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

doi:10.1016/S2095-4964(17)60327-3

Abstract

Objective

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.

Methods

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.

Results

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%.

Conclusion

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

Olasupo Stephen Adeniyi, James Omale, Samuel Chukwuma Omeje, Victoria Ojimaojo Edino. Antidiarrheal activity of hexane extract of Citrus limon peel in an experimental animal model. Journal of Integrative Medicine, 2017, 15(2): 158-164.

/ / Recommend

Add to citation manager EndNote| Reference Manager|ProCite|BibTeX|RefWorks

URL: http://www.jcimjournal.com/EN/10.1016/S2095-4964(17)60327-3

http://www.jcimjournal.com/EN/Y2017/V15/I2/158

TrendMD

References

1 1 World Health Organization. Health topics: diarrhoea. (2016) [2016-10-09]. 2016) [2016-10-09]. http://www.who.int/topics/diarrhoea/en/.
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]. http://www.newhealthguide.org/Eating-Lemon-Peel. 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.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Comments

Recommended 10

[1]	Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2]	Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3]	Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4]	Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5]	. Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6]	Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7]	Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8]	Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9]	Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10]	Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228

[1]	Si-qi Tang, Yun-liang Wang, Zi-ye Xie, Yang Zhang, Yi Guo, Kang-li Gao, Tang-you Mao, Chun-e Xie, Jun-xiang Li, Xiao-yan Gao. Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome. Journal of Integrative Medicine, 2021, 19(3): 274-281.
[2]	Khaled M. M. Koriem, Mahmoud S. Arbid, Hend N. Saleh . Antidiarrheal and protein conservative activities of Psidium guajava in diarrheal rats. Journal of Integrative Medicine, 2019, 17(1): 57-65.
[3]	Ali Khiveh, Mohammad Hashem Hashempur, Mehrdad Shakiba, Mohammad Hassan Lotfi, Afsaneh Shakeri, SeidKazem Kazemeini, Zohre Mousavi, Marzie Jabbari, Mohammad Kamalinejad, Majid Emtiazy. Effects of rhubarb (Rheum ribes L.) syrup on dysenteric diarrhea in children: A randomized, double-blind, placebo-controlled trial. Journal of Integrative Medicine, 2017, 15(5): 365-372.
[4]	Md. Asadujjaman, Ahmed Ullah Mishuk, Md. Aslam Hossain, Utpal Kumar Karmakar. Medicinal potential of Passiflora foetida L. plant extracts: Biological and pharmacological activities. Journal of Integrative Medicine, 2014, 12(2): 121-126.
[5]	Md. Khirul Islam, Imran Mahmud, Sanjib Saha, Asit Baron Sarker, Himangsu Mondal, A.S.M. Monjur-Al-Hossain, Md. Anisuzzman. Preliminary pharmacological evaluation of Alocasia indica Schott tuber. Journal of Chinese Integrative Medicine, 2013, 11(5): 343-351.
[6]	Sanjib Saha, Faroque Hossain, Md. Anisuzzman, Md. Khirul Islam. Pharmacological evaluation of Musa seminifera Lour. Fruit. Journal of Chinese Integrative Medicine, 2013, 11(4): 253-261.
[7]	Jing Li, Xin-lin Wu, Yuling Chen, Zhi Tang, Yue-hong Xu, Jian-min Jiang, Yue-yu Gu, Jian-ping Chen, De-po Yang, Dong-mei Wang. Antidiarrheal properties of different extracts of Chinese herbal medicine formula Bao-Xie-Ning. Journal of Chinese Integrative Medicine, 2013, 11(2): 125-134.
[8]	Sandhya Subhadra, Gouthami Gade, Vinod Kombath Ravindran, Vidya Sravanthi Emani, Saikumar Parre, David Banji. In vitro and in vivo evaluation of the inhibitory effect of Limnophila indica (Linn.) Druce on shigellosis. Journal of Chinese Integrative Medicine, 2012, 10(5): 538-545.
[9]	V. Patil Vikas, C. Bhangale Shandavi, J. Chaudhari Prashant, P. Chaudhari Kundan, T. Kakade Rajanikant, M. Thakare Vinod, G. Bonde Chandrakant, R. Patil Vijay. Evaluation of the antidiarrheal activity of the plant extracts of Ficus species. Journal of Chinese Integrative Medicine, 2012, 10(3): 347-352.
[10]	Khadem Ali Md., Ashraf Ayesha, Nath Biswas Nripendra, Kumar Karmakar Utpal, Afroz Shamima. Antinociceptive, anti-inflammatory and antidiarrheal activities of ethanolic calyx extract of Hibiscus sabdariffa Linn. (Malvaceae) in mice. Journal of Chinese Integrative Medicine, 2011, 9(6): 626-631.
[11]	Zhan-fan Liang, Ri-hui Chen, Yun-sheng Xu, Qing-xiang Chen, Mei-ling Dong. Tiaohe Ganpi Hexin Decoction in treatment of irritable bowel syndrome with diarrhea: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2009, 7(9): 819-822.