Rats in Daeyeoung-jeon treated group (DYJ) were orally administrated Daeyeoung-jeon water extract, and rats of Control group were given with saline only. After 2 weeks of immobilization, all animals were sacrificed, and the whole gastrocnemius muscles were dissected from both legs. The morphology of right and left gastrocnemius muscles in both DYJ and Control groups were assessed by hematoxylin and eosin staining. Moreover, to investigate the immobilization-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. Results : Daeyeoung-jeon represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. The treatment with Daeyeoung-jeon extract significantly reduced the immunoreactivity of BAX and increased the immunoreactivity of Bcl-2 in gastrocnemius muscle compared with Control group. Conclusion : Daeyeoung-jeon has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.1
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• pp.63-70
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• 2023

Purpose : Excessive alcohol causes damage to skeletal muscles, leading to the development of a specific disease entity called alcoholic myopathy. Chronic inflammation is related as an underlying mechanism for the loss of muscle mass induced by alcohol. Pro-inflammatory cytokines such as TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) play a role in this process. The acupuncture point Feng Shi (GB 31) is located on the midline of the lateral aspect of the thigh, above the transverse popliteal crease. This acupoint is used for the treatment of weakness, atrophy, numbness, and post-stroke symptoms of lower limbs. The purpose of this study was to investigate the effect of Feng Shi stimulation on muscle atrophy caused by chronic alcohol administration. Method : Young male Sprague-Dawley rats were randomly divided into three groups of eight each: Normal, Control, and GB31. The rats in the Control and GB31 groups were orally given 25 % ethanol (5 ㎖/kg, body weight) daily for 4 weeks. The Normal group was similarly administered saline. The acupressure at Feng Shi was treated to rats in the GB31 group. After 4 weeks, the body weight, muscle weight and cross-sectional area of gastrocnemius were assessed and the histological changes in gastrocnemius muscle fiber were observed by hematoxylin and eosin staining. Moreover, TNF-α and IL-6 expressions were immunohistochemistrically evaluated. Results : Acupressure stimulation at Feng Shi had a protective effect on the weight reduction of the gastrocnemius muscle caused by alcohol intake, and had an effect of suppressing anatomical change in muscle fiber and decreasing the average cross-sectional area. Also, the immunoreactivities of TNF-α and IL-6 in the GB31 group were decreased. Conclusion : These results suggest that acupressure at Feng Shi has protective effects on chronic alcohol-induced muscle atrophy by inhibiting pre-inflammatory proteins such as TNF-α and IL-6.

• Herbal Formula Science
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• v.24 no.4
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• pp.311-321
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• 2016

Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.387-396
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• 2022

Skeletal muscle accounts for about 40-50% of body weight and is an important tissue that performs various functions, such as maintaining posture, supporting soft tissues, maintaining body temperature, and respiration. Cancer, which occurs widely around the world, causes cancer cachexia accompanied by muscular atrophy, which reduces the effectiveness of anticancer drugs and greatly reduces the quality of life and survival rate of cancer patients. Therefore, research to improve cancer cachexia is ongoing. However, there are few studies on the link between cancer and muscle atrophy. Cancer cells exhibit distinct microenvironment and metabolism from tumor cells, including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), and insulin resistance due to the Warburg effect. Therefore, we summarize the microenvironment and metabolic characteristics of cancer cells, and the molecular mechanisms of muscle atrophy that can be affected by cytokine and insulin resistance. In addition, this suggests the possibility of improving cancer cachexia of substances affecting TAM, TAN, and Warburg effect. We also summarize the mechanisms identified so far through single agents and the signaling pathways mediated by them that may ameliorate cancer cachexia.