{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:14:20Z","timestamp":1790864060254,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Senna and its main components sennosides are well-known effective laxative drugs and are used in the treatment of intestinal constipation in the world. Their potential side effects have attracted more attention in clinics but have little scientific justification. In this study, senna extract (SE), sennosides (SS), and sennoside A (SA) were prepared and used to generate diarrhea rats. The diarrhea rats were investigated with behaviors, clinical signs, organ index, pathological examination, and gene expression on multiple aquaporins (Aqps) including Aqp1, Aqp2, Aqp3, Aqp4, Aqp5, Aqp6, Aqp7, Aqp8, Aqp9, and Aqp11. Using qRT-PCR, the Aqp expression profiles were constructed for six organs including colon, kidney, liver, spleen, lung, and stomach. The Aqp alteration profiles were characterized and was performed with Principle Component Analysis (PCA). The SE treatments on the rats resulted in a significant body weight loss (p &lt; 0.001), significant increases (p &lt; 0.001) on the kidney index (27.72%) and liver index (42.55%), and distinguished changes with up-regulation on Aqps expressions in the kidneys and livers. The SS treatments showed prominent laxative actions and down regulation on Aqps expression in the colons. The study results indicated that the SE had more influence\/toxicity on the kidneys and livers. The SS showed more powerful actions on the colons. We suggest that the caution should be particularly exercised in the patients with kidney and liver diseases when chronic using senna-based products.<\/jats:p>","DOI":"10.3390\/ijms19103210","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T10:22:54Z","timestamp":1539771774000},"page":"3210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Aquaporins Alteration Profiles Revealed Different Actions of Senna, Sennosides, and Sennoside A in Diarrhea-Rats"],"prefix":"10.3390","volume":"19","author":[{"given":"Yixin","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejing","family":"Qu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boling","family":"Qiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 TaiBai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0731-7085(02)00208-X","article-title":"Validated HPLC method for determination of sennosides A and B in senna tablets","volume":"29","author":"Sun","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1046\/j.1365-2036.1999.00468.x","article-title":"Anthranoid laxatives and their potential carcinogenic effects","volume":"13","author":"Karrenbeld","year":"1999","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jpedsurg.2018.01.002","article-title":"Are Senna based laxatives safe when used as long term treatment for constipation in children?","volume":"53","author":"Vilanovasanchez","year":"2018","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","first-page":"835","article-title":"Laxative anthraquinone contents in fresh and cooked Senna siamea leaves","volume":"40","author":"Sakulpanich","year":"2009","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1513\/pats.200510-109JH","article-title":"The Aquaporin Water Channels","volume":"3","author":"Agre","year":"2006","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.mam.2012.04.003","article-title":"On the definition, nomenclature and classification of water channel proteins (aquaporins and relatives)","volume":"33","author":"Benga","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/BF02480636","article-title":"Aquaporin water channels in mammals","volume":"1","author":"Ishibashi","year":"1997","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.mam.2012.03.001","article-title":"Water channel proteins in the gastrointestinal tract","volume":"33","author":"Laforenza","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ikarashi, N., Kon, R., and Sugiyama, K. (2016). Aquaporins in the Colon as a New Therapeutic Target in Diarrhea and Constipation. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071172"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.fitote.2012.05.015","article-title":"Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model","volume":"83","author":"Zhang","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cui, Z., Zhuang, C., and Jiang, Z. (2016). Expression, distribution and role of aquaporin water channels in human and animal stomach and intestines. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091399"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-94-024-1057-0_9","article-title":"Aquaporins in Urinary System","volume":"969","author":"Li","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/toxsci\/kfv055","article-title":"Morphine-Induced Constipation Develops with Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion","volume":"145","author":"Kon","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/sj.gene.6364190","article-title":"Real-time RT-PCR normalisation; strategies and considerations","volume":"6","author":"Huggett","year":"2005","journal-title":"Genes Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1080\/15563650701682097","article-title":"Portal vein thrombosis related to Cassia angustifolia","volume":"46","author":"Soyuncu","year":"2008","journal-title":"Clin. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1074\/jbc.271.9.4577","article-title":"The Mercurial Insensitive Water Channel (AQP-4) Forms Orthogonal Arrays in Stably Transfected Chinese Hamster Ovary Cells","volume":"271","author":"Yang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22907","DOI":"10.1074\/jbc.270.39.22907","article-title":"cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units","volume":"270","author":"Yang","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C985","DOI":"10.1152\/ajpcell.00033.2013","article-title":"Relative CO2\/NH3 selectivities of mammalian aquaporins 0-9","volume":"304","author":"Geyer","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1462-5822.2006.00773.x","article-title":"Aquaporins contribute to diarrhoea caused by attaching and effacing bacterial pathogens","volume":"9","author":"Guttman","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"G463","DOI":"10.1152\/ajpgi.2000.279.2.G463","article-title":"Colon water transport in transgenic mice lacking aquaporin-4 water channels","volume":"279","author":"Wang","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/mpat.2002.0502","article-title":"Positive and negative regulation of water channel aquaporins in human small intestine by cholera toxin","volume":"32","author":"Hamabata","year":"2002","journal-title":"Microb. Pathog."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00441-004-0932-4","article-title":"Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn\u2019s disease and infectious colitis","volume":"318","author":"Hardin","year":"2004","journal-title":"Cell Tissue Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.lfs.2007.04.036","article-title":"Downregulation in aquaporin 4 and aquaporin 8 expression of the colon associated with the induction of allergic diarrhea in a mouse model of food allergy","volume":"81","author":"Yamamoto","year":"2007","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1113\/jphysiol.2001.020180","article-title":"Localization of aquaporin-5 in sweat glands and functional analysis using knockout mice","volume":"541","author":"Song","year":"2010","journal-title":"J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41288","DOI":"10.1074\/jbc.M107257200","article-title":"Aquaporin-5 dependent fluid secretion in airway submucosal glands","volume":"276","author":"Song","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1073\/pnas.0813231106","article-title":"Relative CO2\/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00018-016-2142-0","article-title":"Aquaporin-5: From structure to function and dysfunction in cancer","volume":"73","author":"Direito","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6793-9-18","article-title":"Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine","volume":"9","author":"Laforenza","year":"2009","journal-title":"BMC Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1073\/pnas.0409232102","article-title":"Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution","volume":"102","author":"Liu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00424-004-1245-x","article-title":"Aquaporin 6 is permeable to glycerol and urea","volume":"448","author":"Holm","year":"2004","journal-title":"Pflugers Arch."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"39873","DOI":"10.1074\/jbc.M207008200","article-title":"Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63","volume":"277","author":"Ikeda","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/CEG.S70119","article-title":"Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease","volume":"2015","author":"Ricanek","year":"2015","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/BC20040090","article-title":"Expression and immunolocalization of aquaporin-7 in rat gastrointestinal tract","volume":"97","author":"Laforenza","year":"2005","journal-title":"Biol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"F1047","DOI":"10.1152\/ajprenal.0158.2001","article-title":"Immunolocalization of aquaporin-8 in rat kidney, gastrointestinal tract, testis, and airways","volume":"281","author":"Elkjaer","year":"2001","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6793-1-1","article-title":"Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors","volume":"1","author":"Fischer","year":"2001","journal-title":"BMC Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1093\/jn\/135.10.2329","article-title":"Aquaporin-8 Is Involved in Water Transport in Isolated Superficial Colonocytes from Rat Proximal Colon","volume":"135","author":"Laforenza","year":"2005","journal-title":"J. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbrc.2013.11.067","article-title":"Aquaporin 3 and 8 are down-regulated in TNBS-induced rat colitis","volume":"443","author":"Zhao","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G887","DOI":"10.1152\/ajpgi.00286.2011","article-title":"The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages","volume":"301","author":"Ikarashi","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11418-018-1174-1","article-title":"Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon","volume":"72","author":"Kon","year":"2018","journal-title":"J. Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1006\/bbrc.2000.3638","article-title":"Localization of Aquaporin-7 in Rat and Mouse Kidney Using RT-PCR, Immunoblotting, and Immunocytochemistry","volume":"277","author":"Nejsum","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000020676","article-title":"Cellular localization of aquaporin 7 in the rat kidney","volume":"8","author":"Ishibashi","year":"2000","journal-title":"Exp. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.bbadis.2017.03.012","article-title":"Aquaporin-3 deletion in mice results in renal collecting duct abnormalities and worsens ischemia-reperfusion injury","volume":"1863","author":"Lei","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.bbamem.2006.04.002","article-title":"Physiological roles of AQP7 in the kidney: Lessons from AQP7 knockout mice","volume":"1758","author":"Sohara","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17801","DOI":"10.1073\/pnas.0406230101","article-title":"Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue","volume":"101","author":"Maeda","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1006\/bbrc.2000.3505","article-title":"Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain","volume":"276","author":"Elkjaer","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbrc.2016.01.153","article-title":"Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells","volume":"471","author":"Watanabe","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.bbrc.2018.04.108","article-title":"Sennoside A protects mitochondrial structure and function to improve high-fat diet-induced hepatic steatosis by targeting VDAC1","volume":"500","author":"Le","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","unstructured":"State Pharmacopoeia Commission (2015). Pharmacopoeia of the People\u2019s Republic of China, Chinese Pharmacopoeia Commission."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D805","DOI":"10.1093\/nar\/gkl767","article-title":"qPrimerDepot: A primer database for quantitative real time PCR","volume":"35","author":"Cui","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394Ct Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:26:15Z","timestamp":1760196375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,17]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19103210"],"URL":"https:\/\/doi.org\/10.3390\/ijms19103210","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,17]]}}}