Antimotility,Antisecretory,Diarrhea,Lemon,Peel," /> Antimotility,Antisecretory,Diarrhea,Lemon,Peel,"/> Antidiarrheal activity of hexane extract of <em>Citrus limon</em> peel in an experimental animal model
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Journal of Integrative Medicine ›› 2017, Vol. 15 ›› Issue (2): 158-164.doi: 10.1016/S2095-4964(17)60327-3

Special Issue: Natural Drug

• Research Article • Previous Articles    

Antidiarrheal activity of hexane extract of Citrus limon peel in an experimental animal model

Olasupo Stephen Adeniyia, James Omaleb, Samuel Chukwuma Omejeb, Victoria Ojimaojo Edinob   

  1. a Department of Human Physiology, Faculty of Basic Medical Sciences, Kogi State University, Anyigba 272102, Nigeria 
    b Department of Biochemistry, Faculty of Natural Sciences, Kogi State University, Anyigba 272102, Nigeria
  • Received:2016-10-09 Accepted:2016-12-23 Online:2017-03-15 Published:2017-03-15
  • Contact: Olasupo Stephen Adeniyi; E-mail:


Acute diarrhea is one of the major illnesses that cause death in children, despite clinical interventions and the use of oral rehydration therapy. Thus, there is need to discover other effective, affordable and accessible treatments for this disease. Therefore, this study was carried out to investigate the effects of hexane extract of Citrus limon peel (HECLP) on castor oil-induced diarrhea in rats.


Diarrhea was induced in male albino Wistar rats weighing 100-150 g. The antidiarrheal activity of HECLP at different oral dosages (5, 10 and 20 mg/kg) was investigated by counting the number of wet fecal pellets. Animals were further treated with propranolol, prazosin, nifedipine and atropine to assess the effects of receptor blockers on the activities of the extract. The effects of HECLP on castor oil-induced enteropooling and the intestinal transit time of activated charcoal were also evaluated.


Each of the 3 doses of C. limon significantly reduced (P < 0.05) the number of wet fecal pellets produced by animals, with 20 mg/kg HECLP producing the highest percentage inhibition (34.2%). Wet fecal pellet inhibition by the standard drug loperamide (3 mg/kg p.o.) was 68.4% relative to the negative control. Blockage of β adrenergic receptors by propanolol abolished the antidiarrheal effects of HECLP. Intestinal fluid accumulation was inhibited by 68.7% and 78.5% by 20 mg/kg HECLP and loperamide respectively. Furthermore, 20 mg/kg HECLP significantly (P < 0.05) reduced the percentage intestinal transit time (21.4% ± 1.42%), relative to the control (34.2% ± 4.29%); atropine (5 mg/kg, intraperitoneal injection) significantly (P < 0.001) reduced the percentage intestinal transit time to 11.2% ± 0.85%.


These results suggest that C. limon peel possesses antidiarrheal effects through antisecretory and antimotility mechanisms that act through the β adrenergic system.

Key words: Antimotility, Antisecretory, Diarrhea, Lemon, Peel

1 1 World Health Organization. Health topics: diarrhoea. (2016) [2016-10-09]. 2016) [2016-10-09].
2 Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M, Mathers C, Black RE; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000.Lancet. 2012; 379(9832): 2151-2161.
3 Gerald TK, Olivier F, Alok B, Cynthia BP, Zulfiqar AB, Eduardo G, Juan R, Jeffrey C, Sonbol SS, Ramanan L.Disease control priorities in developing countries. 2nd ed. New York: Oxford University Press. 2006.
4 Boschi-Pinto C, Velebit L, Shibuya K.Estimating child mortality due to diarrhea in developing countries.Bull World Health Organ. 2008; 86(9): 710-717.
5 Terpstra AH, Lapre JA, de Vries HT, Beynen AC. The hypocholesterolemic effect of lemon peels, lemon pectin, and the waste stream material of lemon peels in hybrid F1B hamsters.Eur J Nutr. 2002; 41(1): 19-26.
6 Sridharan B, Michael ST, Arya R, Mohana Roopan S, Ganesh RN, Viswananathan P.Beneficial effect ofCitrus limon peel aqueous methanol extract on experimentally induced urolithic rats. Pharm Biol. 2016; 54(5): 759-769.
7 Naim M, Amjad FM, Sultana S, Isalm SN, Hossain MA, Begum R, Rashid MA, Amran MS.A comparative study of antidiabetic activity of hexane-extract of lemon peel (Limon citrus) and glimepiride in alloxan-induced diabetic rats. Bangladesh Pharm J. 2012; 15(2): 131-134.
8 8 New Health Guide. Eating lemon peel. (2014) [2016-05- 04]. 2014) [2016-05- 04]. html.
9 Neenu AS, Anto PV, Neethu BN.Evaluation on antimicrobial activity of fruit peels of selected citrus species against human pathogenic microorganisms.J Pharmacogn Phytochem. 2015; 4(3): 278-281.
10 Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O’Brien KL, Campbell H, Black RE. Global burden of childhood pneumonia and diarrhoea.Lancet. 2013; 381: 1405-1416.
11 Ezenwali MO, Njoku OU, Okoli CO.Studies on the antidiarrheal properties of seed extract ofMonodora tenuifolia. Int J Appl Res Nat Prod. 2010; 2(4): 20-26.
12 Teke GN, Kuiate JR, Ngouateu OB, Gatsing D.Antidiarrheal and antimicrobial activities ofEmilia Coccinea (Sims) G. Don extracts. J Ethnopharm. 2007; 112: 278-283.
13 Adeniyi OS, Akomolafe RO, Ojabo CO, Eru EU, Olaleye SB.Effect of zinc treatment on intestinal motility in experimentally induced diarrhea.Niger J Physiol Sci. 2014; 29: 11-15.
14 Inayathulla, Shariff WR, Karigar AA, Sikarwar MS. Evaluation of anti-diarrhoeal activity ofCrataeva nurvala root bark in experimental animals. Int J Pharm Pharm Sci. 2010; 2: 158-161.
15 Robert A, Nezamis JE, Lancaster C, Hanchar AJ, Klepper MS.Enteropooling assay: a test for diarrhea produced by prostaglandins.Prostaglandins. 1976; 11: 809-828.
16 Gamaliel KS, Akah PA.Analysis of the gastrointestinal relaxing effects of the stem bark extract ofGongronema latifolium. Phytomedicine. 1996; 2: 293-296.
17 Galvez J, Zarzuelo A, Crespo ME, Utrilla MP, Jiménez J, Spiessens C, de Witte P. Antidiarrhoeic activity ofScleroarya birrea back extract and its active tannin constituent in rats. Phytother Res. 1991; 5: 276-278.
18 Benet A, Sanger GJ.Acidic lipids: prostaglandins. Berlin: Springer-Verlag. 1982.
19 Luderer JR, Dermers LM, Nomides C, Hayes AH.Mechanism of castor oil: a biochemical link to the prostaglandins.Adv Prostaglandin Thromboxane Res. 1980; 8: 1633-1635.
20 Ohigashi H, Jisaka M, Takagaki T, Nozaki H, Tada T, Hufman MA, Nishida T, Kaji M, Koshimizu K.Bitter principle and a related steroid glucoside forVernonia amygdalina, a possible medicinal plant for wild chimpanzees. Agric Biol Chem. 1991; 65: 1201-1203.
21 Abdullahi AL, Agho MO, Amos S, Gamaniel KS, Wambebe C.Antidiarrhoeal activity of the aqueous extract ofTerminalia avicennoides roots. Phytother Res. 2001; 15: 431-434.
22 Synder JD, Merson MH.The magnitude of the global problem of acute diarrhoeal disease: a review of active surveillance data.Bull World Health Organ. 1982; 60: 605-613.
23 Hutton G, Haller L, Bartram J.Global cost-benefi t analysis of water supply and sanitation interventions.J Water Health. 2007; 5(4): 481-502.
24 Mohammed S, Tamiru D.The burden of diarrheal diseases among children under five years of age in Arba Minch District, Southern Ethiopia, and associated risk factors: a cross-sectional study.Int Sch Res Notices. 2014; 2014: 1-6.
25 Tenórioa JAB, do Monte DS, da Silva TMG, da Silva TG, Ramos CS.Solanum paniculatum root extract reduces diarrhea in rats. Rev Bras Farmacogn. 2016; 26(3): 375-378.
26 Sabiu S, Ashafa AOT.Antimicrobial and antidiarreal activities ofPelargonium luridum (Andrews) sweet root extract. Pharmacologia. 2016; 7: 202-210.
27 Okere OS, Sangodele JO, Tade OG, Obafemi OT, Falode JA.Antidiarrhea potential and acute toxicity studies of methanolic extract ofVernonia amygdalina and Cymbopogon citratus against castor oil induced diarrhea model in rats. Int J Biochem Res Rev. 2015; 6(2): 46-52.
28 Sharma DK, Gupta VK, Kumar S, Joshi V, Mandal RS, Prakash AG, Singh M.Evaluation of antidiarrheal activity of ethanolic extract ofHolarrhena antidysenterica seeds in rats. Vet World. 2015; 8(12): 1392-1395.
29 Ezeja IM, Ezeigbo II, Madubuike KG, Udeh NE, Ukweni IA, Akomas SC, Ifenkwe DC.Antidiarrheal activity ofPterocarpus erinaceus methanol leaf extract in experimentally induced diarrhea. Asian Pac J Trop Med. 2012; 5(2): 147-150.
30 Asrie AB, Abdelwuhab M, Shewamene Z, Gelayee DA, Adinew GM, Birru EM.Antidiarrheal activity of methanolic extract of the root bark ofCordia africana. J Exp Pharmacol. 2016; 8: 53-59.
31 Rahman K, Chowdhury AU, Islam MT, Chowdhury A, Uddin ME, Sumi CD.Evaluation of antidiarrheal activity of methanolic extract ofMaranta arundinacea Linn. leaves. Adv Pharmacol Sci. 2015; 2015: 257057.
32 Rajput MS, Nair V, Chauhan A, Jawanjal H, Dange V.Evaluation of antidiarrheal activity of aerial parts ofVinca major in experimental animals. Middle East J Sci Res. 2011; 7(5): 784-788.
33 Laloo D, Hemalatha S.Ethnomedicinal plants used for diarrhea by tribals of Meghalaya, Northeast India.Pharmacogn Rev. 2011; 5(10): 147-154.
34 Ouyang H, Chen JD.Review article: therapeutic roles of acupuncture in functional gastrointestinal disorders.Aliment Pharmacol Ther. 2004; 20(8): 831-841.
35 Doherty NS, Hancock AA.Role of alpha-2 adrenergic receptors in the control of diarrhea and intestinal motility.J Pharmacol Exp Ther. 1983; 225(2): 269-74.
36 Akomolafe RO, Adeoshun IO, Ayoka AO, Elujoba AA, Iwalewa EO.Anin vitro study of the effects of Cassia podocarpa fruit on the intestinal motility of rats. Phytomed. 2004; 11(2-3): 249-254.
37 Mohammed A, Ahmed H, Goji ADT, Okpanachi AO, Ezekiel I, Tanko Y.Preliminary anti-diarrhoeal activity of hydromethanolic extract of aerial part ofIndigofera pulchra in rodents. Asian J Med Sci. 2009; 1(2): 22-25.
38 Wendel GH, Teves MR, Paredes JD, Sánchez Perera LM, Pelzer LE.Evaluation of the antidiarrheal activity of Rhizophora mangle L.(Rhizophoraceae).Lat Am J Pharm. 2013; 32(1): 128-131.
39 Bornstein JC, Furness JB.Correlated electrophysiological and histochemical studies of submucous neurons and their contribution to understanding enteric neural circuits. J Auton Nerv Syst.1988; 25: 1-13.
40 Lundgren O.Sympathetic input into the enteric nervous system.Gut. 2000; 4(47): 33-35.
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