Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon

Kim,Ji  Eun; Koh,Eun  Kyoung; Song,Sung  Hwa; Sung,Ji  Eun; Lee,Hyun  Ah; Lee,Hong  Gu; Choi,Young  Whan; Hwang,Dae  Youn

doi:10.3892/mmr.2016.5983

Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon

Authors:
- Ji Eun Kim
- Eun Kyoung Koh
- Sung Hwa Song
- Ji Eun Sung
- Hyun Ah Lee
- Hong Gu Lee
- Young Whan Choi
- Dae Youn Hwang
View Affiliations

Affiliations: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam‑do 627‑706, Republic of Korea, Department of Animal Science and Technology, College of Animal Bioscience and Technology, Konkuk University, Seoul 143‑701, Republic of Korea, Department of Horticultural Bioscience, College of Natural Resources and Life Science, Pusan National University, Miryang, Gyeongsangnam‑do 627‑706, Republic of Korea
Published online on: December 5, 2016 https://doi.org/10.3892/mmr.2016.5983
Pages: 431-441

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)‑induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5‑HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)‑18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidate‑treated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5‑HMF and AD treatment groups. In IEC‑18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5‑HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5‑HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC‑18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5‑HT receptor signaling pathway.

View Figures

View References

1	Young SN: How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 32:394–399. 2007.PubMed/NCBI
2	Ahn J and Ehrenpreis ED: Emerging treatments for irritable bowel syndrome. Expert Opin pharmacother. 3:9–21. 2002. View Article : Google Scholar : PubMed/NCBI
3	Bulbring E and Crema A: The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa. J Physiol. 146:18–28. 1959. View Article : Google Scholar : PubMed/NCBI
4	Gershon MD: Serotonin: Its role and receptors in enteric neurotransmission. Adv Exp Med Biol. 294:221–230. 1991. View Article : Google Scholar : PubMed/NCBI
5	Baker DE: Rationale for using serotonergic agents to treat irritable bowel syndrome. Am J Health Syst Pharm. 62:700–711; quiz 712–713. 2005.PubMed/NCBI
6	Sikander A, Rana SV and Prasad KK: Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta. 403:47–55. 2009. View Article : Google Scholar : PubMed/NCBI
7	Costedio MM, Hyman N and Mawe GM: Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum. 50:376–388. 2007. View Article : Google Scholar : PubMed/NCBI
8	Crowell MD: Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 141:1285–1293. 2004. View Article : Google Scholar : PubMed/NCBI
9	El-Salhy M, Danielsson A, Stenling R and Grimelius L: Colonic endocrine cells in inflammatory bowel disease. J Intern Med. 242:413–419. 1997. View Article : Google Scholar : PubMed/NCBI
10	Lincoln J, Crowe R, Kamm MA, Burnstock G and Lennard-Jones JE: Serotonin and 5-hydroxyindol acetic acid are increased in the sigmoid colon in severe idiopathic constipation. Gastroenterol. 98:1219–1225. 1990. View Article : Google Scholar
11	Zhao R, Baig MK, Wexner SD, Chen W, Singh JJ, Nogueras JJ and Woodhouse S: Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia. Dis Colon Rectum. 43:858–863. 2000. View Article : Google Scholar : PubMed/NCBI
12	Callahan MJ: Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. J Clin Gastroenterol. 35:(1 Suppl). S58–S67. 2002. View Article : Google Scholar : PubMed/NCBI
13	Kamm MA, Müller-Lissner S, Talley NJ, Tack J, Boeckxstaens G, Minushkin ON, Kalinin A, Dzieniszewski J, Haeck P, Fordham F, et al: Tegaserod for the treatment of chronic constipation: A randomized, double-blind, placebo-controlled multinational study. Am J Gastroenterol. 100:362–372. 2005. View Article : Google Scholar : PubMed/NCBI
14	von der Ohe MR, Hanson RB and Camilleri M: Serotonergic mediation of postprandial colonic tonic and phasic responses in humans. Gut. 35:536–541. 1994. View Article : Google Scholar : PubMed/NCBI
15	Kakino M, Izuta H, Ito T, Tsuruma K, Araki Y, Shimazawa M, Oyama M, Iinuma M and Hara H: Agarwood induced laxative effects via acetylcholine receptors on loperamide-induced constipation in mice. Biosci Biotechnol Biochem. 74:1550–1555. 2010. View Article : Google Scholar : PubMed/NCBI
16	Lee HY, Kim JH, Jeung HW, Lee CU, Kim DS, Li B, Lee GH, Sung MS, Ha KC, Back HI, et al: Effects of Ficus carica paste on loperamide-induced constipation in rats. Food Chem Toxicol. 50:895–902. 2012. View Article : Google Scholar : PubMed/NCBI
17	Méité S, Bahi C, Yéo D, Datté JY, Djaman JA and N'guessan DJ: Laxative activities of Mareya micrantha (Benth.) Müll. Arg. (Euphorbiaceae) leaf aqueous extract in rats. BMC Complement Altern Med. 10:72010. View Article : Google Scholar : PubMed/NCBI
18	Wintola OA, Sunmonu TO and Afolayan AJ: The effect of Aloe ferox Mill. in the treatmentet of loperamide-induced constipation in Wistar rats. BMC Gastroenterol. 10:952010. View Article : Google Scholar : PubMed/NCBI
19	Kim JE, Lee YJ, Kwak MH, Ko J, Hong JT and Hwang DY: Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats. BMC Complement Altern Med. 13:3332013. View Article : Google Scholar : PubMed/NCBI
20	Kim BJ: Shengmaisan refulates pacemaker potentials in interstitial cells of cajal in mice. J Pharmacopuncture. 16:36–42. 2013. View Article : Google Scholar : PubMed/NCBI
21	Thyberg J, Hedin U, Sjölund M, Palmberg L and Bottger BA: Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis. 10:966–990. 1990. View Article : Google Scholar : PubMed/NCBI
22	Parajuli SP, Choi S, Lee J, Kim YD, Park CG, Kim MY, Kim HI, Yeum CH and Jun JY: The inhibitory effects of hydrogen sulfide on pacemaker activity of interstitial cells of cajal from mouse small intestine. Korean J Physiol Pharmacol. 14:83–89. 2010. View Article : Google Scholar : PubMed/NCBI
23	Pari L, Monisha P and Jalaludeen A Mohamed: Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur J Pharmacol. 691:143–150. 2012. View Article : Google Scholar : PubMed/NCBI
24	Huang CH, Ku CY and Jan TR: Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy. Planta Med. 75:1300–1305. 2009. View Article : Google Scholar : PubMed/NCBI
25	Yamada T, Hoshino M, Hayakawa T, Ohhara H, Yamada H, Nakazawa T, Inagaki T, Iida M, Ogasawara T, Uchida A, et al: Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats. Am J Physiol. 273:G355–G364. 1997.PubMed/NCBI
26	Black CT, Hennessey PJ, Ford EG and Andrassy RJ: Protein glyosylation and collagen metabolism in normal and diabetic rats. J Surg Res. 47:200–202. 1989. View Article : Google Scholar : PubMed/NCBI
27	Nicolau CT, Teitel P, Bratu V, Xenakis A and Butoianu E: Favorable therapeutic effect of adenosine monophosphate (AMP) in a case of compensated chronic hemolytic disease due to insufficiency of erythrocytic energetic metabolism. Med Interna (Bucur). 17:423–430. 1965.(In Romanian). PubMed/NCBI
28	Tsukamoto H: Extracellular adenosine is a therapeutic target for limiting graft-versus-host disease and enhancing the graft-versus-tumor effect against hematopoietic malignancy. Yakugaku Zasshi. 134:1021–1027. 2014.(In Japanese). View Article : Google Scholar : PubMed/NCBI
29	Krishnaiah YS, Kumar MS, Raju V, Lakshmi M and Rama B: Penetration-enhancing effect of ethanolic solution of menthol on transdermal permeation of ondansetron hydrochloride across rat epidermis. Drug Deliv. 15:227–234. 2008. View Article : Google Scholar : PubMed/NCBI
30	Oswald S, Giessmann T, Luetjohann D, Wegner D, Rosskopf D, Weitschies W and Siegmund W: Disposition and sterol-lowering effect of ezetimibe are influenced by single-dose coadministration of rifampin, an inhibitor of multidrug transport proteins. Clin Pharmacol Ther. 80:477–485. 2006. View Article : Google Scholar : PubMed/NCBI
31	Herz MJ, Kahan E, Zalevski S, Aframian R, Kuznitz D and Reichman S: Constipation: A different entity for patients and doctors. Fam Pract. 13:156–159. 1996. View Article : Google Scholar : PubMed/NCBI
32	Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ and Müller-Lissner SA: Functional bowel disorders and functional abdominal pain. Gut. 45:(Suppl 2). II43–II47. 1999.PubMed/NCBI
33	Raju J and Rao CV: Diosgenin, a steroid saponin constituent of Yams and Fenugreek: Emerging evidence for applications in medicineBioactive Compounds in Phytomedicine. Rasooli I: InTech; Rijeka: pp. 125–142. 2012
34	Taylor WG, Elder JL, Chang PR and Richards KW: Microdetermination of diosgenin from fenugreek (Trigonella foenum-graecum) seeds. J Agric Food Chem. 48:5206–5210. 2000. View Article : Google Scholar : PubMed/NCBI
35	Sato K, Fujita S and Iemitsu M: Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats. J Steroid Biochem Mol Biol. 143:152–159. 2014. View Article : Google Scholar : PubMed/NCBI
36	Barke AJ and Julius D: Signaling by extracellular nucleotides. Annu Rev Cell Dev Biol. 12:519–541. 1996. View Article : Google Scholar : PubMed/NCBI
37	Knowler MR, Clarke LL and Boucher RC: Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med. 325:533–538. 1991. View Article : Google Scholar : PubMed/NCBI
38	Lethem MI, Dowell ML, Van Scott M, Yankaskas JR, Egan T, Boucher RC and Davis CW: Nucleotide regulation of goblet cells in human airway epithelial explants: Normal exocytosis in cystic fibrosis. Am J Respir Cell Mol Biol. 9:315–322. 1993. View Article : Google Scholar : PubMed/NCBI
39	Ralevic V and Burnstock G: Receptors for purines and pyrimidines. Pharmacol Rev. 50:413–492. 1998.PubMed/NCBI
40	Falkengurger BH, Dickson EJ and Hille B: Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling. J Gen Physiol. 141:537–555. 2013. View Article : Google Scholar : PubMed/NCBI
41	Shimotoyodome A, Meguro S, Hase T, Tokimitsu I and Sakata T: Sulfated polysaccharides, but not cellulose, increase colonic mucus in rats with loperamide-induce constipation. Dig Dis Sci. 46:1482–1489. 2001. View Article : Google Scholar : PubMed/NCBI
42	Snape WJ Jr: The effect of methylcellulose on symptoms of constipation. Clin Ther. 11:572–579. 1989.PubMed/NCBI