• 한국식품영양학회지
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• 제37권5호
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• pp.273-281
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• 2024

Skeletal muscle is an organ that regulates biological metabolic energy. Its dysfunction causes decline of body functions and disability, thus deteriorating the overall quality of life. Various materials are being developed with an anti-sarcolytic effect. However, anti-sarcolytic effect of Sinomenium acutum rhizomes extract (SAE) remains unclear. Therefore, this study aimed to investigate anti-muscle atrophy effects of SAE and its alkaloids, including sinomenine (SIN), magnoflorine (MF), acutumine (ACU), and N-ferultyramine (NFT) isolated from SAE, on dexamethasone (Dex)-induced myotubules. C2C12 myogenic cells differentiated for 6 days were treated with 1 mM Dex for 24 hours. Induction of muscular atrophy was confirmed by a decrease in myogenin expression. We found that Dex increased expression levels of muscle-specific ubiquitin ligases MuRF1 and MAFbx/atrogin-1. However, mRNA and protein levels of these muscle-specific ubiquitin ligases were significantly reduced by cotreatment with SIN, MF, and NFT in myotubes. Glucose uptake reduced by Dex in myotubules were also restored by SIN, MF, and NFT treatments. These results suggest that SIN, MF, and NFT can reduce muscle wasting and enhance glucose uptake in Dex-treated myotubes, highlighting their potential as therapeutic agents to prevent muscle atrophy.

• Journal of Oral Medicine and Pain
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• 제47권4호
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• pp.217-221
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• 2022

Neurogenic muscular atrophy is muscle wasting and weakness caused by trauma or disease of the nerve that innervates the muscle. We describe a case of unilateral trigeminal neuropathy and neurogenic muscular atrophy of the masticatory muscle caused by a tumor in the foramen ovale. A 59-year-old man visited our clinic complaining of difficulty in right-sided mastication. There were no evident clinical signs and symptoms of temporomandibular disorder. However, severe atrophy of the right masseter and temporalis muscles and hypesthesia of the right side mandibular nerve area were confirmed. Through T1 and T2 signals on magnetic resonance imaging (MRI), a mass suspected of a neurogenic tumor was observed in the foramen ovale and cavernous sinus. Severe atrophy of all masticatory muscles on the right side was observed. This rare case shows trigeminal neuropathy caused by a tumor around the foramen ovale and atrophy of the ipsilateral masticatory muscles. For an accurate diagnosis, it is essential to identify the underlying cause of muscle atrophy with neurologic symptoms present. This can be done through a more detailed clinical examination, including sensory testing and brain MRI, and consider a referral to neurology or neurosurgery for the differential diagnosis of the intracranial disorder.

• Journal of Microbiology and Biotechnology
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• 제34권2호
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• pp.270-279
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• 2024

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

• Journal of Ginseng Research
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• 제48권1호
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• pp.52-58
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• 2024

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.495-505
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• 2024

Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 μM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.

• Annals of Geriatric Medicine and Research
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• 제22권4호
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• pp.167-175
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• 2018

Sarcopenia, a common clinical syndrome in older adults, is defined as decreased muscle mass, strength, and physical performance. Since sarcopenia is associated with the incidence of functional decline, falls, and even mortality in older adults, researchers and health care providers have been keen to accumulate clinical evidence to advocate the screening and prevention of sarcopenia progression in older adults. The factors that may accelerate the loss of muscle mass and function include chronic diseases, inactivity, and deficiency in appropriate nutritional support. Among these, nutritional support is considered an initial step to delay the progression of muscle wasting and improve physical performance in community-dwelling older adults. However, a nationwide study suggested that most Korean older adults do not consume sufficient dietary protein to maintain their muscle mass. Furthermore, considering age-associated anabolic resistance to dietary protein, higher protein intake should be emphasized in older adults than in younger people. To develop a dietary protein recommendation for older adults in Korea, we reviewed the relevant literature, including interventional studies from Korea. From these, we recommend that older adults consume at least 1.2 g of protein per kg of body weight per day (g/kg/day) to delay the progression of muscle wasting. The amount we recommend (1.2 g/kg/day) is 31.4% higher than the previously suggested recommended daily allowance (i.e., 0.91 g/kg/day) for the general population of Korea. Also, evidence to date suggests that the combination of exercise and nutritional support may enhance the beneficial effects of protein intake in older adults in Korea. We found that the current studies are insufficient to build population-based guidelines for older adults, and we call for further researches in Korea.

• Journal of Korean Biological Nursing Science
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• 제14권2호
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• pp.129-138
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• 2012

Purpose: Cachexia is a complex metabolic syndrome associated with wasting of skeletal muscle which contributes to nearly one-third of all cancer deaths. Cachexia lowers the frequency of response to chemotherapy and radiation and ultimately can impact survival as well as quality of life during treatment. NF-kappa B is one of the most important molecular mediators of cachexia. In this study, therefore, possible candidates for inhibitors of NF-kappa B were searched. Methods: Amino acids that regulate cellular redox potential by adjusting the level of NAD/NADH ratio, such as aspartate, pyruvate, and isocitrate were selected. Results: Pyruvate effectively inhibited luciferase activity in TNF-stimulated 293T cells transfect with an NF-kB dependent luciferase reporter vector. Pyruvate also showed protective effect on muscle atrophy of differentiated C2C12 myocyte induced by TNF/IFN. Conclusion: We might be able to develop the nutritional management strategy for cancer cachexia patients with pyruvate supplementation.

• 생명과학회지
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• 제33권12호
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• pp.1036-1045
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• 2023

골격근량과 근력의 점진적인 감소를 특징으로 하는 근감소증은 고령화 인구에서 중요한 문제이다. 본 연구는 콩잎 추출물(Soybean Leaf extracts, SL)의 덱사메타손으로 유도된 근위축에 대한 치료적 가능성을 세포 및 동물 모델에서 조사하였다. 세포 실험 결과, SL은 C2C12 근섬유의 형태, 밀도 및 크기가 보존되어 통계적으로 유의미한 수준으로 덱사메타손에 의해 유발된 근위축을 완화하는 것으로 나타났다. 또한, SL 처리는 주요 근육 위축 조절 인자인 muscle RING-finger protein-1 (MuRF1)과 muscle atrophy F-box (MAFbx)의 발현을 mRNA 및 단백질 수준 모두에서 유의하게 하향 조절하였다. 마우스 모델에서 SL 투여는 특히 덱사메타손으로 인한 체중 감소와 근육 소모를 상쇄하여 비복근과 전경골근의 근육량을 보존하는 것으로 나타났다. 기능적으로도 SL을 투여한 마우스는 악력과 트레드밀 지구력이 향상되어 근육 성능이 개선되었다. 또한 SL은 골격근에서 근위축 관련 단백질인 MAFbx의 발현을 억제하여 덱사메타손 유도 근위축에 대한 보호 역할을 보여주었다. 이러한 연구 결과를 종합해 볼 때 SL은 근감소증과 같은 근육 소모 질환을 개선할 수 있는 유망한 천연 치료제가 될 수 있음을 시사한다.

• Journal of Digestive Cancer Research
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• 제5권2호
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• pp.97-104
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• 2017

Cancer cachexia는 지방조직과 근육계 조직의 손실에 따른 체중의 현격한 감소를 특징으로 하고 있어 궁극적으로는 암 치료제에 대한 반응을 낮출 뿐만 아니라, 삶의 양은 물론 질도 낮추게 되는 시급히 해결되어야 하는 미충족 의료수요중의 하나이다. 아직까지 임상에서는 수많은 노략에도 불구하고 일부 완화시킬 수 있는 약제가 있기는 하나, 전반적으로 해결이 가능한 약제나 치료 방법이 아직은 없는 실정이다. 그러므로 이를 해결할 수 있는 방법으로 동물모델이 필요한 질환이라 하겠다. 이러한 배경하에 연구자 등은 우선 동물모델을 수립하고 이를 기반으로 적절한 치료제를 개발하기 목적으로 본 연구에서는 C26 대장 선암 세포를 이용한 Cancer cachexia 동물모델을 수립하여 이 모델에서의 변화를 소개함으로써 향후 더 진보된 치료제 개발이나 병태생리를 연구하는데 도움을 주고자 본 연구를 시행하여 다음과 같은 결과를 얻을 수 있었다. C26 adenocarcinoma를 대퇴부 주입 후 시간 경과에 따라 몸무게의 변화가 현저하여 2주 이후에 유의한 몸무게의 감소, 식욕부진, 활동감소가 관찰되었고, 이때의 혈청 Cytokine 및 이를 조절하는 여러가지 전사인자의 변화가 선행되었고, 현저한 근육계의 근감소가 관찰되었으며, 실험동물은 3주에 40%가 사망하는 변화를 보였다. 연구자 등은 본 동물모델은 향후 새로운 치료약제 개발이나 Cancer cachexia 병태생리 연구에 매우 도움이 되는 수립하기 간편하며, 기저 분자생물학적 변화를 관찰할 수 있는 우수한 Cancer cachexia 모델이라 결론지을 수 있었다.