Salvadori Laura, Paiella Martina, Castiglioni Beatrice, Belladonna Maria Laura, Manenti Tommaso, Ercolani Catia, Cornioli Luca, Clemente Nausicaa, Scircoli Andrea, Sardella Roccaldo, Tensi Leonardo, Astolfi Andrea, Barreca Maria Letizia, Chiappalupi Sara, Gentili Giulia, Bosetti Michela, Sorci Guglielmo, Filigheddu Nicoletta, Riuzzi Francesca
Department of Translational Medicine, University of Piemonte Orientale, Novara 28100, Italy; Interuniversity Institute of Myology (IIM), Perugia 06132, Italy.
Department Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.
Biomed Pharmacother. 2024 May;174:116517. doi: 10.1016/j.biopha.2024.116517. Epub 2024 Apr 3.
Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties. Thus, considering that a chronic low-grade inflammatory state predisposes to both osteoporosis and sarcopenia, we tested a standardized hydroalcoholic extract of EQ in in vitro models of muscle atrophy [C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ), excess glucocorticoids (dexamethasone), or the osteokine, receptor activator of nuclear factor kappa-B ligand (RANKL)] and osteoclastogenesis (RAW 264.7 cells treated with RANKL). We found that EQ counteracted myotube atrophy, blunting the activity of several pathways depending on the applied stimulus, and reduced osteoclast formation and activity. By in silico target fishing, IKKB-dependent nuclear factor kappa-B (NF-κB) inhibition emerges as a potential common mechanism underlying EQ's anti-atrophic effects. Consumption of EQ (500 mg/kg/day) by pre-geriatric C57BL/6 mice for 3 months translated into: i) maintenance of muscle mass and performance; ii) restrained myofiber oxidative shift; iii) slowed down age-related modifications in osteoporotic bone, significantly preserving trabecular connectivity density; iv) reduced muscle- and spleen-related inflammation. EQ can preserve muscle functionality and bone remodeling during aging, potentially valuable as a natural treatment for osteosarcopenia.
年龄相关性骨肌减少症是一种尚未解决的综合征,其特征是骨组织(骨质减少)和骨骼肌组织(肌减少症)同时丧失,从而增加跌倒、活动障碍、发病率和死亡率。重塑过程中骨吸收不平衡以及蛋白质过度分解,尤其是快速型II肌球蛋白重链(MyHC-II)亚型和肌纤维代谢转变,分别是老年人骨骼和肌肉退化的主要原因。问荆(EQ)是一种传统上因其抗炎特性而被推荐用于多种病理状况的植物。因此,鉴于慢性低度炎症状态易导致骨质疏松症和肌减少症,我们在肌肉萎缩的体外模型[用促炎细胞因子(TNFα/IFNγ)、过量糖皮质激素(地塞米松)或骨因子、核因子κB受体激活剂配体(RANKL)处理的C2C12肌管]和成骨细胞生成(用RANKL处理的RAW 264.7细胞)中测试了标准化的问荆水醇提取物。我们发现,问荆可抵消肌管萎缩,根据所施加的刺激抑制多种信号通路的活性,并减少破骨细胞的形成和活性。通过计算机靶点筛选,依赖IKKB的核因子κB(NF-κB)抑制作为问荆抗萎缩作用的潜在共同机制出现。老年前C57BL/6小鼠连续3个月每天摄入500mg/kg问荆可带来以下结果:i)维持肌肉质量和性能;ii)抑制肌纤维氧化转变;iii)减缓骨质疏松性骨的年龄相关变化,显著保留小梁连接密度;iv)减轻肌肉和脾脏相关炎症。问荆可在衰老过程中维持肌肉功能和骨骼重塑,作为骨肌减少症的一种天然治疗方法可能具有重要价值。