Introduction: Acute diarrhea is one of the most important causes of global childhood mortality and morbidity. The most common complication of acute diarrhea is dehydration. The aim of this study was to evaluate the use of aqueous Elaeagnus angustifolia extract in controlling non-inflammatory diarrhea in a hospital setting.  Methods: In this case&ndash;controlled randomized double blind clinical trial 80 children in age range of 1-5 years were admitted in pediatric ward with diagnosis of non-inflammatory diarrhea. The patients were randomly divided into two equal groups of 40 cases. The subject in the first group received aqueous Elaeagnus angustifolia extract, 1.2 ml/Kg single dose for 4 days duration and the second group (control group) 1.2 cm/Kg distilled water single dose for 4 days duration. Data analysis were performed by Chi-square and t-tests, using SPSS software.  Results: The groups were similar regarding gender, mean age, and frequency, and consistency of defecation (p&gt; 0.05). Although the children seemed better in regard to frequency and consistency of defecation, however the results showed that aqueous extract of Elaeagnus angustifolia was not significantly effective in the treatment of non-inflammatory diarrhea.  Conclusion: The results of this study demonstrated that the use of aqueous extract of Elaeagnus angustifolia was not effective in the treatment of non-inflammatory diarrhea in children.</p

Famuri, Fatemeh.

Kasiri, Karamali.

Keivani, Elham.

Khoshdel, Abolfazl.

Lotfizadeh Dehkordi, Masoud.

Rafieian, Morteza.

shahrekord university of medical scinces

Journal of HerbMed PharmacologyJournal homepage: http://www.herbmedpharmacol.com                J HerbMed Pharmacol. 2014; 3(1): 53-56.The effect of aqueous Elaeagnus angustifolia extract on acute non-inflammatory diarrhea in 1-5 year old children*Corresponding author: Abofazl Khoshdel, Email: Nikakhosh@gmail.com Introduction Acute gastroenteritis is a major cause of mortality and morbidity in the world so that more than 2.5 million deaths are reported annually in children younger than five years (1). It is often caused by an infection. Rotavirus causes 75 to 90% of diarrhea infections in children. Bacterial pathogens cause another 10 to 20% and parasites cause less than 5% of infections (2). Acute gastroenteritis in children is presented with or without abdominal pain, fever, nausea or vomiting (3). It is the major cause of hospitalization in children under age of five (1). Diarrhea is usually defined as increase in vomiting or fluidity of stool, change in consistency, and increased frequency of defecation. World health organization (WHO) defines diarrhea as the passage of loose or watery stools at least three times in 24 hours period but this definition emphasizes the important of change in stool consistency rather than frequency (4). Diarrhea disorder can be divided into inflammatory and non-inflammatory ones (5). Inflammatory diarrhea causes bloody stools that are usually full of white blood cells. It involves the large intestine, and may be accompanied by fever, vomiting and colicky abdominal pain or tenderness. But, non inflammatory diarrhea is watery without blood and mucus and usually without fever (6). It often involves small bowel and does not cause destruction of mucosa (7). Abofazl Khoshdel1*, Fatemeh Famuri2, Elham keivani3, Masoud Lotfizadeh2, Karam-Ali Kasiri2, Mortaza Rafieian41Clinical Biochemistry Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran2Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran3Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran4Isfahan Governor Office, Isfahan, IranImplication for health policy/practice/research/medical education:The results of this study demonstrated that the use of aqueous extract of Elaeagnus angustifolia might not be significantly beneficial in the treatment of non-inflammatory diarrhea.Please cite this paper as: Khoshdel A, Famuri F, Keivani E, Lotfizadeh M, Kasiri KA, Rafieian M. The effect of aqueous Elaeagnus angustifolia extract on acute non–inflammatory diarrhea in 1-5 year old children. J HerbMed Pharmacol. 2014; 3(1): 53-56.Introduction: Acute diarrhea is one of the most important causes of global childhood mortality and morbidity. The most common complication of acute diarrhea is dehydration. The aim of this study was to evaluate the use of aqueous Elaeagnus angustifolia extract in controlling non-inflammatory diarrhea in a hospital setting. Methods: In this case–controlled randomized double blind clinical trial 80 children in age range of 1-5 years were admitted in pediatric ward with diagnosis of non-inflammatory diarrhea. The patients were randomly divided into two equal groups of 40 cases. The subject in the first group received aqueous Elaeagnus angustifolia extract, 1.2 ml/Kg single dose for 4 days duration and the second group (control group) 1.2 cm/Kg distilled water single dose for 4 days duration. Data analysis were performed by Chi-square and t-tests, using SPSS software. Results: The groups were similar regarding gender, mean age, and frequency, and consistency of defecation (p> 0.05). Although the children seemed better in regard to frequency and consistency of defecation, however the results showed that aqueous extract of Elaeagnus angustifolia was not significantly effective in the treatment of non-inflammatory diarrhea. Conclusion: The results of this study demonstrated that the use of aqueous extract of Elaeagnus angustifolia was not effective in the treatment of non-inflammatory diarrhea in children. A R T I C L E  I N F OKeywords:Aqueous extractDiarrheaNon-inflammatory diarrheaChildrenElaeagnus angustifoliaMedical plantsArticle History:Received: 2 May 2014Accepted: 21 May 2014ePublished: 1 June 2014Article Type:Original ArticleA B S T R A C Tkhoshdel A et al.Journal of HerbMed Pharmacology, Volume 3, Number 1, June 2014 http://www.herbmedpharmacol.com 54Management of non-inflammatory diarrhea is supportive until the mucosa heals. This support includes fluid therapy and preventing nutritional damage (8). Medical plants have been used for the management of various conditions for thousands of years (9). Elaeagnus angustifolia (Russian olive, Oleander) is one of the traditional medicines used in the management of diarrhea (9).  In herbal medicine oleaster fruit or flower extract are used for management of nausea, vomiting, asthma and flatulence (10). Extract of Elaeagnus (E) angustifolia is used as anti-inflammatory agent, muscular relaxant, antiulcerogenic agent and antipyretic in traditional medicine (11-14). In Iranian traditional medicine, fruit of E. angustifolia have been used to relief pain in patients with rheumatoid arthritis (14). Also, it has been reported that the use of the fruit of E. angustifolia is beneficial in the treatment of dysentery and diarrhea (15). In this research we evaluated the effect of aqueous E, angustifolia extract on non-inflammatory diarrhea in 1-5 age group children. Materials and Methods In this experimental double blind randomized clinical trial 80 children with non-inflammatory diarrhea were divided into two equal groups. The study was conducted in Pediatric ward of Hajar hospital in Shahrekord, Iran, during the period from September 2013 to May 2014. The study protocol was approved by the Ethical Committee of Shahrekord University of Medical Sciences, Iran. Written informed consents were obtained from all parents of children. The children with severe diarrhea, chronic diarrhea and/or intractable vomiting were excluded from the study. For preparation of the aqueous extract of E. angustifolia 150 grams of E. angustifolia with cores were grinded and added 1200 ml of distilled water. The resulting solution was boiled for 20 minutes. When the volume of the solution reached to one liter, the solution was filtered after cooling. The extract was frozen in –20 °C. Placebo was made of distill water in syringes, the same as the extract. After preparation, one code was given for placebo and other code was given to drug by a third person.For diagnosis of non-inflammatory diarrhea, stool exam was done for all the patients. This study was double blind in which the code of the drug or placebo was undefined for the patients or their parents, as well as for the doctor. In case group aqueous extract of E. angustifolia with dose of 1.2 ml/Kg, one time per day, was used for 4 days. In control group, the same volume of distilled water was used as placebo. Demographic data, frequency, volume and consistency of stool of both groups were recorded in first and fifth days of admission. The data were analyze using SPSS software, by Chi square and t-tests. Results In this study 80 children were enrolled and entered the trial. Seventeen children (8 subjects from the control group and 9 subjects from the case group) were excluded from the study because of non-compliance. The mean age in the study population was 18.65±9.13 years. The mean age in case group was 19.43±10.6 and in control group was 17.83±7.3 years. The mean weight in the study population was 10.76±2.01 Kg (10.93±2.07 Kg, in case group and 10.59 ±1.9 Kg, in control group) (p>0.05; Table 1). The mean frequency of defecation in case group before E. angustifolia usage was 8.5 ± 4 times and after usage, it was 3.5±1.84 times and in control group it was 7.6±3.5 times and 3.4±2, respectively. Statistical analysis showed no significant difference in decrease of frequency of defecation between the two groups (p>0.05; Table 2). Also, there was no difference in decrease of volume and consistency of stool in two groups (p>0.05; Table 3). Table 1. Demographic information of study populationWeight (Kg) Age (month)GenderTotal Case Control Total Case ControlMean 10.76 10.93 10.59 18.65 19.43 17.83 -Std. Deviation 2.01 2.07 1.9 9.13 1.06 7.3 -Minimum 7 7 8 12 12 12 -Maximum 16 15 16 60 60 50 -P-value (Case & Control) 0.63 0.49 0.06Table 2. Frequency of defecationGroupStool (first visit) Stool (second visit)Mean Std. DeviationMinimum Maximum P-value Mean Std. DeviationMinimum Maximum P-value8.5 4 4 200.373.5 1.84 4 160.727.6 3.5 4 16 3.4 2 1 9Effect of Elaeagnus angustifolia on acute non-inflammatory diarrheaJournal of HerbMed Pharmacology, Volume 3, Number 1, June 2014http://www.herbmedpharmacol.com 55Discussion Despite widespread use of oral rehydration therapy (ORT) and an increased understanding of the pathogenesis of diarrhea, the illness has still high mortality, especially in developing countries (16). In folk medicine E. angustifolia has been used for diarrhea. The results of this study indicated that aqueous extract of E. angustifolia had no effect in improvement of consistency of stool and decreased volume, as well as the frequency of defecation in children with non-inflammatory diarrhea. The findings of current study are in consistent with those of a previous study which reported that this drug had no effect in decrease of consistency of mice stool (17). In one study, Galves et al. (18) showed that tannins of the E. angustifolia decreased motility of gastrointestinal tract of mice and decreased volume of defecation in mice with diarrhea. The discrepancy of this study with our results may be due to the usage of one of the ingredients of E. angustifolia but in our study all of components in aqueous extract were used.  Also, in another study lactoferrin of E. angustifolia had good effect in the treatment of diarrhea (19). But in this study all of the patients had diarrhea with iron deficiency anemia and this improvement probably was due to improvement of anemia. In Rozhon study on mice infected with vibrio cholera showed that procyanidin, one of the ingredients of E. angustifolia was effective in diarrhea (20), but in our study we did not examine specific pathogen and a wide range of viral and bacterial infections that cause non-inflammatory diarrhea were included. In a study in patients with allergic rhinitis, intradermal injection of extract of E. angustifolia caused positive skin test (21). Therefore, children with non-inflammatory diarrhea and simultaneously food allergy might get no beneficial effects and even worsen their conditions. Authors’ contributionsAll the authors wrote the manuscript equally.Conflict of interestsThe authors declared no competing interests.Ethical considerations Ethical issues (including plagiarism, misconduct, data fabrication, falsification, double publication or submission, redundancy) have been completely observed by the authors. Funding/SupportNone.References 1. Walker WA. Pediatric gastrointestinal disease. 3rd edition. Hamilton, Ontario: BC Decker;2000. 2. Acute Gastroenteritis Guideline Team, Cincinnati Childrens Hospital Medical Center. Evidence–based care guideline for prevention and management of acute gastroenteritis in children age 2 months to 18 years. [updated December 21, 2011; Accessed January 20, 2012]. Available from: http://www.Cincinnatichildrence.org/service/j/Anderson–center/evidence–based–care/gastroenteritis/ 3. Children Mercy Hospitals and Clinics, Kansas City. Acute gastroenteritis (AGE) clinical practice guideline. Accessed July 11, 2010. Available from: http://www.childrensmercy.org/content/view.aspx?id=89904. World Health Organization. The treatment of diarrhea: A manual for physicians and other senior health workers, WHO/CDR/95.3. Geneva: WHO; 1995. 5. World Health Organization. The management of bloody diarrhea in young children: WHO/CDD/94.49. Geneva: WHO; 1994. 6. World Health Organization. Persistent diarrhea in children: CCD/DDM/85.1. Diarrheal disease control. Geneva: WHO; 1985. 7. Udayakumar N, Ralph AG. Mechanisms of infectious diarrhea. Nat Rev Gastroenterol Hepatol 2008; 5: 637-647.8. Centers for Disease Control and Prevention. Managing acute gastroenteritis among children: Oral rehydration, maintenance, and nutritional therapy. MMWR Morb Mortal Weekly Rep 2003; 52: 1-13. 9. Ramezani M, Hosseinzadeh H, Daneshmand N. Antinociceptive effect of Elaeagnus angustifolia fruit seeds in mice. Fitoterapia  2001; 72(3): 255-62. 10. Mirheydar H. Encyclopedia of plants: Indications of plants in the prevention and treatment of diseases, Vol. 2. Tehran: Islamic Farhang Press; 1998. p.163-4 . 11. Ahmadiani A, Hosseiny J, Semnanian S, Javan M, Saeedi F, Kamalinejad M, et al. Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit extract. J Ethnopharmacol 2000; 72(1- 2): 287- 92. 12. Hosseinzadeh H, Ramezani M, Namjo N. Muscle relaxant activity of Elaeagnus angustifolia L. Fruit seeds in mice. J Ethnopharmacol 2003; 84 (2-3): 275–8.Table 3. Percent of recovery following drug or placebo consumptionComplete recovery Relative recovery Without recovery (no change) p-valueExtract  group 62.5% 34.4% 3.1%0.31Control group 51.6% 41.9% 6.5%khoshdel A et al.Journal of HerbMed Pharmacology, Volume 3, Number 1, June 2014 http://www.herbmedpharmacol.com 5613. Gurbuz I, Ustum O, Yesilada E, Sezik E, Kutsal O. Antiulcerogenic activity of some plants used as folk remedy in Turkey. J Ethnopharmacol 2003;88(1): 93–7. 14. Farahbakhsh S, Arbabian S, Emami F, Rastegar-Moghadam B, Ghoshooni H. Inhibition of cyclooxygenase type 1 and 2 enzyme by aqueous extract of Elaeagnus angustifolia in mice. Basic Clin Neurosci  2011;2(2):31-7. 15. Lev E, Amar Z. Ethnopharmacological survey of traditional drugs sold in the Kingdom of Jordan. J Ethnopharmacol 2002;82:131-145. 16. Nikhil T, Lan RS. Diarrhoea in children: an interface between developing and developed countries. Lancet 2004;21:(363):641-652 . 17. Ganan ZH, Zhihua H, Yaxian W. An inquiry in to preparing diarrhea model of mice and application of diarrhea index. Chinese Trad Herb Drugs 1994;4. 18. Galvez J, Zarzulo A, Cresp ME. Anti diarrhoeic activity of sclerocarya birrea bark extract and its active tannin constituent in rats. Pharmacol Pharmacent Med 1991; 5 (6): 276-278. 19. Delia R, Huang B, Huang J. Recombinant human laectoferin treatment for global health issue: Iron deficient and acute diarrhea. Biometals 2004; 17: 337- 342. 20. Rozhan EJ, Khandwala AS, Sabouni A. Method of threating secretory diarrhea with enteric formulations of pro-anthocyanidin polymer. Google Patents, 2008.21. Kernerman SM, Mccullough J, Green J. Evidence of cross- reactivity between olive, ash, privet, and Russian olive tree pollen allergens. Ann Allergy 1992;69(6): 493-496.

The effect of aqueous Elaeagnus angustifolia extract on acute non-inflammatory diarrhea in 1-5 year old children

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