• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.427-436
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• 2018

The objective of this study was to analyze the concurrent treatment effects of ursolic acid (UA) and low-intensity treadmill exercise and to confirm the effectiveness of UA as an exercise mimetic to safely improve muscle atrophy-related diseases using Sprague-Dawley (SD) rats with skeletal muscle atrophy. Significant muscle atrophy was induced in male SD rats through hind limb immobilization using casting for 10 days. The muscle atrophy-induced SD rats were group into four: SED, sedentary; UA, daily intraperitoneal UA injection, 5 mg/kg; EX, low-intensity (10-12 m/min, $0^{\circ}$ grade) treadmill exercise; and UEX, daily intraperitoneal UA injection, 5 mg/kg, and low-intensity (10-12 m/min, $0^{\circ}$ grade) treadmill exercise. After 8 weeks of treatment, endurance capacity was analyzed using a treadmill, and tissues were extracted for analysis of visceral fat mass, body weight, muscle mass, expression of muscle atrophy- and hypertrophy-related genes, and endurance capacity. Although the effects of body weight gain control, muscle mass increase, and endurance capacity improvement were inadequate in the UA group, significant results were confirmed in the UEX group. The UEX group had significantly reduced body weight and visceral fat, significantly improved mass of tibialis anterior and gastrocnemius muscles, and significantly decreased atrophy-related gene expression of MuRF1 and atrogin-1, but did not have significant change in hypertrophy-related gene expression of Akt and mTOR. The endurance capacity was significantly improved in the EX and UEX groups. These data suggest that concurrent treatment with low-intensity exercise and UA is effective for atrophy-related physical dysfunctions.

• Journal of Korean Medicine Rehabilitation
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• v.27 no.4
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• pp.1-9
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• 2017

Objectives Oxidative stress, in which antioxidant proteins and scavenger protection are overwhelmed by reactive oxygen species (ROS) production, is recognized as one of central causes of disuse muscle atrophy. In this study, the hypothesis that oral treatment with Dangguibohyul-tang (Dangguibuxuetang) could attenuate immobilization-induced skeletal muscle atrophy was tested. Methods The hindlimb immobilization was performed with casting tape to keep the left ankle joint in a fully extended position. The Rats in Dangguibohyul-tang treated group (DGBHT) (n=10) were orally administrated Dangguibohyul-tang water extract, and rats of Control group (n=10) were given with saline only. After 2 weeks of immobilization, the morphology of right and left gastrocnemius muscles in both DGBHT and Control groups were assessed by hematoxylin and eosin staining. Results Dangguibohyul-tang water extract represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. Moreover, the treatment with Dangguibohyul-tang extract significantly enhanced the Cu/Zn-SOD activities in gastrocnemius muscle compared with Control group. Conclusions Thses results suggest that Dangguibohyul-tang has protective effects against immobilization-induced muscle atrophy by increasing the Cu/Zn-SOD activities in gastrocnemius muscle.

• The Korean Journal of Food And Nutrition
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• v.30 no.2
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• pp.371-377
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• 2017

Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.585-592
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• 2021

Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise (CC, n = 8), cisplatin (1 mg/kg) + resistance exercise (CRE, n = 9) group, and cisplatin (1 mg/kg) + aerobic exercise (CAE, n = 11). The CRE group performed progressive ladder exercise (starting with 10% of body weight on a 1-m ladder with 2-cm-interval grids, at 85°) for 8 weeks. The CAE group exercised by treadmill running (20 m/min for 60 min daily, 4 times/week) for 8 weeks. Compared with the CC group, the levels of the autophagy-related factors BNIP3, Beclin 1, LC3-II/I ratio, p62, and FOXO3a in the gastrocnemius and soleus muscles were significantly decreased in the CRE and CAE groups. The CRE and CAE groups further showed significantly decreased MuRF 1 and Atrogin-1 levels and increased phosphorylation of AKT, FOXO3a, and PGC1-α. These results suggest that both ladder and aerobic exercise directly affected muscle wasting by modulating the AKT/PGC1-α/FOXO3a signaling pathways regardless of the skeletal muscle type.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.1
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• pp.47-63
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• 2008

Objectives : Eucommiae cortex is reported that it helps bone and skeletal muscle stronger. In case of bone, many report is presented, but reports related to skeletal muscle are rarely existed. So in order to investigate effects of Eucommiae cortex on the skeletal muscle atrophy following stroke, cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) in the rats. Methods : In order to induce MCAO rats, nylon suture was advanced and then blocked middle cerebral artery(MCA). Water extract of Eucommiae cortex was treated for 15 days, once a day orally, after the MCAO. Effects were evaluated with muscle weights, muscle fiber type composition, cross-sectioned area of muscle fibers in soleus and gastrocnemius of the unaffected and affected hind limbs. And MyoD protein expression in gastrocnemius was demonstrated with immunohistochemistry and western blotting. Results : In the affected hind limb of the MCAO rats, muscle weight loss of gastrocnemius and tibialis anterior muscles were attenuated by Eucommiae cortex treatment. In soleus muscle of the affected hind limb of the MCAO rats, increase of type-I fibers and decrease of type-II fibers were induced by Eucommiae cortex treatment. In soleus muscle of the affected hind limb of the MCAO rats, decrease of cross-sectioned areas of type-I fibers was attenuated by Eucommiae cortex treatment. In gastrocnemius muscle of the affected hind limb of the MCAO rats, increase of type-I fibers and decrease of type-II fibers were induced by Eucommiae cortex treatment. In gastrocnemius muscle of the affected hind limb of the MCAO rats, decreases of cross-sectioned areas of type-I and type-II fibers were attenuated by Eucommiae cortex treatment. In gastrocnemius muscle of the affected and unaffected hind limb of the MCAO rats, MyoD expressions were increased by Eucommiae cortex treatment. Conclusions : These results suggest that Eucommiae cortex has a protective effect against muscle atrophy, through the inhibition of the muscle cell apoptosis, following the central nervous system demage.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.12-19
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• 2024

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

• Journal of The Korean Society of Integrative Medicine
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• v.6 no.4
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• pp.75-82
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• 2018

Purpose : The present study tested the hypothesis that acupressure at Zusanli(ST36) would attenuate immobilization-induced skeletal muscle atrophy. Methods : The left hind limb was immobilized using casting tape (ST36 group, n=10), and the animals were then treated daily with a pressure needle at ST36. Ten untreated animals with hind limb immobilization and no treatment served as a control group (n=10). After 2 weeks of immobilization, The body weight changes of rats were evaluated and the morphologies of the right and left gastrocnemius muscles in both the ST36 and control groups were assessed by hematoxylin and eosin staining. The levels of malondialdehyde (MDA) of gastrocnemius muscles were observed. Results : The acupressure at the accupoint of Zusanli conferred significant protection against reductions in left gastrocnemius muscle weights and average cross-sectional muscle areas in the ST36 group as compared with those in the control group. Moreover, the acupressure at the ST36 point significantly reduced malondialdehyde (MDA) activity in the gastrocnemius muscles as compared with that in the control group. Conclusion : These results suggest that acupressure at the accupoint of Zusanli provides protection against immobilization-induced muscle atrophy by decreasing MDA activity in gastrocnemius muscles.

• 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.