Ampelopsin attenuates the atrophy of skeletal muscle from D-gal-induced aging rats through activating AMPK/SIRT1/PGC-1α signaling cascade

Ampelopsin attenuates the atrophy of skeletal muscle from D-gal-induced aging rats through activating AMPK/SIRT1/PGC-1α signaling cascade
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Ampelopsin 通过激活 AMPK/SIRT1/PGC-1α 信号级联来减轻 d-gal 诱导的衰老大鼠骨骼肌萎缩。

DOI:
10.1016/j.biopha.2017.03.070
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发表时间:
2017-06-01
影响因子:
7.5
通讯作者:
Chen, Ning
Chen, Ning
中科院分区:
医学2区
文献类型:
--
作者:
Kou, Xianjuan;Li, Jie;Chen, Ning

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骨骼肌萎缩与氧化损伤、过度凋亡和功能失调性自噬密切相关。蛇葡萄素是一种天然黄酮类化合物,具有抗炎、抗氧化、保肝等多种生物学功能。Sprague-Dawley(SD)大鼠连续6周腹腔注射D-半乳糖(D-gal)150 mg/kg.d后,骨骼肌明显萎缩,肌质量/体质量比、肌纤维横截面积和肌纤维直径均显著降低。相反,相同剂量的D-gal和100或200 mg/kg.d剂量的DHM联合给药可减轻与骨骼肌萎缩相关的这些标志的减少。此外,D-gal给药可导致骨骼肌中明显的细胞凋亡和受损的自噬,这可在DHM处理后减轻,这是由于其降低泛素和Atrogin-1/MAFbx以及上调AMPK和SIRT 1信号通路的作用。因此,DHM可能是预防和治疗骨骼肌萎缩的潜在候选药物。(C)2017年Elsevier Masson SAS。All rights reserved.
The atrophy of skeletal muscle is highly correlated with oxidative damage, excessive apoptosis and dysfunctional autophagy. Ampelopsin, a natural flavonoid, has multiple biological functions including anti-inflammatory, anti-oxidative, and hepatoprotective functions. Sprague-Dawley (SD) rats subjected to intraperitoneal injection of D-galactose (D-gal) at the dose of 150 mg/kg.d revealed an obvious atrophy of skeletal muscle with significantly reduced muscle mass/body mass ratio, cross-sectional area and fiber diameter of skeletal muscle in D-gal-induced aging rats when compared to normal control rats without D-gal administration for 6 consecutive weeks. In contrast, the combinatorial administration of D-gal at the identical dose and DHM at the dose of 100 or 200 mg/kg.d could alleviate the reduction of these hallmarks associated with the atrophy of skeletal muscle. In addition, D-gal administration could result in obvious apoptosis and impaired autophagy in skeletal muscle, which could be mitigated upon DHM treatment due to its role in decreasing ubiquitin and Atrogin-1/MAFbx and up-regulating AMPK and SIRT1 signal pathways. Therefore, DHM may be a potential candidate for the prevention and treatment of skeletal muscle atrophy associated aging process. (C) 2017 Elsevier Masson SAS. All rights reserved.