Zhang Yawei, Dong Yang, Sun Chenghong, Zhang Lufan, Zhang Yi, Wang Dan, Chen Qian, Yao Jingchun, Wu Yuzheng, Wang Tao
State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Microbiol. 2025 Jul 10;16:1596881. doi: 10.3389/fmicb.2025.1596881. eCollection 2025.
Shouhui Tongbian Capsule (SHTC) has been clinically applied to treat various types of constipation, including chemotherapy-induced constipation. However, the pharmacological mechanism by which it regulates intestinal peristalsis and treats constipation is unclear. In this study, we aimed to investigate the underlying mechanism of SHTC on chemotherapy-induced constipation through regulating of gut microbiota and PI3K/AKT/AQP3 signaling pathway.
Chemotherapy-induced constipation was induced with 5-Fluorouracil in C57BL/6 mice. SHTC was administrated with different dosages (100, 200, 400 mg/kg) for 12 days. The intestinal tissues were collected for the measurements of intestinal propulsion rate, time of first black stool, and expressions of colonic aquaporin. 16S rRNA sequencing, short-chain fatty acids (SCFAs) profiling, and fecal microbiota transplantation (FMT) were performed to confirm whether gut microbiota is a key target for SHTC. Finally, the expressions of proteins or genes related to PI3K/AKT/AQP3 pathway were detected.
SHTC markedly improved the pathological manifestations associated with constipation and restored the deregulated gut microbiota. The mice that were given fecal supernatant from SHTC-treated mice showed significant improvement in constipation symptoms. Additionally, SHTC increased the level of acetic acid and upregulated the expression of AQP3, with activation of PI3K/AKT. Furthermore, the blockade of PI3K reversed the beneficial effect of acetic acid on the expression of AQP3.
Our findings indicated that SHTC effectively relieved 5-FU-induced constipation in mice, mainly by regulating homeostasis of gut microbiota and activating PI3K/AKT/AQP3 pathway, making it a potential protective agent against chemotherapy-induced constipation.
首荟通便胶囊（SHTC）已在临床上用于治疗各种类型的便秘，包括化疗引起的便秘。然而，其调节肠道蠕动和治疗便秘的药理机制尚不清楚。在本研究中，我们旨在通过调节肠道微生物群和PI3K/AKT/AQP3信号通路来研究SHTC对化疗引起的便秘的潜在机制。
用5-氟尿嘧啶诱导C57BL/6小鼠发生化疗性便秘。给予不同剂量（100、200、400mg/kg）的SHTC，持续12天。收集肠道组织，测量肠道推进率、首次排黑便时间和结肠水通道蛋白的表达。进行16S rRNA测序、短链脂肪酸（SCFAs）分析和粪便微生物群移植（FMT），以确认肠道微生物群是否是SHTC的关键靶点。最后，检测与PI3K/AKT/AQP3通路相关的蛋白质或基因的表达。
SHTC显著改善了与便秘相关的病理表现，并恢复了失调的肠道微生物群。给予SHTC处理小鼠的粪便上清液的小鼠便秘症状有显著改善。此外，SHTC提高了乙酸水平，上调了AQP3的表达，并激活了PI3K/AKT。此外，PI3K的阻断逆转了乙酸对AQP3表达的有益作用。
我们的研究结果表明，SHTC能有效缓解5-FU诱导的小鼠便秘，主要是通过调节肠道微生物群的稳态和激活PI3K/AKT/AQP3通路，使其成为一种潜在的预防化疗引起便秘的保护剂。
