关键词: Akt1, serine/threonine-protein kinase or AKT kinase 1 CLS, celastrol Celastrol DEX, dexamethasone DOX, doxorubicin ERK1/2, extracellular signal-regulated kinase 1/2 HSF1, Heat shock factor 1 HSP, heat shock protein ICC, immunocytochemistry MA, Muscular atrophy MAFbx, Muscle Atrophy F-box gene MMP, mitochondrial membrane potential MTCO1, Mitochondrially Encoded Cytochrome C Oxidase I MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MuRF1, Muscle RING Finger protein-1 Muscle atrophy NLS, nuclear localization signals RA, rheumatoid arthritis Rhynchophylline Ryn, Rhynchophylline SMA, spinal muscular atrophy Skeletal muscles VDAC, voltage-dependent anion channel mPTP, mitochondrial permeability transition pore

来  源:   DOI:10.1016/j.jsps.2022.06.008   PDF(Pubmed)

Abstract:
Muscular atrophy (MA) is a disease of various origins, i.e., genetic or the most common, caused by mechanical injury. So far, there is no universal therapeutic model because this disease is often progressive with numerous manifested symptoms. Moreover, there is no safe and low-risk therapy dedicated to muscle atrophy. For this reason, our research focuses on finding an alternative method using natural compounds to treat MA. This study proposes implementing natural substances such as celastrol and Rhynchophylline on the cellular level, using a simulated and controlled atrophy process. Methods: Celastrol and Rhynchophylline were used as natural compounds against simulated atrophy in C2C12 cells. Skeletal muscle C2C12 cells were stimulated for the differentiation process. Atrophic conditions were obtained by the exposure to the low concertation of doxorubicin and validated by FoxO3 and MAFbx. The protective and regenerative effect of drugs on cell proliferation was determined by the MTT assay and MT-CO1, VDAC1, and prohibitin expression. Results: The obtained results revealed that both natural substances reduced atrophic symptoms. Rhynchophylline and celastrol attenuated atrophic cells in the viability studies, morphology analysis by diameter measurements, modulated prohibitin VDAC, and MT-CO1 expression. Conclusions: The obtained results revealed that celastrol and Rhynchophylline could be effectively used as a supportive treatment in atrophy-related disorders. Thus, natural drugs seem promising for muscle regeneration.
摘要:
肌肉萎缩(MA)是一种多种起源的疾病,即,遗传或最常见的,机械损伤造成的。到目前为止,没有通用的治疗模式,因为这种疾病通常是进行性的,有许多明显的症状。此外,目前尚无针对肌肉萎缩的安全低危疗法.出于这个原因,我们的研究重点是寻找一种使用天然化合物治疗MA的替代方法。这项研究提出了在细胞水平上实施天然物质,如雷公藤红素和钩藤碱,使用模拟和控制的萎缩过程。方法:以雷公藤多酚和钩藤碱作为天然化合物,对抗C2C12细胞的模拟萎缩。刺激骨骼肌C2C12细胞进行分化过程。通过暴露于阿霉素的低浓度获得了萎缩性条件,并通过FoxO3和MAFbx进行了验证。通过MTT测定和MT-CO1,VDAC1和阻断素表达确定药物对细胞增殖的保护和再生作用。结果:获得的结果表明,两种天然物质均可减少萎缩性症状。在生存力研究中,钩藤碱和雷公藤红素减毒的萎缩性细胞,通过直径测量进行形态学分析,调制阻抑素VDAC,和MT-CO1表达。结论:所获得的结果表明,雷公藤红素和钩藤碱可以有效地用作萎缩相关疾病的支持治疗。因此,天然药物对肌肉再生似乎很有希望。
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