Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway
ObjectiveShouhui 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...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1596881/full |
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| author | Yawei Zhang Yawei Zhang Yang Dong Yang Dong Chenghong Sun Lufan Zhang Lufan Zhang Yi Zhang Yi Zhang Dan Wang Dan Wang Dan Wang Qian Chen Qian Chen Qian Chen Jingchun Yao Yuzheng Wu Yuzheng Wu Yuzheng Wu Tao Wang Tao Wang |
| author_facet | Yawei Zhang Yawei Zhang Yang Dong Yang Dong Chenghong Sun Lufan Zhang Lufan Zhang Yi Zhang Yi Zhang Dan Wang Dan Wang Dan Wang Qian Chen Qian Chen Qian Chen Jingchun Yao Yuzheng Wu Yuzheng Wu Yuzheng Wu Tao Wang Tao Wang |
| author_sort | Yawei Zhang |
| collection | DOAJ |
| description | ObjectiveShouhui 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.MethodsChemotherapy-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.ResultsSHTC 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-d88f1bfabe9e4177bfbc92fb8a7061b4 |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-d88f1bfabe9e4177bfbc92fb8a7061b42025-08-20T02:36:04ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.15968811596881Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathwayYawei Zhang0Yawei Zhang1Yang Dong2Yang Dong3Chenghong Sun4Lufan Zhang5Lufan Zhang6Yi Zhang7Yi Zhang8Dan Wang9Dan Wang10Dan Wang11Qian Chen12Qian Chen13Qian Chen14Jingchun Yao15Yuzheng Wu16Yuzheng Wu17Yuzheng Wu18Tao Wang19Tao Wang20State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, ChinaState Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, ChinaState Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaObjectiveShouhui 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.MethodsChemotherapy-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.ResultsSHTC 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1596881/fullShouhui Tongbian Capsule (SHTC)5-fluorouracil (5-FU)chemotherapy-induced constipation (CIC)gut microbiotafecal microbiota transplantation (FMT) |
| spellingShingle | Yawei Zhang Yawei Zhang Yang Dong Yang Dong Chenghong Sun Lufan Zhang Lufan Zhang Yi Zhang Yi Zhang Dan Wang Dan Wang Dan Wang Qian Chen Qian Chen Qian Chen Jingchun Yao Yuzheng Wu Yuzheng Wu Yuzheng Wu Tao Wang Tao Wang Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway Frontiers in Microbiology Shouhui Tongbian Capsule (SHTC) 5-fluorouracil (5-FU) chemotherapy-induced constipation (CIC) gut microbiota fecal microbiota transplantation (FMT) |
| title | Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway |
| title_full | Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway |
| title_fullStr | Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway |
| title_full_unstemmed | Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway |
| title_short | Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway |
| title_sort | shouhui tongbian capsule ameliorates 5 fluorouracil induced constipation in mice by modulating gut microbiota and activating pi3k akt aqp3 signaling pathway |
| topic | Shouhui Tongbian Capsule (SHTC) 5-fluorouracil (5-FU) chemotherapy-induced constipation (CIC) gut microbiota fecal microbiota transplantation (FMT) |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1596881/full |
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