Polygonati Rhizoma Prevents Glucocorticoid-Induced Growth Inhibition of Muscle via Promoting Muscle Angiogenesis Through Deoxycholic Acid

IF 9.1 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-06-16 DOI:10.1002/jcsm.13853

Shiyi Shi, Rui Li, Yanxu Han, Jiahao Xie, Shaoshuai Wang, Jie Liu, Fangyan Wan, Gaifeng Hou, Zuhong Liu, Xiaobo Sun, Bo Zuo, Zhihao Jia, Zhinan Mei, Tongxing Song

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Abstract

Background

Glucocorticoids are commonly used in clinical treatments but can cause muscle growth inhibition and weakness at high doses. The mechanisms and treatments for glucocorticoid-induced muscle growth inhibition remain poorly understood. This study aims to investigate the anti-atrophic effects of Polygonati Rhizoma (PR) and a mixture of low-dose fructose and glucose (MFG, an active component mimic in PR) on skeletal muscle.

Methods

Male C57BL/6 mice (3-week-old, n = 8) were gavaged with aqueous extract of PR (AEPR). MFG was used to gavage normal male C57BL/6 mice (3-week-old, n = 10) and male C57BL/6 mice with dexamethasone (DEX)-induced muscle growth inhibition (3-week-old, n = 7). After 2 weeks of gavage, the body weight and muscle mass of the mice were measured. Intestinal content was collected, the concentration of deoxycholic acid (DCA) was analysed and gut microbiota changes were assessed through 16S rRNA gene sequencing. Muscle angiogenesis was examined through the expression of vascular endothelial growth factors (VEGFs), focusing on the DCA-activated TGR5/cAMP/PKA/pCREB pathway.

Results

AEPR significantly increased the body weight (22.90 ± 0.90 vs. 21.83 ± 0.87 g, *p < 0.05) and grip strength (1.32 ± 0.11 vs. 1.04 ± 0.12 N, ***p < 0.001) of mice. MFG (0.5 g/kg body weight) also significantly elevated the body weight (21.44 ± 0.71 vs. 20.14 ± 0.82 g, **p < 0.01) and muscle mass (0.37 ± 0.018 vs. 0.33 ± 0.035 g, **p < 0.01) of mice. In the DEX group, MFG restored the DCA level (log₂[intensity]) in intestinal content (25.41 ± 1.64 vs. 22.69 ± 0.74, *p < 0.05) and increased the abundance of Collinsella aerofaciens as measured by DNA concentration (0.80 ± 0.64 vs. 0.24 ± 0.09 pg/μL, p = 0.096). Mechanistically, MFG upregulated VEGFs expression and promoted muscle angiogenesis via the TGR5/cAMP/PKA/pCREB pathway.

Conclusions

This study demonstrates that AEPR and its active component mimic MFG can promote muscle growth and MFG mitigates muscle growth inhibition by modulating gut microbiota and enhancing muscle angiogenesis. These findings suggest that fructose-containing treatments are novel strategies to address skeletal muscle dysfunction.

Abstract Image

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黄精通过脱氧胆酸促进肌肉血管生成，预防糖皮质激素诱导的肌肉生长抑制

糖皮质激素通常用于临床治疗，但高剂量会导致肌肉生长抑制和虚弱。糖皮质激素诱导的肌肉生长抑制的机制和治疗仍然知之甚少。本研究旨在探讨黄精（PR）和低剂量果糖和葡萄糖混合物（MFG， PR中的一种活性成分模拟物）对骨骼肌的抗萎缩作用。方法雄性C57BL/6小鼠（3周龄，n = 8）灌胃PR水提物（AEPR）。用MFG灌胃正常雄性C57BL/6小鼠（3周龄，n = 10）和雄性C57BL/6小鼠地塞米松（DEX）诱导的肌肉生长抑制（3周龄，n = 7）。灌胃2周后，测定小鼠体重和肌肉质量。收集肠道内容物，分析脱氧胆酸（DCA）浓度，并通过16S rRNA基因测序评估肠道菌群变化。通过血管内皮生长因子（vegf）的表达检测肌肉血管生成，重点关注dca激活的TGR5/cAMP/PKA/pCREB通路。结果AEPR显著提高小鼠体重（22.90±0.90比21.83±0.87 g, *p < 0.05）和握力（1.32±0.11比1.04±0.12 N, ***p < 0.001）。MFG （0.5 g/kg体重）也显著提高小鼠体重（21.44±0.71比20.14±0.82 g, **p < 0.01）和肌肉质量（0.37±0.018比0.33±0.035 g, **p < 0.01）。在DEX组中，MFG恢复了肠道内容物中DCA水平（log2[强度]）（25.41±1.64比22.69±0.74,*p < 0.05），并增加了气相Collinsella aerofaciens的丰度（0.80±0.64比0.24±0.09 pg/μL, p = 0.096）。在机制上，MFG通过TGR5/cAMP/PKA/pCREB途径上调vegf表达，促进肌肉血管生成。结论AEPR及其活性成分模拟MFG可通过调节肠道菌群和促进肌肉血管生成来促进肌肉生长，而MFG可减轻肌肉生长抑制。这些发现表明含果糖治疗是解决骨骼肌功能障碍的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.