Zhou Rongrong, Liu Tingting, Qin You, Xie Jing, Zhang Shuihan, Xie Yi, Lao Jia, He Wei, Zeng Hongliang, Tang Xueyang, Tian Xuefei, Qin Yuhui
The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijng, China.
Front Pharmacol. 2025 Mar 10;16:1503785. doi: 10.3389/fphar.2025.1503785. eCollection 2025.
(PC) is an essential herbal medicine in China, known for improving muscle quality and enhancing physical function; its active ingredients are polysaccharides (PCPs). A previous study revealed the anti-atrophy effects of PCPs in cachectic mice. However, whether the effects of PCPs on anti-atrophy are associated with gut microenvironment remain elusive. This research endeavored to assess the medicinal efficacy of PCPs in alleviating muscle atrophy and fat lipolysis and explore the potential mechanisms. A cancer cachexia model was induced by male C57BL/6 mice bearing Lewis lung tumor cells and chemotherapy. The pharmacodynamics of PCPs (32 and 64 mg/kg/day) was investigated through measurements of tumor-free body weight, gastrocnemius muscle weight, soleus muscle weight, epididymal fat weight, tissue histology analysis, and pro-inflammatory cytokines. Immunohistochemistry and Western blotting assays were further used to confirm the effects of PCPs. 16S rRNA sequencing, LC-MS and GC-MS-based metabolomics were used to analyze the gut microbiota composition and metabolite alterations. Additionally, the agonist of free fatty acid receptor 2 (FFAR2)-a crucial short-chain fatty acid (SCFA) signaling molecule-was used to investigate the role of gut microbiota metabolites, specifically SCFAs, in the treatment of cancer cachexia, with comparisons to PCPs. This study demonstrated that PCPs significantly mitigated body weight loss, restored muscle fiber atrophy and mitochondrial disorder, alleviated adipose tissue wasting, strengthened the intestinal barrier integrity, and decreased the intestinal inflammation in chemotherapy-induced cachexia. Furthermore, the reversal of specific bacterial taxa including , , , , , , , , , , , , and , along with alterations in metabolites such as amino acids (AAs), eicosanoids, lactic acid and (SCFAs), contributed to the therapeutic effects of PCPs. Our findings suggest that PCPs can be used as prebiotic drugs targeting the microbiome-metabolomics axis in cancer patients undergoing chemotherapy.
党参是中国一种重要的草药，以改善肌肉质量和增强身体机能而闻名；其活性成分是多糖（PCPs）。先前的一项研究揭示了PCPs对恶病质小鼠的抗萎缩作用。然而，PCPs的抗萎缩作用是否与肠道微环境有关仍不清楚。本研究旨在评估PCPs在减轻肌肉萎缩和脂肪脂解方面的药效，并探索其潜在机制。通过雄性C57BL/6小鼠接种Lewis肺癌细胞并进行化疗诱导建立癌症恶病质模型。通过测量无瘤体重、腓肠肌重量、比目鱼肌重量、附睾脂肪重量、组织组织学分析和促炎细胞因子来研究PCPs（32和64mg/kg/天）的药效学。进一步使用免疫组织化学和蛋白质印迹分析来确认PCPs的作用。基于16S rRNA测序、液相色谱-质谱联用和气相色谱-质谱联用的代谢组学用于分析肠道微生物群组成和代谢物变化。此外，使用游离脂肪酸受体2（FFAR2）的激动剂——一种关键的短链脂肪酸（SCFA）信号分子——来研究肠道微生物群代谢物，特别是SCFAs，在癌症恶病质治疗中的作用，并与PCPs进行比较。本研究表明，PCPs显著减轻体重减轻，恢复肌肉纤维萎缩和线粒体紊乱，减轻脂肪组织消耗，加强肠道屏障完整性，并减少化疗诱导的恶病质中的肠道炎症。此外，特定细菌类群的逆转，包括 、 、 、 、 、 、 、 、 、 、 、 、 和 ，以及氨基酸（AAs）、类二十烷酸、乳酸和（SCFAs）等代谢物的变化，促成了PCPs的治疗效果。我们的研究结果表明，PCPs可作为针对化疗癌症患者微生物组-代谢组学轴的益生元药物。
