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虾青素通过调节肠道微生物群来减缓索拉非尼治疗荷瘤 H22 小鼠的骨骼肌萎缩。

Astaxanthin slows down skeletal muscle atrophy in H22 tumor-bearing mice during sorafenib treatment by modulating the gut microbiota.

机构信息

State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of, China, Qingdao, Shandong 266003, China.

出版信息

Food Funct. 2024 Jan 22;15(2):543-558. doi: 10.1039/d3fo04633h.

Abstract

Astaxanthin is a carotenoid that is taken orally and has antitumor and anti-inflammatory properties. Our previous research demonstrated that astaxanthin alleviated skeletal muscle atrophy during sorafenib treatment in H22 tumor-bearing mice and altered the intestinal flora composition. However, the relationship between astaxanthin's amelioration of skeletal muscle atrophy in tumor-bearing mice and its ability to regulate intestinal flora is not clear. We used broad-spectrum antibiotics to create pseudo-sterile tumor-bearing mice, which we then used in fecal bacteria transplantation experiments. Our results indicate that the role of astaxanthin in ameliorating skeletal muscle atrophy during molecularly targeted therapy in mice with tumors is dependent on the intestinal flora. Astaxanthin substantially promoted the proliferation of , , and , altered the levels of metabolites in mouse serum, and primarily affected the amino acid metabolism of mice. Astaxanthin ameliorated skeletal muscle atrophy by promoting the activation of AKT/FOXO3a, which inhibited the expression of ubiquitination-degrading Fbx32 and MuRF1 and promoted myogenesis in skeletal muscle. Our study confirms that the intestinal flora is an important target for astaxanthin to combat skeletal muscle atrophy. Our research supports the use of astaxanthin as a nutritional supplement and intestinal microecological regulator for cancer patients.

摘要

虾青素是一种可口服的类胡萝卜素,具有抗肿瘤和抗炎作用。我们之前的研究表明,虾青素可减轻索拉非尼治疗荷瘤小鼠的骨骼肌萎缩,并改变肠道菌群组成。然而,虾青素改善荷瘤小鼠骨骼肌萎缩与其调节肠道菌群的能力之间的关系尚不清楚。我们使用广谱抗生素来构建假无菌荷瘤小鼠,并在这些小鼠中进行粪便细菌移植实验。我们的结果表明,虾青素在改善肿瘤荷瘤小鼠分子靶向治疗期间骨骼肌萎缩的作用依赖于肠道菌群。虾青素可显著促进 、 、 的增殖,改变小鼠血清中代谢物的水平,并主要影响小鼠的氨基酸代谢。虾青素通过促进 AKT/FOXO3a 的激活来改善骨骼肌萎缩,从而抑制泛素降解 Fbx32 和 MuRF1 的表达,并促进骨骼肌的肌生成。我们的研究证实,肠道菌群是虾青素对抗骨骼肌萎缩的一个重要靶点。我们的研究支持将虾青素作为一种营养补充剂和肠道微生态调节剂用于癌症患者。

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