Generic placeholder image

Current Bioactive Compounds

Author(s): Lalitha Vivekanandan*, Prabha Thangavelu, Jagadeeswaran Murugesan and Hemalatha Selvaraj

DOI: 10.2174/1573407219666230815121205

DownloadDownload PDF Flyer Cite As
Role of Sapindus emarginatus Pericarp Extract in Gut Serotonin Level and its Emetic Activity in Animal Models

Article ID: e150823219711 Pages: 8

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Emesis is a complex and distressing protective mechanism that helps to remove toxic substances from the stomach and prevent further ingestion. The emetics and cathartics are predominantly used for accidental and intentional ingestion of poisons or toxins. The availability and usage of emetics in humans are limited because of their side effects. Therefore, to treat poisoned people, we need effective medications. Sapindus emarginatus Vahl., often called soapnut, is a member of the Sapindaceae family. They have historically been used as emetic, antipruritic, laxative, antifertility, and anti-inflammatory medicines.

Objective: This study aims to assess the gut serotonin level and emetic effect of Sapindus emarginatus hydroethanolic pericarp extract (HESE) by using animal models.

Methods: Gravimetric analysis was used to determine the HESE's saponin content. The emetic effect of the HESE at a dose of 250, 500, 1000, and 2000 mg/kg was evaluated by copper sulfateinduced emesis in the chick model and cisplatin-induced emesis in the rat-pica model. The serotonin level in rat intestinal mucosa was measured by spectrofluorimetry.

Results: HESE was estimated to contain 11.92% saponin. The extract at high doses of 1000 and 2000 mg/kg showed emetic activity evidenced by increased frequency of retching in chick, increased kaolin intake, and anorexia in the rat-pica model. The extract showed a significant increase in serotonin levels in the proximal part of the small intestine in comparison with normal animals.

Conclusion: According to the results of the current investigation, which employed various animal models, the HESE demonstrated appreciable emetic activity. The extract at a high dose showed a significant emetic effect due to increased serotonin levels in the gut. The HESE was discovered to be a strong contender for the treatment of poisoned patients. More research are required to validate their adverse effects of frequent usage.

Keywords: Sapindus emarginatus, serotonin, saponin, cisplatin, pica, copper sulfate.

Graphical Abstract

[1]
Joseph, F. Intestinal and colonic chemoreception and motility, Quantitative human physiology, 2nd ed.; Academic press: Massachusetts, 2017, pp. 796-809.
[2]
Albertson, T.E.; Owen, K.P.; Sutter, M.E.; Chan, A.L. Gastrointestinal decontamination in the acutely poisoned patient. Int. J. Emerg. Med., 2011, 4(1), 65.
[http://dx.doi.org/10.1186/1865-1380-4-65] [PMID: 21992527]
[3]
Medhi, P.K.; Gohain, K. Study on the antiemetic property of methanolic stem extract of Swertia chirata using chick emesis model. Int. J. Basic Clin. Pharmacol., 2019, 8(2), 327.
[http://dx.doi.org/10.18203/2319-2003.ijbcp20190155]
[4]
Andrews, P.L.R.; Horn, C.C. Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases. Auton. Neurosci., 2006, 125(1-2), 100-115.
[http://dx.doi.org/10.1016/j.autneu.2006.01.008] [PMID: 16556512]
[5]
Andrews, P.L.R.; Sanger, G.J. Nausea and the quest for the perfect anti-emetic. Eur. J. Pharmacol., 2014, 722(722), 108-121.
[http://dx.doi.org/10.1016/j.ejphar.2013.09.072] [PMID: 24157981]
[6]
Ahmed, S.; Hasan, M.M.; Ahmed, S.W.; Mahmood, Z.A.; Azhar, I.; Habtemariam, S. Antiemetic effects of bioactive natural products. Phytopharmacology, 2013, 4(2), 390-433.
[7]
Koch, K.L.; Hasler, W.L. Nausea and vomiting: Diagnosis and treatment; Springer: New York, 2016.
[8]
Sanger, G.J.; Andrews, P.L.R. A history of drug discovery for treatment of nausea and vomiting and the implications for future research. Front. Pharmacol., 2018, 9, 913.
[http://dx.doi.org/10.3389/fphar.2018.00913] [PMID: 30233361]
[9]
Scorza, K.; Williams, A.; Phillips, J.D.; Shaw, J. Evaluation of nausea and vomiting. Am. Fam. Physician, 2007, 76(1), 76-84.
[PMID: 17668843]
[10]
De Ponti, F. Pharmacology of serotonin: What a clinician should know. Gut, 2004, 53(10), 1520-1535.
[http://dx.doi.org/10.1136/gut.2003.035568] [PMID: 15361507]
[11]
Decker, W.J. In quest of emesis: Fact, fable, and fancy. Clin. Toxicol., 1971, 4(3), 383-387.
[http://dx.doi.org/10.3109/15563657108990490] [PMID: 4151103]
[12]
Moder, K.G.; Hurley, D.L. Fatal hypernatremia from exogenous salt intake: Report of a case and review of the literature. Mayo Clin. Proc., 1990, 65(12), 1587-1594.
[http://dx.doi.org/10.1016/S0025-6196(12)62194-6] [PMID: 2255221]
[13]
Holtzman, N.A.; Haslam, R.H.A. Elevation of serum copper following copper sulfate as an emetic. Pediatrics, 1968, 42(1), 189-193.
[http://dx.doi.org/10.1542/peds.42.1.189] [PMID: 4385403]
[14]
Olson, K.R.; Anderson, I.B.; Benowitz, N.L.; Blanc, P.D.; Clark, R.F.; Kearney, T.E.; Kim-Katz, S.Y.; Wu, A.H. Poisoning & drug over-dose.Lange Medical Books; McGraw-Hill, 2007.
[15]
Hasegawa, M.; Sasaki, T.; Sadakane, K.; Tabuchi, M.; Takeda, Y.; Kimura, M.; Fujii, Y. Studies for the emetic mechanisms of ipecac syr-up (TJN-119) and its active components in ferrets: Involvement of 5-hydroxytryptamine receptors. Jpn. J. Pharmacol., 2002, 89(2), 113-119.
[http://dx.doi.org/10.1254/jjp.89.113] [PMID: 12120752]
[16]
Manoguerra, A.S.; Cobaugh, D.J. Guideline on the use of ipecac syrup in the out-of-hospital management of ingested poisons. Clin. Toxicol., 2005, 43(1), 1-10.
[http://dx.doi.org/10.1081/CLT-46735]
[17]
Position paper: Cathartics. J. Toxicol. Clin. Toxicol., 2004, 42(3), 243-253.
[http://dx.doi.org/10.1081/CLT-120039801] [PMID: 15362590]
[18]
Sahu, N.; Achari, B. Advances in structural determination of saponins and terpenoid glycosides. Curr. Org. Chem., 2001, 5(3), 315-334.
[http://dx.doi.org/10.2174/1385272013375607]
[19]
Grover, R.K.; Roy, A.D.; Roy, R.; Joshi, S.K.; Srivastava, V.; Arora, S.K. Complete1H and13C NMR assignments of six saponins fromSapindus trifoliatus. Magn. Reson. Chem., 2005, 43(12), 1072-1076.
[http://dx.doi.org/10.1002/mrc.1675] [PMID: 16142834]
[20]
Deshmukh, A.; Bansal, L. Sapindus emarginatus Vahl as a natural scouring agent in the dyeing of cotton with Carissa carandas leaf extract. Biolife, 2014, 2(2), 599-604.
[21]
Dhar, J.D.; Bajpai, V.K.; Setty, B.S.; Kamboj, V.P. Morphological changes in human spermatozoa as examined under scanning electron microscope after in vitro exposure to saponins isolated from Sapindus mukorossi. Contraception, 1989, 39(5), 563-568.
[http://dx.doi.org/10.1016/0010-7824(89)90111-X] [PMID: 2721200]
[22]
Vivekanandan, L.; Bharathi, G.S.S.; Murugesan, J.; Natarajan, K.; Thangavel, S. Anti-alzheimer’s and antioxidant activity of ethanolic seed extract of sapindus emarginatus vahl on scopolamine-induced cognitive impairment in mice. Adv. Pharmacol. Pharma., 2022, 10(3), 190-198.
[http://dx.doi.org/10.13189/app.2022.100305]
[23]
Mejo, C.K.; Junaid, R.P.; Sheik, H.; Vivekanandan, L.; Singaravel, S.; Thangavel, S. Evaluation of antianxiety activity of ethanolic extract of Sapindus emerginatus flowers in experimental animal models. Int. J. Pharm. Chem. Biol. Sci., 2015, 5(4), 790-795.
[24]
Vivekanandan, L.; Mandere, R.G.; Thangavel, S. Evaluation of the laxative activity of saponin enriched hydroethanolic pericarp extract of sapindus emarginatus in animal models. Curr. Bioact. Compd., 2021, 17(6), e010621186264.
[http://dx.doi.org/10.2174/1573407216999200924162315]
[25]
Lalitha, V.; Rajalakshmi, M.; Kiruthiga, N.; Hajasherief, S.; Sengottuvelu, S.; Sivakumar, T. Anti-alzheimer’s activity of methanolic tender green pod extract of cyamopsis tetragonoloba (l.) taub. on scopolamine induced amnesia in mice. Curr. Bioact. Compd., 2022, 18(7), 39-49.
[26]
Korah, M.; Rahman, J.; Rajeswari, R.; Sherief, H.; Lalitha, V.; Sengottavelu, S.; Sivakumar, T. Evaluation of diuretic efficacy and antiuro-lithiatic potential of ethanolic leaf extract of Annona squamosa Linn. in experimental animal models. Indian J. Pharmacol., 2020, 52(3), 196-202.
[http://dx.doi.org/10.4103/ijp.IJP_92_18] [PMID: 32874002]
[27]
Hudson, B.J.F.; Ei -Difrawi, E.A. The sapogenins of the seeds of four lupin species. J. Plant Foods, 1979, 3(3), 181-186.
[http://dx.doi.org/10.1080/0142968X.1979.11904227]
[28]
Ahmed, S.; Onocha, A.P. Antiemetic activity of tithonia diversifolia (HemsL) A Gray leaves in copper sulphate induced chick emesis model. Am. J. Phytomed. Clin. Therapeut., 2013, 1, 734-739.
[29]
Aleem, A.; Janbaz, K.H. Dual mechanisms of anti-muscarinic and Ca ++ antagonistic activities to validate the folkloric uses of Cyperus niveus Retz. as antispasmodic and antidiarrheal. J. Ethnopharmacol., 2018, 213, 138-148.
[http://dx.doi.org/10.1016/j.jep.2017.11.006] [PMID: 29122673]
[30]
Raghavendran, H.R.B.; Rekha, S.; Shin, J.W.; Kim, H.G.; Wang, J.H.; Park, H.J.; Choi, M.K.; Cho, J.H.; Son, C.G. Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model. Food Chem. Toxicol., 2011, 49(1), 215-221.
[http://dx.doi.org/10.1016/j.fct.2010.10.019] [PMID: 20969914]
[31]
Tian, L.; Qian, W.; Qian, Q.; Zhang, W.; Cai, X. Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems. J. Nat. Med., 2020, 74(2), 353-370.
[http://dx.doi.org/10.1007/s11418-019-01372-x] [PMID: 31768887]
[32]
Lalitha, V.; Jagadeeswaran, M.; Kalpana, K.G.; Ramamoothi, M.; Sivakumar, T. Alteration in gut serotonin level induced by ethanolic ripen fruit extract of ficus carica and its mechanism against constipation in animal models. Nat. Volatiles Essent. Oils, 2021, 8(5), 5604-5620.
[33]
Schlumpf, M.; Lichtensteiger, W.; Langemann, H.; Waser, P.G.; Hefti, F. A fluorometric micromethod for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochem. Pharmacol., 1974, 23(17), 2437-2446.
[http://dx.doi.org/10.1016/0006-2952(74)90235-4] [PMID: 4429570]
[34]
Horn, C. The medical implications of gastrointestinal vagal afferent pathways in nausea and vomiting. Curr. Pharm. Des., 2014, 20(16), 2703-2712.
[http://dx.doi.org/10.2174/13816128113199990568] [PMID: 23886386]
[35]
Zhong, W.; Shahbaz, O.; Teskey, G.; Beever, A.; Kachour, N.; Venketaraman, V.; Darmani, N.A. Mechanisms of nausea and vomiting: Current knowledge and recent advances in intracellular emetic signaling systems. Int. J. Mol. Sci., 2021, 22(11), 5797.
[http://dx.doi.org/10.3390/ijms22115797] [PMID: 34071460]
[36]
Yates, B.J.; Catanzaro, M.F.; Miller, D.J.; McCall, A.A. Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: Potential contributions to motion sickness. Exp. Brain Res., 2014, 232(8), 2455-2469.
[http://dx.doi.org/10.1007/s00221-014-3937-6] [PMID: 24736862]
[37]
Horn, C.C.; Meyers, K.; Lim, A.; Dye, M.; Pak, D.; Rinaman, L.; Yates, B.J. Delineation of vagal emetic pathways: Intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014, 306(5), R341-R351.
[http://dx.doi.org/10.1152/ajpregu.00413.2013] [PMID: 24430885]
[38]
Murphey, C.P.; Shulgach, J.A.; Amin, P.R.; Douglas, N.K.; Bielanin, J.P.; Sampson, J.P.; Horn, C.C.; Yates, B.J. Physiological changes associated with copper sulfate-induced emesis in felines. bioRxiv, 2022, 2022, 10.
[http://dx.doi.org/10.1101/2022.10.20.512908]
[39]
Cubeddu, L.X.; O’Connor, D.T.; Parmer, R.J. Plasma chromogranin: A marker of serotonin release and of emesis associated with cispla-tin chemotherapy. J. Clin. Oncol., 1995, 13(3), 681-687.
[http://dx.doi.org/10.1200/JCO.1995.13.3.681] [PMID: 7533826]
[40]
Lindley, C.; Blower, P. Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis. Am. J. Health Syst. Pharm., 2000, 57(18), 1685-1697.
[http://dx.doi.org/10.1093/ajhp/57.18.1685] [PMID: 11006796]
[41]
Aung, H.H.; Dey, L.; Mehendale, S.; Xie, J.T.; Wu, J.A.; Yuan, C.S. Scutellaria baicalensis extract decreases cisplatin-induced pica in rats. Cancer Chemother. Pharmacol., 2003, 52(6), 453-458.
[http://dx.doi.org/10.1007/s00280-003-0694-9] [PMID: 12942313]
[42]
Chen, D.; Guo, Y.; Yang, Y. Liujunanwei decoction attenuates cisplatin-induced nausea and vomiting in a Rat-Pica model partially mediat-ed by modulating the gut microbiome. Front. Cell. Infect. Microbiol., 2022, 12, 876781.
[43]
Schwörer, H.; Racké, K.; Kilbinger, H. Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guinea-pig: Involvement of 5-HT3 receptors. Naunyn Schmiedebergs Arch. Pharmacol., 1991, 344(2), 143-149.
[http://dx.doi.org/10.1007/BF00167211] [PMID: 1719432]
[44]
Sathyanath, R.; Hanumantha Rao, B.R.; Kim, H.G.; Cho, J.H.; Son, C.G. Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats. Pharm. Biol., 2013, 51(8), 1052-1060.
[http://dx.doi.org/10.3109/13880209.2013.775660] [PMID: 23746311]
[45]
Wang, C.Z.; Basila, D.; Aung, H.H.; Mehendale, S.R.; Chang, W.T.; McEntee, E.; Guan, X.; Yuan, C.S. Effects of ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model. Am. J. Chin. Med., 2005, 33(5), 807-815.
[http://dx.doi.org/10.1142/S0192415X05003429] [PMID: 16265993]
[46]
Cabezos, P.A.; Vera, G.; Castillo, M.; Fernández-Pujol, R.; Martín, M.I.; Abalo, R. Radiological study of gastrointestinal motor activity after acute cisplatin in the rat. Temporal relationship with pica. Auton. Neurosci., 2008, 141(1-2), 54-65.
[http://dx.doi.org/10.1016/j.autneu.2008.05.004] [PMID: 18579450]
[47]
Shin, Y.; Kim, B.; Kim, W. Cisplatin-induced nausea and vomiting: Effect of herbal medicines. Plants, 2022, 11(23), 3395.
[http://dx.doi.org/10.3390/plants11233395] [PMID: 36501434]
[48]
Spiller, R. Serotonin and GI clinical disorders. Neuropharmacology, 2008, 55(6), 1072-1080.
[http://dx.doi.org/10.1016/j.neuropharm.2008.07.016] [PMID: 18687345]
[49]
Vahora, I.S.; Tsouklidis, N.; Kumar, R.; Soni, R.; Khan, S. Correction: How serotonin level fluctuation affects the effectiveness of treatment in irritable bowel syndrome. Cureus, 2020, 12(9), c36.
[PMID: 32969414]
[50]
Höglund, E.; Øverli, Ø.; Winberg, S. Tryptophan metabolic pathways and brain serotonergic activity: A comparative review. Front. Endocrinol., 2019, 10, 158.
[http://dx.doi.org/10.3389/fendo.2019.00158] [PMID: 31024440]
[51]
Liu, N.; Sun, S.; Wang, P.; Sun, Y.; Hu, Q.; Wang, X. The mechanism of secretion and metabolism of gut-derived 5-hydroxytryptamine. Int. J. Mol. Sci., 2021, 22(15), 7931.
[http://dx.doi.org/10.3390/ijms22157931] [PMID: 34360695]
[52]
van lelyveld,; ter linde,; schipper,; samsom, Regional differences in expression of TPH-1, SERT, 5-HT 3 and 5-HT 4 receptors in the human stomach and duodenum. Neurogastroenterol. Motil., 2007, 19(5), 342-348.
[http://dx.doi.org/10.1111/j.1365-2982.2006.00891.x] [PMID: 17509016]
[53]
Betari, N.; Sahlholm, K.; Morató, X.; Godoy-Marín, H.; Jáuregui, O.; Teigen, K.; Ciruela, F.; Haavik, J. Inhibition of tryptophan hydroxyl-ases and monoamine oxidase-A by the proton pump inhibitor, omeprazole-in vitro and in vivo investigations. Front. Pharmacol., 2020, 11, 593416.
[http://dx.doi.org/10.3389/fphar.2020.593416] [PMID: 33324221]
[54]
Gershon, M.D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr. Opin. Endocrinol. Diabetes Obes., 2013, 20(1), 14-21.
[http://dx.doi.org/10.1097/MED.0b013e32835bc703] [PMID: 23222853]