Gao Yi, Deng Lan, Chen Yuanyuan, Qin Peiyou, Zhao Yuanyuan, Zhao Xiaoyan, Liu Wei, Wang Dan, Zhao Shuang
Institute of Agri-food Processing and Nutrition, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
Department of Stomatology, Beijing Xicheng District Health Care Hospital for Mothers and Children, Beijing, China.
Front Nutr. 2025 Jul 14;12:1635487. doi: 10.3389/fnut.2025.1635487. eCollection 2025.
Constipation is a prevalent gastrointestinal disorder demanding effective therapeutic strategies. This study investigated the therapeutic potential of polysaccharide (PCP-g), a novel galactoglucan, against sucralfate-induced constipation murine model, focusing on intestinal motility, fecal parameters, aquaporin signaling, and gut microbiota modulation.
PCP-g was purified from and its physicochemical properties were characterized. To evaluate the effects of PCP, the research utilized intestinal motility assays, fecal analysis, and fermentation. The role of Aquaporin 3 (AQP3) in constipation, especially regarding the PKA - phosphorylation mechanism, was investigated. The influence of PCP-g on PKA, phosphorylated PKA, AQP3, and tight junction proteins were examined at both the mRNA and protein levels.
PCP-g was identified as a homogeneous galactoglucan with a molecular weight of 7.49 × 10 kDa, characterized by a backbone consisting of 1→4-linked glucose (Glcp) and branches of mannose (Manp) and Glcp. The composition of PCP-g includes Glc, Gal, Man, L-Fuc, Rha, GlcA, and Ara, in a molar ratio of 1.00:0.16:0.13:0.01:0.006:0.005:0.006. The oral administration of PCP-g resulted in a significant reduction in constipation symptoms, as indicated by an increase in fecal water content, normalization of pellet formation, enhancement of total fecal mass, decreased latency to the first stool, and improved intestinal propulsion. Furthermore, PCP-g was found to elevate the production of short-chain fatty acids (SCFAs) while simultaneously reducing intestinal gas. Mechanistically, PCP-g suppressed the PKA-dependent phosphorylation of AQP3, leading to the downregulation of AQP3 overexpression and enhanced colonic epithelial permeability. Concurrently, PCP-g reduced the expression of tight junction proteins ZO-1 and Occludin, contributing to the increase in fecal water content.
PCP-g effectively alleviates constipation by enhancing intestinal motility and fecal hydration. It modulates the PKA-AQP3 signaling pathway to improve colonic water permeability and positively influences the gut environment through the generation of SCFAs. These findings suggest that PCP-g may serve as a promising therapeutic candidate for the treatment of constipation, operating through aquaporin signaling and the regulation of the gut environment. The study advocates for further clinical trials and highlights the potential of edible mushroom polysaccharides in the management of constipation.
便秘是一种常见的胃肠道疾病，需要有效的治疗策略。本研究调查了一种新型半乳葡聚糖——多糖（PCP - g）对硫糖铝诱导的便秘小鼠模型的治疗潜力，重点关注肠道蠕动、粪便参数、水通道蛋白信号传导和肠道微生物群调节。
从[具体来源]中纯化出PCP - g，并对其理化性质进行了表征。为了评估PCP的效果，该研究采用了肠道蠕动试验、粪便分析和[具体发酵方式]发酵。研究了水通道蛋白3（AQP3）在便秘中的作用，特别是关于PKA - 磷酸化机制。在mRNA和蛋白质水平上检测了PCP - g对PKA、磷酸化PKA、AQP3和紧密连接蛋白的影响。
PCP - g被鉴定为一种均一的半乳葡聚糖，分子量为7.49×10 kDa，其特征是由1→4连接的葡萄糖（Glcp）主链以及甘露糖（Manp）和Glcp分支组成。PCP - g的组成包括Glc、Gal、Man、L - Fuc、Rha、GlcA和Ara，摩尔比为1.00:0.16:0.13:0.01:0.006:0.005:0.006。口服PCP - g导致便秘症状显著减轻，表现为粪便含水量增加、粪便颗粒形成正常化、总粪便质量增加、首次排便潜伏期缩短以及肠道推进改善。此外，发现PCP - g可提高短链脂肪酸（SCFAs）的产生，同时减少肠道气体。从机制上讲，PCP - g抑制了AQP3的PKA依赖性磷酸化，导致AQP3过表达下调并增强结肠上皮通透性。同时，PCP - g降低了紧密连接蛋白ZO - 1和闭合蛋白的表达，有助于粪便含水量增加。
PCP - g通过增强肠道蠕动和粪便水合作用有效缓解便秘。它调节PKA - AQP3信号通路以改善结肠水通透性，并通过产生SCFAs对肠道环境产生积极影响。这些发现表明，PCP - g可能作为一种有前途的治疗便秘的候选药物，通过水通道蛋白信号传导和肠道环境调节发挥作用。该研究主张进一步开展临床试验，并强调了食用蘑菇多糖在便秘管理中的潜力。
