Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model
Researches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of Spi...
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/24/5/896 |
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| author | Ji Eun Kim Ji Won Park Mi Ju Kang Hyeon Jun Choi Su Ji Bae Yusang Choi Young Ju Lee Sungbaek Seo Jin Tae Hong Dae Youn Hwang |
| author_facet | Ji Eun Kim Ji Won Park Mi Ju Kang Hyeon Jun Choi Su Ji Bae Yusang Choi Young Ju Lee Sungbaek Seo Jin Tae Hong Dae Youn Hwang |
| author_sort | Ji Eun Kim |
| collection | DOAJ |
| description | Researches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of SpiA on chronic constipation, we investigated alterations in the excretion parameters, histological structure, and cholinergic regulation of the enteric nerve in the colons of Institute of Cancer Research (ICR) mice with loperamide (Lop)-induced constipation after exposure to 20 mg/kg of SpiA. Decrease in the number, weight and water contents of stools in the Lop+Vehicle treated group significantly recovered after SpiA treatment, and alterations in the histological structure and transmission electron microscopy (TEM) images were improved in the Lop+SpiA treated group. Similar recovery effects were observed in the ability for mucin secretion and expression of the membrane water channel gene (aquaporin 8, AQP8). Furthermore, significant improvements were observed in the acetylcholinesterase (AChE) activity and acetylcholine receptors’ (AChRs) downstream signaling pathway after treatment of SpiA. The levels of gastrointestinal (GI) hormones including cholecystokinin (CCK) and gastrin were also remarkably enhanced in the Lop+SpiA treated group as compared to the Lop+Vehicle treated group. The expression of receptor tyrosine kinase (C-kit) and protein gene product 9.5 (PGP9.5) in Cajal and neural cells, as well as the phosphorylation of myosin light chain (MLC) in smooth muscle cells, were recovered after SpiA exposure. Taken together, the results of the present study provide the first strong evidence that SpiA improves chronic constipation through muscarinic cholinergic regulation of the enteric nerve in a Lop-induced constipation ICR mice model. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-14T11:13:42Z |
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| series | Molecules |
| spelling | doaj.art-36c291362d0d488388f7d725405a25f32022-12-21T23:04:09ZengMDPI AGMolecules1420-30492019-03-0124589610.3390/molecules24050896molecules24050896Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice ModelJi Eun Kim0Ji Won Park1Mi Ju Kang2Hyeon Jun Choi3Su Ji Bae4Yusang Choi5Young Ju Lee6Sungbaek Seo7Jin Tae Hong8Dae Youn Hwang9College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaCollege of Pharmacy, Chungbuk National University, Chungju 28160, KoreaCollege of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, KoreaResearches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of SpiA on chronic constipation, we investigated alterations in the excretion parameters, histological structure, and cholinergic regulation of the enteric nerve in the colons of Institute of Cancer Research (ICR) mice with loperamide (Lop)-induced constipation after exposure to 20 mg/kg of SpiA. Decrease in the number, weight and water contents of stools in the Lop+Vehicle treated group significantly recovered after SpiA treatment, and alterations in the histological structure and transmission electron microscopy (TEM) images were improved in the Lop+SpiA treated group. Similar recovery effects were observed in the ability for mucin secretion and expression of the membrane water channel gene (aquaporin 8, AQP8). Furthermore, significant improvements were observed in the acetylcholinesterase (AChE) activity and acetylcholine receptors’ (AChRs) downstream signaling pathway after treatment of SpiA. The levels of gastrointestinal (GI) hormones including cholecystokinin (CCK) and gastrin were also remarkably enhanced in the Lop+SpiA treated group as compared to the Lop+Vehicle treated group. The expression of receptor tyrosine kinase (C-kit) and protein gene product 9.5 (PGP9.5) in Cajal and neural cells, as well as the phosphorylation of myosin light chain (MLC) in smooth muscle cells, were recovered after SpiA exposure. Taken together, the results of the present study provide the first strong evidence that SpiA improves chronic constipation through muscarinic cholinergic regulation of the enteric nerve in a Lop-induced constipation ICR mice model.http://www.mdpi.com/1420-3049/24/5/896spicatoside Aconstipationaquaporinmucinmuscarinic acetylcholine receptorsgastrinC-kit |
| spellingShingle | Ji Eun Kim Ji Won Park Mi Ju Kang Hyeon Jun Choi Su Ji Bae Yusang Choi Young Ju Lee Sungbaek Seo Jin Tae Hong Dae Youn Hwang Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model Molecules spicatoside A constipation aquaporin mucin muscarinic acetylcholine receptors gastrin C-kit |
| title | Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model |
| title_full | Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model |
| title_fullStr | Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model |
| title_full_unstemmed | Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model |
| title_short | Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model |
| title_sort | laxative effect of spicatoside a by cholinergic regulation of enteric nerve in loperamide induced constipation icr mice model |
| topic | spicatoside A constipation aquaporin mucin muscarinic acetylcholine receptors gastrin C-kit |
| url | http://www.mdpi.com/1420-3049/24/5/896 |
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