Abstract
Rhubarb, the rhizome and root of Rheum palmatum L. from the Polygonaceae family, is a globally important medicinal plant, especially in eastern Asia. It has been indicated for enteritis, gastritis, constipation, and diarrhea in Persian medicine. Several pharmacological investigations in previous decades have been conducted on anthraquinones of rhubarb responsible for diarrheagenic activities and rhubarb tannins initiating anti-diarrheagenic effects. Aloe-emodin, chrysophanol, emodin, physcion, rhein, and their glycosides are major rhubarb anthraquinones. Moreover, catechin, catechin gallate, catechin-glucopyranoside, gallic acid, galloyl glucose, carboxyl-chrysophanol-O- glucose, coumaroyl-O-galloyl-glucose, di-O-galloyl-glucose, glucopyranosyl-galloyl-glucose, and di-, tri-, tetra-, and pentamer of catechin units are major rhubarb tannins. In this paper, a review of relevant pharmacological studies on rhubarb tannins and anthraquinones published in PubMed and Scopus databases is performed. In addition, the hub genes and common targets of rhubarb anthraquinones and tannins were investigated using gene expression databases. Thirty common differentially expressed target genes were identified. According to the survey, the pharmacology of rhubarb is linked to aquaporin expression and maintained inflammatory responses in the intestinal environment, where anthraquinones and tannins play as positive and negative regulators. Furthermore, their opposing effects on intestinal motility, fluid absorption, and water/electrolyte secretion are explained. Anthraquinones inhibit the Na+/K+ATPase pump while stimulating cystic fibrosis transmembrane conductance regulator (CFTR) and Ca2+-activated Cl− channels (CACC). Tannins reduce fluid secretion and smooth muscle contraction by inhibiting CACC and CFTR. This linkage opens new aspects for rhubarb pharmacology, its diarrheagenic/anti-diarrheagenic effects, and philosophical concepts of Hot and Cold temperaments in traditional medicine.
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Abbreviations
- AQP:
-
Aquaporin
- ASC:
-
Apoptosis-associated speck-like protein containing a CARD domain
- CACC:
-
Calcium-activated chloride channel
- CFTR:
-
Cystic fibrosis transmembrane conductance regulator
- COX2:
-
Cyclooxygenase-2
- CREB:
-
CAMP response element-binding protein
- GEO:
-
Gene expression omnibus
- 5HT:
-
5-Hydroxytryptamine
- ICC:
-
Interstitial cells of Cajal
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- MC:
-
Melanosis coli
- NLRP3:
-
Nucleotide-binding oligomerization domain-like receptors 3
- PLAU:
-
Plasminogen activator, urokinase
- PKA:
-
Protein kinase A
- PG:
-
Prostaglandin
- SigA:
-
Secretory immunoglobin A
- TICAM1:
-
Toll-like receptor adaptor molecule 1
- TPM:
-
Traditional Persian medicine
References
Al Rahim M, Nakajima A, Saigusa D, Tetsu N, Maruyama Y, Shibuya M, Yamakoshi H, Tomioka Y, Iwabuchi Y, Ohizumi Y, Yamakuni T (2009) 4’-Demethylnobiletin, a bioactive metabolite of nobiletin enhancing PKA/ERK/CREB signaling, rescues learning impairment associated with NMDA receptor antagonism via stimulation of the ERK cascade. Biochemistry 48:7713–7721. https://doi.org/10.1021/bi901088w
Alexopoulou L, Kontoyiannis D (2005) Intestinal epithelial barrier and mucosal immunity. Cell Mol Life Sci 62:1349. https://doi.org/10.1007/s00018-005-5039-x
Ali S, Watson MS, Osborne RH (2004) The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine. Auton Autacoid Pharmacol 24:103–105. https://doi.org/10.1111/j.1474-8673.2004.00321.x
Amberg GC, Koh SD, Hatton WJ, Murray KJ, Monaghan K, Horowitz B, Sanders KM (2002) Contribution of Kv4 channels toward the A-type potassium current in murine colonic myocytes. Physiol J 544:403–415. https://doi.org/10.1113/jphysiol.2002.025163
Anderson KJ, Cormier RT, Scott PM (2019) Role of ion channels in gastrointestinal cancer. World J Gastroenterol 25:5732–5772. https://doi.org/10.3748/wjg.v25.i38.5732
Arcidiacono T, Mingione A, Macrina L, Pivari F, Soldati L, Vezzoli G (2014) Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies. Am J Nephrol 40:499–506. https://doi.org/10.1159/000369833
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29. https://doi.org/10.1038/75556
Atianand MK, Harton JA (2011) Uncoupling of Pyrin-only protein 2 (POP2)-mediated dual regulation of NF-κB and the inflammasome. J Biol Chem 286:40536–40547. https://doi.org/10.1074/jbc.M111.274290
Bao JQ, Li F, Zhang WS, Xu YB, Liu Q, Wang X, Zhao YL, Wang CH (2008) Effect of total anthraquinone in rheum on aquaporin 2 expression in rat distal colon. Zhongguo Zhong Yao Za Zhi 33:1732–1735
Barbosa DM, Fahlbusch P, Herzfeld de Wiza D, Jacob S, Kettel U, Al-Hasani H, Krüger M, Ouwens DM, Hartwig S, Lehr S, Kotzka J, Knebel B (2020) Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis. Sci Rep 10:4888. https://doi.org/10.1038/s41598-020-61886-3
Barnes J, Anderson LA, Phillipson JD (2007) Herbal medicines. Pharmaceutical Press, London
Boyd A, Aragon IV, Abou Saleh L, Southers D, Richter W (2021) The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice. Biochem J 478:1891–1906. https://doi.org/10.1042/BCJ20210212
Brost S, Koschny R, Sykora J, Stremmel W, Lasitschka F, Walczak H, Ganten TM (2010) Differential expression of the TRAIL/TRAIL-receptor system in patients with inflammatory bowel disease. Pathol Res Pract 206:43–50. https://doi.org/10.1016/j.prp.2009.09.005
Burkitt RW (1921) The use of rhubarb in acute bacillary dysentery. Lancet 198:254–255
Cai L, Li YP, Wei ZX, Li XL, Jiang XR (2020) Effects of dietary gallic acid on growth performance, diarrhea incidence, intestinal morphology, plasma antioxidant indices, and immune response in weaned piglets. Anim Feed Sci Technol 261:114391
Cao YJ, Pu ZJ, Tang YP, Shen J, Chen YY, Kang A, Zhou GS, Duan JA (2017) Advances in bio-active constituents, pharmacology and clinical applications of rhubarb. Chin Med 12:36. https://doi.org/10.1186/s13020-017-0158-5
Chang J, Zhang L, Gu X, Liu L, Li Z, Miao G, Liu X, Liu P, Xue H, Liu C, Fu Q (2018) The rhubarb total free anthraquinone oral colon-specific drug delivery granules: comparative pharmacokinetics study with rhubarb by UPLC-MS/MS after oral administration. J Drug Deliv Sci Technol 43:415–422
Chao G, Zhang S (2017) Aquaporins 1, 3 and 8 expression in irritable bowel syndrome rats’ colon via NF-κB pathway. Oncotarget 8:47175–47183. https://doi.org/10.18632/oncotarget.17565
Chen JY, Pan F, Zhang T, Xia J, Li YJ (2011) Experimental study on the molecular mechanism of anthraquinone cathartics in inducing melanosis coli. Chin J Integr Med 17:525–530. https://doi.org/10.1007/s11655-011-0786-z
Cheng L, Chen Q, Pi R, Chen J (2021) A research update on the therapeutic potential of rhein and its derivatives. Eur J Pharmacol 899:173908. https://doi.org/10.1016/j.ejphar.2021.173908
Cheng Y, Hall TR, Xu X, Yung I, Souza D, Zheng J, Schiele F, Hoffmann M, Mbow ML, Garnett JP, Li J (2022) Targeting uPA-uPAR interaction to improve intestinal epithelial barrier integrity in inflammatory bowel disease. EBioMedicine 75:103758. https://doi.org/10.1016/j.ebiom.2021.103758
Choi YJ, Im E, Chung HK, Pothoulakis C, Rhee SH (2010) TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells. Biol Chem 285:37570–37578. https://doi.org/10.1074/jbc.M110.158394
Cires MJ, Wong X, Carrasco-Pozo C, Gotteland M (2017) The gastrointestinal tract as a key target organ for the health-promoting effects of dietary proanthocyanidins. Front Nutr 3:57. https://doi.org/10.3389/fnut.2016.00057
Clementi EM, Misiti F (2010) Potential health benefits of rhubarb. In: Ronald Ross W, Victor RP (eds) Bioactive foods in promoting health. Academic Press, San Diego, pp 407–423
Conley CA (2001) Leiomodin and tropomodulin in smooth muscle. Am J Physiol Cell Physiol 280:C1645–C1656. https://doi.org/10.1152/ajpcell.2001.280.6.C1645
Cui HX, Zhang LS, Luo Y, Yuan K, Huang ZY, Guo Y (2019) A purified anthraquinone-glycoside preparation from rhubarb ameliorates type 2 diabetes mellitus by modulating the gut microbiota and reducing inflammation. Front Microbiol 10:1423. https://doi.org/10.3389/fmicb.2019.01423
da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. https://doi.org/10.1038/nprot.2008.211
Davis S, Meltzer PS (2007) GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor. Bioinformatics 23:1846–1847. https://doi.org/10.1093/bioinformatics/btm254
Degerman E, Rauch U, Göransson O, Lindberg S, Hultgårdh A, Magnusson M (2011) Identification of new signaling components in the sensory epithelium of human saccule. Front Neurol 2:48. https://doi.org/10.3389/fneur.2011.00048
Deng C, Deng B, Jia L, Tan H, Zhang P, Liu S, Zhang Y, Song A, Pan L (2017) preventive effects of a Chinese herbal formula, Shengjiang Xiexin decoction, on irinotecan-induced delayed-onset diarrhea in rats. Evid Based Complement Altern Med 2017:7350251. https://doi.org/10.1155/2017/7350251
Dietz BM, Hajirahimkhan A, Dunlap TL, Bolton JL (2016) botanicals and their bioactive phytochemicals for women’s health. Pharmacol Rev 68:1026–1073. https://doi.org/10.1124/pr.115.010843
Ding M, Ni W (2004) Separation of tannins in Rhubarb and its analysis by high performance liquid chromatography-mass spectrometry. Se Pu 22:605–608
Duong van Huyen JP, Cheval L, Bloch-Faure M, Belair MF, Heudes D, Bruneval P, Doucet A (2008) GDF15 triggers homeostatic proliferation of acid-secreting collecting duct cells. J Am Soc Nephrol 19:1965–1974. https://doi.org/10.1681/ASN.2007070781
Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30:207–210. https://doi.org/10.1093/nar/30.1.207
Esser D, Geleijnse JM, Matualatupauw JC, Dower JI, Kromhout D, Hollman PCH, Afman LA (2018) Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: a randomised double-blind, placebo-controlled, crossover trial. PLoS ONE 13:e0194229. https://doi.org/10.1371/journal.pone.0194229
Fan XS, Wu HY, Yu HP, Zhou Q, Zhang YF, Huang Q (2010) Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with beta-catenin. Int J Colorectal Dis 25:583–590. https://doi.org/10.1007/s00384-010-0903-z
Feng TS, Yuan ZY, Yang RQ, Zhao S, Lei F, Xiao XY, Xing DM, Wang WH, Ding Y, Du LJ (2013) Purgative components in rhubarbs: adrenergic receptor inhibitors linked with glucose carriers. Fitoterapia 91:236–246. https://doi.org/10.1016/j.fitote.2013.09.020
Gamboa HE, Sood M (2019) Pediatric intestinal pseudo-obstruction in the era of genetic sequencing. Curr Gastroenterol Rep 21:70. https://doi.org/10.1007/s11894-019-0737-y
Ghanbarzadeh Z, Hemmati S, Mohagheghzadeh A (2022) Humanizing plant-derived snakins and their encrypted antimicrobial peptides. Biochimie 199:92–111. https://doi.org/10.1016/j.biochi.2022.04.011
Gharashi A (2008) Al-shamel fi-alsanaat-altebyah. Iran University of Medical Sciences Publication, Tehran
Girard M, Bee G (2020) Invited review: Tannins as a potential alternative to antibiotics to prevent coliform diarrhea in weaned pigs. Animal 14:95–107. https://doi.org/10.1017/S1751731119002143
Girish N, Liu CY, Gadeock S, Gomez ML, Huang Y, Sharifkhodaei Z, Washington MK, Polk DB (2021) Persistence of Lgr5+ colonic epithelial stem cells in mouse models of inflammatory bowel disease. Am J Physiol Gastrointest 321:G308–G324. https://doi.org/10.1152/ajpgi.00248.2020
Gong XH, Li Y, Zhang RQ, Xie XF, Peng C, Li YX (2015) The synergism mechanism of Rhubarb anthraquinones on constipation elucidated by comparative pharmacokinetics of Rhubarb extract between normal and diseased rats. Eur J Drug Metab Pharmacokinet 40:379–388. https://doi.org/10.1007/s13318-014-0216-7
Guo Y, Feng P (2012) OX2R activation induces PKC-mediated ERK and CREB phosphorylation. Exp Cell Res 318:2004–2013. https://doi.org/10.1016/j.yexcr.2012.04.015
Haneda M, Hayashi S, Matsumoto T, Hashimoto S, Takayama K, Chinzei N, Kihara S, Takeuchi K, Nishida K, Kuroda R (2018) Depletion of aquaporin 1 decreased ADAMTS 4 expression in human chondrocytes. Mol Med Rep 17:4874–4882. https://doi.org/10.3892/mmr.2018.8545
Hatane T, Yoshida E, Kawano J, Sugiki M, Onitsuka T, Maruyama M (1998) Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast. Biochem Biophys Acta 1403:189–198. https://doi.org/10.1016/s0167-4889(98)00041-x
Hemmati S, Schneider B, Schmidt TJ, Federolf K, Alfermann AW, Fuss E (2007) Justicidin B 7-hydroxylase, a cytochrome P450 monooxygenase from cell cultures of Linum perenne Himmelszelt involved in the biosynthesis of diphyllin. Phytochemistry 68:2736–2743. https://doi.org/10.1016/j.phytochem.2007.10.025
Heymann JB, Engel A (1999) Aquaporins: phylogeny, structure, and physiology of water channels. News Physiol Sci 14:187–193
Hoblyn FP (1841) Burnt rhubarb in diarrhoea. Lancet 35:790
Hohmann I, Bill RM, Kayingo I, Prior BA (2000) Microbial MIP channels. Trends Microbiol 8:33–38. https://doi.org/10.1016/s0966-842x(99)01645-5
Hu B, Zhang H, Meng X, Wang F, Wang P (2014) Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. J Ethnopharmacol 153:846–853. https://doi.org/10.1016/j.jep.2014.03.059
Huang WS, Chin CC, Chen CN, Kuo YH, Chen TC, Yu HR, Tung SY, Shen CH, Hsieh YY, Guo SE, Shi CS, Liu TJ, Kuo HC (2012) Stromal cell-derived factor-1/CXC receptor 4 and β1 integrin interaction regulates urokinase-type plasminogen activator expression in human colorectal cancer cells. J Cell Physiol 227:1114–1122. https://doi.org/10.1002/jcp.22831
Huang Z, Xu Y, Wang Q, Gao X (2019) Metabolism and mutual biotransformations of anthraquinones and anthrones in rhubarb by human intestinal flora using UPLC-Q-TOF/MS. J Chromatogr B Analyt Technol Biomed Life Sci 1104:59–66. https://doi.org/10.1016/j.jchromb.2018.10.008
Huo X, Liu S, Li Y, Wei H, Gao J, Yan Y, Zhang G, Liu M (2021) Analysis of synonymous codon usage of transcriptome database in Rheum palmatum. PeerJ 9:e10450. https://doi.org/10.7717/peerj.10450
Iguchi G, Chrysovergis K, Lee SH, Baek SJ, Langenbach R, Eling TE (2009) A reciprocal relationship exists between non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) and cyclooxygenase-2. Cancer Lett 282:152–158. https://doi.org/10.1016/j.canlet.2009.03.006
Ishikawa K, Sugimoto S, Oda M, Fujii M, Takahashi S, Ohta Y, Takano A, Ishimaru K, Matano M, Yoshida K, Hanyu H, Toshimitsu K, Sawada K, Shimokawa M, Saito M, Kawasaki K, Ishii R, Taniguchi K, Imamura T, Kanai T, Sato T et al (2022) Identification of quiescent LGR5+ stem cells in the human colon. Gastroenterology 163:1391-1406.e24. https://doi.org/10.1053/j.gastro.2022.07.081
Ishimaru K, Satake M, Shimomura K (1990) Production of (+)-catechin in root and cell suspension cultures of Rheum palmatum L. Plant Tissue Cult Lett 7:159–163
Ito J, Nogami M, Morita Y, Sakaguchi K, Komada H, Hirota Y, Sugawara K, Tamori Y, Zeng F, Murakami T, Ogawa W (2021) Dose-dependent accumulation of glucose in the intestinal wall and lumen induced by metformin as revealed by 18 F-labelled fluorodeoxyglucose positron emission tomography-MRI. Diabetes Obes Metab 23:692–699. https://doi.org/10.1111/dom.14262
Iwamoto J, Takahashi K, Mizokami Y, Otsubo T, Miura S, Narasaka T, Takeyama H, Omata T, Shimokoube K, Matsuoka T (2003) Expression of urokinase-type plasminogen activator and its receptor in gastric fibroblasts and effects of nonsteroidal antiinflammatory drugs and prostaglandin. Dig Dis Sci 48:2247–2256. https://doi.org/10.1023/b:ddas.0000007859.10680.b1
Iwaya M, Ota H, Nakajima T, Uehara T, Riddell R, Conner J (2021) Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma. BMC Cancer 21:119. https://doi.org/10.1186/s12885-021-07835-3
Izhaki I (2002) Emodin - a secondary metabolite with multiple ecological functions in higher plants. New Phytol 155:205–217
Jaswal S, Anand V, Kumar S, Bathla S, Dang AK, Kaushik JK, Mohanty AK (2020) In-depth proteome analysis of more than 12,500 proteins in buffalo mammary epithelial cell line identifies protein signatures for active proliferation and lactation. Sci Rep 10:4834. https://doi.org/10.1038/s41598-020-61521-1
Jing W, Xiaolan C, Yu C, Feng Q, Haifeng Y (2022) Pharmacological effects and mechanisms of tannic acid. Biomed Pharmacother 154:113561. https://doi.org/10.1016/j.biopha.2022.113561
Jung HJ, Jang HJ, Kwon TH (2021) Aquaporins implicated in the cell proliferation and the signaling pathways of cell stemness. Biochimie 188:52–60. https://doi.org/10.1016/j.biochi.2021.04.006
Kaminsky LW, Al-Sadi R, Ma TY (2021) IL-1β and the intestinal epithelial tight junction barrier. Front Immunol 12:767456. https://doi.org/10.3389/fimmu.2021.767456
Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30. https://doi.org/10.1093/nar/28.1.27
Kang SU, Shin YS, Hwang HS, Baek SJ, Lee SH, Kim CH (2012) Tolfenamic acid induces apoptosis and growth inhibition in head and neck cancer: involvement of NAG-1 expression. PLoS ONE 7(4):e34988. https://doi.org/10.1371/journal.pone.0034988
Karamanavi E, Angelopoulou K, Lavrentiadou S, Tsingotjidou A, Abas Z, Taitzoglou I, Vlemmas I, Erdman SE, Poutahidis T (2014) Urokinase-type plasminogen activator deficiency promotes neoplasmatogenesis in the colon of mice. Transl Oncol 7:174-187.e5. https://doi.org/10.1016/j.tranon.2014.02.002
Kasparová M, Siatka T, Dusek J (2003) Vliv kyseliny jasmínové na produkci anthracenových derivátů v kulture Rheum palmatum L. in vitro [Effect of jasminic acid on production of anthracene derivatives in cultures of Rheum palmatum L.]. Ceska Slov Farm 52:148–151
Khorasani SA (1970) Qarabadin-e-Kabir [great pharmacopeia. Mahmoudi Press, Tehran
Kim HJ, Jang SH, Jeong YA, Ryu PD, Kim DY, Lee SY (2010) Involvement of Kv4.1 K(+) channels in gastric cancer cell proliferation. Biol Pharm Bull 33:1754–1757. https://doi.org/10.1248/bpb.33.1754
Kim JE, Park JW, Kang MJ, Choi HJ, Bae SJ, Choi YS, Lee YJ, Lee HS, Hong JT, Hwang DY (2019) Anti-inflammatory response and muscarinic cholinergic regulation during the laxative effect of asparagus cochinchinensis in loperamide-induced constipation of SD rats. Int J Mol Sci 20:946. https://doi.org/10.3390/ijms20040946
King LS, Kozono D, Agre P (2004) From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5:687–698. https://doi.org/10.1038/nrm1469
Kisa K, Sasaki K, Yamauchi K, Kuwano S (1981) Potentiating effect of sennoside C on purgative activity of sennoside A in mice. Planta Med 42:302–303. https://doi.org/10.1055/s-2007-971647
Kizaki T, Shirato K, Sakurai T, Ogasawara JE, Oh-ishi S, Matsuoka T, Izawa T, Imaizumi K, Haga S, Ohno H (2009) Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase NF-kappaB activation. Mol Immunol 46:1195–1203. https://doi.org/10.1016/j.molimm.2008.11.005
Koh SD, Ward SM, Dick GM, Epperson A, Bonner HP, Sanders KM, Horowitz B, Kenyon JL (1999) Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle. J Physiol 515:475–487. https://doi.org/10.1111/j.1469-7793.1999.475ac.x
Koide N, Kasamatsu A, Endo-Sakamoto Y, Ishida S, Shimizu T, Kimura Y, Miyamoto I, Yoshimura S, Shiiba M, Tanzawa H, Uzawa K (2017) Evidence for critical role of lymphocyte cytosolic protein 1 in oral cancer. Sci Rep 7:43379. https://doi.org/10.1038/srep43379
Kon R, Ikarashi N, Nagoya C, Takayama T, Kusunoki Y, Ishii M, Ueda H, Ochiai W, Machida Y, Sugita K, Sugiyama K (2014) Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. J Ethnopharmacol 152:190–200. https://doi.org/10.1016/j.jep.2013.12.055
Kruse E, Uehlein N, Kaldenhoff R (2006) The aquaporins. Genome Biol 7(2):206. https://doi.org/10.1186/gb-2006-7-2-206
Kumar KK, Burgess AW, Gulbis JM (2014) Structure and function of LGR5: an enigmatic G-protein coupled receptor marking stem cells. Protein Sci 23:551–565. https://doi.org/10.1002/pro.2446
Lai S, Cheng R, Gao D, Chen YG, Deng C (2020) LGR5 constitutively activates NF-κB signaling to regulate the growth of intestinal crypts. FASEB J 34:15605–15620. https://doi.org/10.1096/fj.202001329R
Leng-Peschlow E (1993) Sennoside-induced secretion and its relevance for the laxative effect. Pharmacology 47:14–21. https://doi.org/10.1159/000139838
Li F, Wang SC, Wang X, Ren QY, Wang W, Shang GW, Zhang L, Zhang SH (2008) Novel exploration of cathartic pharmacology induced by rhubarb. Zhongguo Zhong Yao Za Zhi 33(4):481–484
Li Y, Li Y, Zong Y, Qi J, Liu K (2011) Prebiotics and oxidative stress in constipated rats. J Pediatr Gastroenterol Nutr 53(4):447–452. https://doi.org/10.1097/MPG.0b013e31821eed83
Li H, Zuo J, Tang W (2018) Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol 9:1048
Li H, Fan C, Feng C, Wu Y, Lu H, He P, Yang X, Zhu F, Qi Q, Gao Y, Zuo J, Tang W (2019a) Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity. Br J Pharmacol 176:2209–2226. https://doi.org/10.1111/bph.14667
Li H, Hei X, Li Y, Gao J, Yan Y, Zhang G, Liu Z, Zhang H (2019b) Accumulation profile of nine constituents in different years old stage and parts of Rheum palmatum L. by HPLC analysis. Nat Prod Res Dev 31:923–931
Li Q, Guo Y, Yu X, Liu W, Zhou L (2020) Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia-reperfusion injury: interactions between medicine and intestinal flora. Chin Med 15:60. https://doi.org/10.1186/s13020-020-00341-x
Li Y, Pan X, Yin M, Li C, Han L (2021) Preventive effect of lycopene in dextran sulfate sodium-induced ulcerative colitis mice through the regulation of TLR4/TRIF/NF-κB signaling pathway and tight junctions. J Agric Food Chem 69:13500–13509. https://doi.org/10.1021/acs.jafc.1c05128
Liang Z, Sham T, Yang G, Yi L, Chen H, Zhao Z (2013) Profiling of secondary metabolites in tissues from Rheum palmatum L. using laser microdissection and liquid chromatography mass spectrometry. Anal Bioanal Chem 405:4199–4212. https://doi.org/10.1007/s00216-013-6819-z
Liao S, Gan L, Lv L, Mei Z (2020) The regulatory roles of aquaporins in the digestive system. Genes Dis 8:250–258. https://doi.org/10.1016/j.gendis.2019.12.011
Lichao S, Liang P, Chunguang G, Fang L, Zhihua Y, Yuliang R (2012) Overexpression of PTGIS could predict liver metastasis and is correlated with poor prognosis in colon cancer patients. Pathol Oncol Res 18:563–569. https://doi.org/10.1007/s12253-011-9478-4
Liu Q, Li F, Li J, Yao J, Wang X, Wang C, Wang W (2009) Regulating effects of aquaporin 4 expression in LoVo cells by serum containing total anthraquinone in rheum. Zhongguo Zhong Yao Za Zhi 34:3247–3250
Liu J, Tian DA, Wang JP, Zhang SZ, Feng J, Zhao ZZ, Hao YX, Liu P (2011) Expression of aquaporin 8 and its relationship with melanosis coli. Chin Med J (engl) 124:3061–3065
Liu C, Zheng Y, Xu W, Wang H, Lin N (2014) Rhubarb tannins extract inhibits the expression of aquaporins 2 and 3 in magnesium sulphate-induced diarrhoea model. Biomed Res Int 2014:619465. https://doi.org/10.1155/2014/619465
Liu J, Kumar S, Heinzel A, Gao M, Guo J, Alvarado GF, Reindl-Schwaighofer R, Krautzberger AM, Cippà PE, McMahon J, Oberbauer R, McMahon AP (2020) Renoprotective and immunomodulatory effects of GDF15 following AKI invoked by ischemia-reperfusion injury. J Am Soc Nephrol 31:701–715. https://doi.org/10.1681/ASN.2019090876
Liu J, Wang S, Yi R, Long X, Luo G, Zhao X, He Y (2022) LimosiLactobacillus pentosus isolated from mustard relieves drug-induced constipation in mice fed a high-fat diet by modulating enteric neurotransmitter function. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-022-09991-9
Lombardi N, Bettiol A, Crescioli G, Maggini V, Gallo E, Sivelli F, Sofi F, Gensini GF, Vannacci A, Firenzuoli F (2020) Association between anthraquinone laxatives and colorectal cancer: protocol for a systematic review and meta-analysis. Syst Rev 9:19. https://doi.org/10.1186/s13643-020-1280-5
Masson N, Ellis M, Goodbourn S, Lee KA (1992) Cyclic AMP response element-binding protein and the catalytic subunit of protein kinase A are present in F9 embryonal carcinoma cells but are unable to activate the somatostatin promoter. Mol Cell Biol 12:1096–1106. https://doi.org/10.1128/mcb.12.3.1096-1106.1992
Meli R, Pirozzi C, Pelagalli A (2018) New perspectives on the potential role of aquaporins (AQPs) in the physiology of inflammation. Front Physiol 9:101. https://doi.org/10.3389/fphys.2018.00101
Mohagheghzadeh A, Dehshahri S, Hemmati S (2009) Accumulation of lignans by in vitro cultures of three Linum species. Z Naturforsch C J Biosci 64:73–76. https://doi.org/10.1515/znc-2009-1-213
Moon C, Zhang W, Sundaram N, Yarlagadda S, Reddy VS, Arora K, Helmrath MA, Naren AP (2015) Drug-induced secretory diarrhea: a role for CFTR. Pharmacol Res 102:107–112. https://doi.org/10.1016/j.phrs.2015.08.024
Moreau M, Mourah S, Dosquet C (2011) β-Catenin and NF-κB cooperate to regulate the uPA/uPAR system in cancer cells. Int J Cancer 128:1280–1292. https://doi.org/10.1002/ijc.25455
Nakajima M, Shiihara Y, Shiba Y, Sano I, Sakai T, Mizumoto A, Itoh Z (1997) Effect of 5-hydroxytryptamine on gastrointestinal motility in conscious guinea-pigs. Neurogastroenterol Motil 9:205–214. https://doi.org/10.1046/j.1365-2982.1997.d01-56.x
Namkung W, Thiagarajah JR, Phuan PW, Verkman AS (2010) Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. FASEB J 24:4178–4186. https://doi.org/10.1096/fj.10-160648
Nanda V, Miano JM (2012) Leiomodin 1, a new serum response factor-dependent target gene expressed preferentially in differentiated smooth muscle cells. J Biol Chem 287:2459–2467. https://doi.org/10.1074/jbc.M111.302224
O’Grady SM, Jiang X, Maniak PJ, Birmachu W, Scribner LR, Bulbulian B, Gullikson GW (2002) Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells. J Membr Biol 185:137–144. https://doi.org/10.1007/s00232-001-0120-3
Pan Z, Yang K, Wang H, Xiao Y, Zhang M, Yu X, Xu T, Bai T, Zhu H (2020) MFAP4 deficiency alleviates renal fibrosis through inhibition of NF-κB and TGF-β/Smad signaling pathways. FASEB J 34:14250–14263. https://doi.org/10.1096/fj.202001026R
Pandith SH, Ishfaq Khan M, Ramazan S (2021) Genus Rheum (Polygonaceae): a global perspective. CRC Press, Boca Raton
Parvinroo S, Naghibi F, Zahediasl S, Kamalinejad M, Sabetkasaei M (2014) The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats. J Ethnopharmacol 156:216–221. https://doi.org/10.1016/j.jep.2014.08.026
Pelagalli A, Squillacioti C, Mirabella N, Meli R (2016) Aquaporins in health and disease: an overview focusing on the gut of different species. Int J Mol Sci 17:1213. https://doi.org/10.3390/ijms17081213
Peplowski MA, Vegso AJ, Iablokov V, Dicay M, Zaheer RS, Renaux B, Proud D, Hollenberg MD, Beck PL, MacNaughton WK (2017) Tumor necrosis factor α decreases aquaporin 3 expression in intestinal epithelial cells through inhibition of constitutive transcription. Physiol Rep 5:e13451. https://doi.org/10.14814/phy2.13451
Prakash M, Raj B, Murthy KNC, Mohithe MP (2018) Biological functions of epicatechin: plant cell to human cell health. J Funct Foods 52:14–24
Puértolas-Balint F, Schroeder BO (2020) Does an apple a day also keep the microbes away? The interplay between diet, microbiota, and host defense peptides at the intestinal mucosal barrier. Front Immunol 11:1164. https://doi.org/10.3389/fimmu.2020.01164
Qin Y, Wang JB, Kong WJ, Zhao YL, Yang HY, Dai CM, Fang F, Zhang L, Li BC, Jin C, Xiao XH (2011) The diarrhoeogenic and antidiarrhoeal bidirectional effects of rhubarb and its potential mechanism. J Ethnopharmacol 133:1096–1102. https://doi.org/10.1016/j.jep.2010.11.041
Rauwald HW (1998) Chapter 9: herbal laxatives - influence of anthrones-anthraquinones on energy metabolism and ion transport in a model system. In: Lawson LD, Bauer R (eds) Phytomedicines of Europe. American Chemical Society, Washington
Rump K, Siffert W, Peters J, Adamzik M (2016) The transcription factor NMP4 binds to the AQP5 promoter and is a novel transcriptional regulator of the AQP5 gene. DNA Cell Biol 35:322–327. https://doi.org/10.1089/dna.2015.3110
Sadakata T, Washida M, Morita N, Furuichi T (2007) Tissue distribution of Ca2+-dependent activator protein for secretion family members CAPS1 and CAPS2 in mice. J Histochem Cytochem 55:301–311. https://doi.org/10.1369/jhc.6A7033.2006
Semrad CE (2012) Approach to the patient with diarrhea and malabsorption, Chap 142. In: Goldman L, Schafer AI (eds) Goldman's cecil medicine, 24th edn. Elsevier, Philadelphia, PA, pp 895–913. https://doi.org/10.1016/B978-1-4377-1604-7.00142-1
Seo Y, Park SY, Kim HS, Nam JS (2020) The hippo-yap signaling as guardian in the pool of intestinal stem cells. Biomedicines 8:560. https://doi.org/10.3390/biomedicines8120560
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. https://doi.org/10.1101/gr.1239303
Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C (2015) NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol 6:262. https://doi.org/10.3389/fphar.2015.00262
Sharma N, Lopez DI, Nyborg JK (2007) DNA binding and phosphorylation induce conformational alterations in the kinase-inducible domain of CREB. Implications for the mechanism of transcription function. J Biol Chem 282:19872–19883. https://doi.org/10.1074/jbc.M701435200
Shi XZ, Lindholm PF, Sarna SK (2003) NF-kappa B activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells. Gastroenterology 124:1369–1380. https://doi.org/10.1016/s0016-5085(03)00263-4
Shi LL, Xu LN, Hou SG, Lin S, Yang H, Ma TH (2006) Activation effect of cathartic natural compound rhein to CFTR chloride channel. Chem Res Chin Univ 22:312–314
Shia CS, Juang SH, Tsai SY, Chang PH, Kuo SC, Hou YC, Chao PD (2009) Metabolism and pharmacokinetics of anthraquinones in Rheum palmatum in rats and ex vivo antioxidant activity. Planta Med 75:1386–1392. https://doi.org/10.1055/s-0029-1185725
Singh R, Chaturvedi P (2021) In vitro propagation and establishment of adventitious root cultures of Rheum emodi Wall. ex Meisn for quantification of emodin production. In Vitro Cell Dev Biol-Plant 58:80–92
Song R, Cheng Y, Tian Y, Zhang ZJ (2012) A validated solidphase extraction HPLC method for the simultaneous determination of gallic acid, catechin and epicatechin in rhubarb decoction. Chin J Nat Med 10:275–278
Sun S, Wang X, Wu X, Zhao Y, Wang F, Liu X, Song Y, Wu Z, Liu M (2011) Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease. Parasites Vectors 4:186. https://doi.org/10.1186/1756-3305-4-186
Sund RB, Elvegård SO (1988) Anthraquinone laxatives: metabolism and transport of danthron and rhein in the rat small and large intestine in vitro. Pharmacology 36:144–151. https://doi.org/10.1159/000138434
Tadesse E, Engidawork E, Nedi T, Mengistu G (2017) Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice. BMC Complement Altern Med 17:190. https://doi.org/10.1186/s12906-017-1696-1
Takayama K, Tsutsumi H, Ishizu T, Okamura N (2012) The influence of rhein 8-O-β-D-glucopyranoside on the purgative action of sennoside A from rhubarb in mice. Biol Pharm Bull 35:2204–2208. https://doi.org/10.1248/bpb.b12-00632
Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20:709–726. https://doi.org/10.1016/s0896-6273(00)81010-7
Tong WD, Liu BH, Zhang LY, Xiong RP, Liu P, Zhang SB (2005) Expression of c-kit messenger ribonucleic acid and c-kit protein in sigmoid colon of patients with slow transit constipation. Int J Colorectal Dis 20:363–367. https://doi.org/10.1007/s00384-004-0679-0
Vaish V, Piplani H, Rana C, Vaiphei K, Sanyal SN (2013) NSAIDs may regulate EGR-1-mediated induction of reactive oxygen species and non-steroidal anti-inflammatory drug-induced gene (NAG)-1 to initiate intrinsic pathway of apoptosis for the chemoprevention of colorectal cancer. Mol Cell Biochem 378:47–64. https://doi.org/10.1007/s11010-013-1593-y
Valcheva-Kuzmanova S, Kuzmanov K (2011) Inhibitory effect of Aronia melanocarpa fruit juice on intestinal transit rate in rats. Acta Aliment 40:396–399
van Gorkom BA, de Vries EG, Karrenbeld A, Kleibeuker JH (1999) Review article: anthranoid laxatives and their potential carcinogenic effects. Aliment Pharmacol Ther 13:443–452. https://doi.org/10.1046/j.1365-2036.1999.00468.x
van Gorkom BA, Karrenbeld A, van der Sluis T, Zwart N, de Vries EG, Kleibeuker JH (2001) Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use? J Pathol 194:493–499. https://doi.org/10.1002/path.914
van Hoestenberghe A, De Witte P, Geboes K, Eyssen H, Nijs G, Lemli J (1992) The effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free rats. Eur J Pharmacol 212:121–123. https://doi.org/10.1016/0014-2999(92)90084-h
Viennois E, Chen F, Merlin D (2013) NF-κB pathway in colitis-associated cancers. Transl Gastrointest Cancer 2:21–29. https://doi.org/10.3978/j.issn.2224-4778.2012.11.01
Vladimirovna FT, Faridovich KК, Igorevich RV, Mikhailovich RL, Georgievich TD, Victorovich ED, Olegovich KD, Nikolaevna PA, Mikhailovna LM (2020) Genetic factors of polygenic urolithiasis. Urologia 87:57–64. https://doi.org/10.1177/0391560319898375
Wang JB, Qin Y, Kong WJ, Wang ZW, Zeng LN, Fang F, Jin C, Zhao YL, Xiao XH (2011) Identification of the antidiarrhoeal components in official rhubarb using liquid chromatography-tandem mass spectrometry. Food Chem 129:1737–1743
Wang H, Song H, Yue J, Li J, Hou YB, Deng JL (2012) Rheum officinale (a traditional Chinese medicine) for chronic kidney disease. Cochrane Database Syst Rev 7:CD008000. https://doi.org/10.1002/14651858.CD008000.pub2
Wang XM, Hou XQ, Zhang YQ, Li Y (2014) Morphological variation in leaf dissection of Rheum palmatum complex (Polygonaceae). PLoS ONE 9:e110760. https://doi.org/10.1371/journal.pone.0110760
Wang Q, Lu ZW, Liu YH, Wang ML, Fu S, Zhang QQ, Zhao HZ, Zhang ZX, Xie ZY, Huang ZH, Yu HH, Zhou WJ, Gao XY (2017) Rapid analysis on phenolic compounds in Rheum palmatum based on UPLC-Q-TOF/MSE combined with diagnostic ions filter. Zhongguo Zhong Yao Za Zhi 42:1922–1931. https://doi.org/10.19540/j.cnki.cjcmm.20170317.001
Wang H, Xu J, Lazarovici P, Quirion R, Zheng W (2018) cAMP response element-binding protein (CREB): a possible signaling molecule link in the pathophysiology of Schizophrenia. Front Mol Neurosci 11:255. https://doi.org/10.3389/fnmol.2018.00255
Wang Z, Cheng Y, Su W, Zhang H, Li C, Routledge MN, Gong Y, Qiao B (2021) Organ specific differences in alteration of aquaporin expression in rats treated with sennoside a, senna anthraquinones and rhubarb anthraquinones. Int J Mol Sci 22:8026. https://doi.org/10.3390/ijms22158026
Woolf EC, Curley KL, Liu Q, Turner GH, Charlton JA, Preul MC, Scheck AC (2015) The ketogenic diet alters the hypoxic response and affects expression of proteins associated with angiogenesis, invasive potential and vascular permeability in a mouse glioma model. PLoS ONE 10:e0130357. https://doi.org/10.1371/journal.pone.0130357
Wu W, Yan R, Yao M, Zhan Y, Wang Y (2014) Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract. Biomed Chromatogr 28:564–572. https://doi.org/10.1002/bmc.3070
Wu WJ, Yan R, Li T, Li YP, Zhou RN, Wang YT (2017) Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat. J Ethnopharmacol 198:600–607. https://doi.org/10.1016/j.jep.2017.01.049
Xie C, Jiang XH, Zhang JT, Sun TT, Dong JD, Sanders AJ, Diao RY, Wang Y, Fok KL, Tsang LL, Yu MK, Zhang XH, Chung YW, Ye L, Zhao MY, Guo JH, Xiao ZJ, Lan HY, Ng CF, Lau KM, Chan HC et al (2013) CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer. Oncogene 32:2282-2291.e22917. https://doi.org/10.1038/onc.2012.251
Xie L, Wang Y, Luo G, Wenjuan Zh, Miao J, Tang S, Jiang Q, Guan Y, Gao X (2020) Identification of the multiple bioactive derivatives and their endogenous molecular targets that may mediate the laxative effect of rhubarb in rats. J Trad Chin Med Sci 7:210–220
Xiong Y, Chen L, Fan L, Wang L, Zhou Y, Qin D, Sun Q, Wu J, Cao S (2018) Free total rhubarb anthraquinones protect intestinal injury via regulation of the intestinal immune response in a rat model of severe acute pancreatitis. Front Pharmacol 9:75. https://doi.org/10.3389/fphar.2018.00075
Xu L, Ting-Lou LN, Zhu X, Chen Y, Yang J (2009) Emodin augments calcium activated chloride channel in colonic smooth muscle cells by Gi/Go protein. Eur J Pharmacol 615:171–176. https://doi.org/10.1016/j.ejphar.2009.04.045
Yagi T, Miyawaki Y, Nishikawa A, Yamauchi K, Kuwano S (1991) Suppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in rats. J Pharm Pharmacol 43:307–310. https://doi.org/10.1111/j.2042-7158.1991.tb06695.x
Yan B, Wang D, Dong S, Cheng Z, Na L, Sang M, Yang H, Yang Z, Zhang S, Yan Z (2017) Palmatine inhibits TRIF-dependent NF-κB pathway against inflammation induced by LPS in goat endometrial epithelial cells. Int Immunopharmacol 45:194–200. https://doi.org/10.1016/j.intimp.2017.02.004
Yao WY, Zhou YF, Qian AH, Zhang YP, Qiao MM, Zhai ZK, Yuan YZ, Yang SL (2015) Emodin has a protective effect in cases of severe acute pancreatitis via inhibition of nuclear factor κB activation resulting in antioxidation. Mol Med Rep 11:1416–1420. https://doi.org/10.3892/mmr.2014.2789
Yavari M (2022) Hot and cold theory: the path towards personalized medicine. Springer International Publishing, New York
Yin Y, Gao D, Wang Y, Wang ZH, Wang X, Ye J, Wu D, Fang L, Pi G, Yang Y, Wang XC, Lu C, Ye K, Wang JZ (2016) Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling. Proc Natl Acad Sci U S A 113:E3773–E3781. https://doi.org/10.1073/pnas.1604519113
Yu H, Liu L, Wang K, Wu H, Wang W, Zhang X, Cui G, Cui X, Huang J (2018) Upregulation of aquaporin 3 expression by diterpenoids in Euphorbia pekinensis is associated with activation of the NF-κB signaling pathway in the co-culture system of HT-29 and RAW 264.7 cells. Biochimie 144:153–159. https://doi.org/10.1016/j.biochi.2017.11.006
Zalucki YM, Power PM, Jennings MP (2007) Selection for efficient translation initiation biases codon usage at second amino acid position in secretory proteins. Nucleic Acids Res 35:5748–5754. https://doi.org/10.1093/nar/gkm577
Zeng LN, Ma ZJ, Zhao YL, Zhang LD, Li RS, Wang JB, Zhang P, Yan D, Li Q, Jiang BQ, Pu SB, Lü Y, Xiao XH (2013) The protective and toxic effects of rhubarb tannins and anthraquinones in treating hexavalent chromium-injured rats: the Yin/Yang actions of rhubarb. J Hazard Mater 246–247:1–9. https://doi.org/10.1016/j.jhazmat.2012.12.004
Zewdie KA, Bhoumik D, Wondafrash DZ, Tuem KB (2020) Evaluation of in-vivo antidiarrhoeal and in-vitro antibacterial activities of the root extract of Brucea antidysenterica J. F. Mill (Simaroubaceae). BMC Complement Med Ther 20:201. https://doi.org/10.1186/s12906-020-03001-7
Zhang WS, Li F, Bao JQ (2008) Regulatory effect of anthraquinone derivatives from rhubarb on aquaporin 4 expression in colon of rats and in LoVo cell line. Zhongguo Zhong Xi Yi Jie He Za Zhi 28:818–823
Zhang RZ, Qiu H, Wang N, Long FL, Mao DW (2015) Effect of Rheum palmatum L. on NF-κB signaling pathway of mice with acute liver failure. Pac J Trop Med 8:841–847. https://doi.org/10.1016/j.apjtm.2015.09.011
Zhang C, Jiang J, Tian F, Zhao J, Zhang H, Zhai Q, Chen W (2020) Meta-analysis of randomized controlled trials of the effects of probiotics on functional constipation in adults. Clin Nutr ESPEN 39:2960–2969. https://doi.org/10.1016/j.clnu.2020.01.005
Zhao J, Ren J, Liu S, Gong Y, Meng P, Tan H, Chen Y (2021a) Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA-CREB-BDNF signaling pathway. Exp Ther Med 22:1442. https://doi.org/10.3892/etm.2021.10877
Zhao Q, Chen YY, Xu DQ, Yue SJ, Fu RJ, Yang J, Xing LM, Tang YP (2021b) Action mode of gut motility, fluid and electrolyte transport in chronic constipation. Front Pharmacol 12:630249. https://doi.org/10.3389/fphar.2021.630249
Zheng YF, Liu CF, Lai WF, Xiang Q, Li ZF, Wang H, Lin N (2014) The laxative effect of emodin is attributable to increased aquaporin 3 expression in the colon of mice and HT-29 cells. Fitoterapia 96:25–32. https://doi.org/10.1016/j.fitote.2014.04.002
Zhou X, Geng L, Wang D, Yi H, Talmon G, Wang J (2017) R-Spondin1/LGR5 activates TGFβ signaling and suppresses colon cancer metastasis. Cancer Res 77:6589–6602. https://doi.org/10.1158/0008-5472.CAN-17-0219
Zhu J, Chen L, Shi J, Liu S, Liu Y, Zheng D (2014) TRAIL receptor deficiency sensitizes mice to dextran sodium sulphate-induced colitis and colitis-associated carcinogenesis. Immunology 141:211–221. https://doi.org/10.1111/imm.12181
Zhu X, Yang M, Lin Z, Mael SK, Li Y, Zhang L, Kong Y, Zhang Y, Ren Y, Li J, Wang Z, Zhang Y, Yang B, Huang T, Guan F, Li Z, Moses RE, Li L, Wang B, Li X, Zhang B et al (2022) REGγ drives Lgr5+ stem cells to potentiate radiation induced intestinal regeneration. Sci China Life Sci 65:1608–1623. https://doi.org/10.1007/s11427-021-2018-7
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Mosleh, G., Zaeri, M., Hemmati, S. et al. A comprehensive review on rhubarb astringent/ laxative actions and the role of aquaporins as hub genes. Phytochem Rev 22, 565–586 (2023). https://doi.org/10.1007/s11101-022-09851-y
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DOI: https://doi.org/10.1007/s11101-022-09851-y