Guang-Jun Sun, Ming Li, Xiao-Yu Zhang, Jin-Shuang Liu, Ai-Zhen Lin, Qiong Cai
{"title":"魔芋寡糖通过激活5-HT4R/cAMP/PKA/p-CREB通路缓解小鼠便秘","authors":"Guang-Jun Sun, Ming Li, Xiao-Yu Zhang, Jin-Shuang Liu, Ai-Zhen Lin, Qiong Cai","doi":"10.1007/s11596-025-00102-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Konjac oligosaccharide (KOS), which is produced through the degradation of konjac glucomannan via enzymatic, chemical, or physical treatments, has been found to have laxative effects. The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.</p><p><strong>Methods: </strong>KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor (5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks. Following treatment, feces, blood, small intestine, colonic tissue, and intestinal contents were collected. Constipation-related parameters, gastrointestinal hormones, and Ca<sup>2+</sup> concentrations were evaluated. Histopathological changes were examined via hematoxylin and eosin staining. Immunofluorescence staining, Western blotting, and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. Isolated smooth muscle cells (SMCs) were treated with KOS and GR113808 (a 5-HT4R antagonist), morphologically observed under an inverted microscope, and identified by α-SMA immunofluorescence staining. Cell viability was assessed via CCK-8 assays. 5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.</p><p><strong>Results: </strong>KOS alleviated loperamide-induced constipation in mice. KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice. The protective effect of KOS was significantly diminished in 5-HT4R<sup>-/-</sup> mice. KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p><p><strong>Conclusion: </strong>KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Konjac Oligosaccharide Alleviates Constipation in Mice via 5-HT4R/cAMP/PKA/p-CREB Pathway Activation.\",\"authors\":\"Guang-Jun Sun, Ming Li, Xiao-Yu Zhang, Jin-Shuang Liu, Ai-Zhen Lin, Qiong Cai\",\"doi\":\"10.1007/s11596-025-00102-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Konjac oligosaccharide (KOS), which is produced through the degradation of konjac glucomannan via enzymatic, chemical, or physical treatments, has been found to have laxative effects. The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.</p><p><strong>Methods: </strong>KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor (5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks. Following treatment, feces, blood, small intestine, colonic tissue, and intestinal contents were collected. Constipation-related parameters, gastrointestinal hormones, and Ca<sup>2+</sup> concentrations were evaluated. Histopathological changes were examined via hematoxylin and eosin staining. Immunofluorescence staining, Western blotting, and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. Isolated smooth muscle cells (SMCs) were treated with KOS and GR113808 (a 5-HT4R antagonist), morphologically observed under an inverted microscope, and identified by α-SMA immunofluorescence staining. Cell viability was assessed via CCK-8 assays. 5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.</p><p><strong>Results: </strong>KOS alleviated loperamide-induced constipation in mice. KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice. The protective effect of KOS was significantly diminished in 5-HT4R<sup>-/-</sup> mice. KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p><p><strong>Conclusion: </strong>KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p>\",\"PeriodicalId\":10820,\"journal\":{\"name\":\"Current Medical Science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Medical Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11596-025-00102-7\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Medical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11596-025-00102-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Konjac Oligosaccharide Alleviates Constipation in Mice via 5-HT4R/cAMP/PKA/p-CREB Pathway Activation.
Background: Konjac oligosaccharide (KOS), which is produced through the degradation of konjac glucomannan via enzymatic, chemical, or physical treatments, has been found to have laxative effects. The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.
Methods: KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor (5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks. Following treatment, feces, blood, small intestine, colonic tissue, and intestinal contents were collected. Constipation-related parameters, gastrointestinal hormones, and Ca2+ concentrations were evaluated. Histopathological changes were examined via hematoxylin and eosin staining. Immunofluorescence staining, Western blotting, and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. Isolated smooth muscle cells (SMCs) were treated with KOS and GR113808 (a 5-HT4R antagonist), morphologically observed under an inverted microscope, and identified by α-SMA immunofluorescence staining. Cell viability was assessed via CCK-8 assays. 5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.
Results: KOS alleviated loperamide-induced constipation in mice. KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice. The protective effect of KOS was significantly diminished in 5-HT4R-/- mice. KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.
Conclusion: KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.
期刊介绍:
Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.