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World Academy of Science, Engineering and Technology International Journal of Medical Science and Engineering Vol:7 No:11, 2013 (Amorphophallus muelleri Blume) in Treatment of Loperamide Induced Constipation on Sprague Dawley Simon Bambang Widjanarko, Novita Wijayanti, Aji Sutrisno Laxatives drugs are agents that add bulk to intestinal Abstract—There is long history of konjac tubers being used as a
contents, that retain water within the bowel lumen by virtue of cure for certain diseases in China and Japan. Konjac flour is prepared osmotic effects, or that stimulate intestinal secretion or from konjac tubers and it contains high concentration of motility, thereby increasing the frequency and ease of glucomannan. Konjac Glucomannan (KGM) is dietary fiber and the defecation [5]. There are four main types of laxative drug: role of which has been demonstrated in weight reduction, lowering bulking agents, stool softeners, stimulant laxatives and blood cholesterol and sugar level, promoting intestinal activity etc. Konjac glucomanan has a property of swelling by absorbing water, osmotic ally active compounds [6]. The use of laxative drug is more than a hundred times its own weight. Therefore it helps very common for constipation treatment especially for older increasing weight of feces, water content of feces, and promotes people. But, repeated use of laxative drugs has side effects. satiety feeling. Mode of actions of dietary fibre as laxatives agents Senna (anthraquinones) can cause allergic reactions, fluid and includes holding water inside the bowel lumen, inhibition of water electrolyte depletion, and Melanesia coli. The side effect of absorption in the colon and stimulating colonic motility. Number of bulking agents was bloating and flatulence depends on their fecal pellets did not effected in rats were fed on 300 and 600 mg/kg of konjac flour, as well as constipated control and Dulcolax doses. Diphenylmethane derivatives (bisacodyl) may cause treatment. Water content, weight of fecal pellets and gastrointestinal cramping and electrolyte depletion when large doses are used. transit ratio were higher in rats treated with 600 mg/kg than 300 Diarrhea is a side effect of colchicine drug [5]. mg/kg of konjac flour. Rats were administered with Dulcolax showed Side effects of the laxative drug encourage the research to the highest gastrointestinal transit ratio, followed by 600 mg/kg find safer compound without side effects and derived from konjac flour. The lowest feed consumption was noted in 600 mg/kg plants. Several researches reported that many plant could use as laxative agents, such as: apple fruit [7], figs fruit [8], kiwi Keywords—Laxative, konjac flour, Amorphophallus muelleri fruit [9], [10], papaya fruit [11], watermelon fruit [12],
flaxseed [13], Aloe ferox Mill leaves [14], Aloe vera leaves [15], tamarind leaves [16], agarwood leaves [17], [18], euphorbiaceae leaf [19] and konjac tubers [20]. ONSTIPATION is a common problem in public health Konjac glucomannan (KGM) is a dietary fiber that derived C related with infrequency, difficulty or discomfort of from Amorphophallus konjac. It has been shown to relieve defecation process and sense of incomplete evacuation, which constipation, which could be associated with increased stool marked with feces remain in the colon for prolonged periods bulk and improved colonic ecology [21]. Several researches of time, leading to water absorption, hardening of stool and also reported that konjac flour that contains glucomannan can excessive straining [1]. An epidemiologic study of used as laxative agent for children, pregnant women, and constipation in the United State identified it as an inability to healthy man. Reference [22] found that glucomannan to be evacuate feces completely and spontaneously three or more beneficial in the treatment of constipation in children with no times per week [2]. Several conditions such as deficiency of significant side effects such as: abdominal pain, bloating, dietary fiber, fluid, exercise, metabolic problem, increase use abdominal distention, excessive gas, diarrhea, or anaphylactic of medication and age can cause constipation. Constipation symptoms. Reference [23] reported that consumption of 1.45 generally first appears between the ages of two and four years grams per day of glucomannan in constipated pregnant women children. Up to one third of children ages 6 to 12 years report for 1-3 months induced a return to normal frequency of constipation [3]. Constipation is also common in older people weekly number of evacuations (4.9-5.8 times/weeks). and the number of persons reporting constipation increases Moreover, supplementation of konjac glucomannan (4.5 gram per day) into low-fiber diets increased bowel movement frequency by 30% and improved the colonic ecology in                                                              Simon Bambang Widjanarko, Novita Wijayanti, and Aji Sutrisno are with Konjac flour which has been reported as a laxative agent the Department of Agricultural Product Technology, Faculty of Agricultural was konjac glucomannan that originated from Japan Technology, University of Brawijaya, Jalan Veteran, Malang 64145(Contact (Amorphophallus konjac). In fact, there are another species of World Academy of Science, Engineering and Technology International Journal of Medical Science and Engineering Vol:7 No:11, 2013 konjac (Amorphophallus muelleri Blume) that have a high F. Total Number, Dry Weight and Water Content of the potential and prospects for development in Indonesia [25]. Therefore, this research will be conducted to determine the The excreted fecal pellets of individual rats were collected effect of konjac flour from Indonesia as laxative drug. everyday at 15:00 throughout the duration of the experiment. Therefore this paper is, to report the laxative effect of konjac Total number, weight and water content of the fecal pellets flour on loperamide-induced constipation rats. The konjac were determined and data taken from the average value of five flour from Amorphophallus muelleri Blume was extracted by days assessment. The water content was calculated as the using multi-stage maceration method with ethanol solvent at difference between the wet and dry weight on the pellet. G. Gastrointestinal Transit Ratio Gastrointestinal transit ratio was measured according to the method in [16]. Before measurement of GIT ratio, rats were fasted for 18 hours but they allowed free access of water. The tubers of konjac (Amorphophallus muelleri Blume) Then, the rats were fed a standard diet. After 45 minutes, 1ml were thoroughly washed with water, cut into thin slices and of norit (3 gram suspended in 25ml of water) was orally dried in the oven at 40oC for 24 hours. The dried chips were administered to the rats as a marker. 20 minutes after grinded into powder with stamp mill for 16 hours, 30 minutes, administering the marker, the animals were anesthetized and 24 second at frequency 18.47. Then, konjac flour was sieved sacrificed. The abdomen immediately cut open to excise the at 30 meshes and blower by using air classifier. 25 gram of whole small intestine. The small intestine from the pylorus to materials was purified by multi stage maceration method with the caecum was quickly removed and the distance traveled by 233.77 ml ethanol 40%, 60% and 80% respectively, at 434.22 the norit and the total length of the intestine were measured. rpm for 4 hours, 16 minutes. Then, it was filtered by a filter The GIT ratio was expressed as the percentage of the distance paper and the precipitate was dried in an oven at 40oC for 24 travelled by the norit relative to the total length of the small Male albino rats (Rattus norvegicus) of Sprague Dawley Data are presented as mean ± standard deviation of three strain with a mean weight 175-250 gram. The animals were replicates and were subjected to one way analysis of variance housed individually in plastic cage placed in a well ventilated (ANOVA) followed by Tukey’s Honestly Significant house with optimum condition. They were acclimatized to the Difference (HSD) test to determine significant differences in animal house condition for 7 days during which they were all parameters. Values were considered statistically significant allowed free access to standard diet (AIN-93M) and tap water All experiment procedures were approved by the Ethical Clearance Committee, University of Brawijaya, Malang, To evaluate the laxative effect of konjac flour from Amorphophallus muelleri Blume, groups of rats were induction with loperamide 3mg/kg body weight for three days, D. Induction and Evaluation of Constipation except one group for normal control. After induction time, all Constipation was induced in the animals by the oral the groups of rats were fed with diet containing konjac flour administration of 1ml loperamide (3mg/kg body weight in with the doses based on experimental design and also water for 3 days), while the normal control were administered Dulcolax as a laxative drug control. The weight of feed intake with the water only. The passage of reduced, hard and dry and water intake was significantly reduced in constipated rat fecal pellets indicated constipation in the rats. The rats were grouped into five of three rats each, the EFFECT OF KONJAC FLOUR OF FEED INTAKE AND WATER INTAKE animals in group 1 (normal control) and group 2 (constipated control) were not administered with konjac flour. Group 3 and 4 comprised constipated rats given 300 and 600 mg/kg body weight/day of konjac flour respectively, while group 5 were constipated rats administered with 0.75 mg/kg body weight of Bisacodyl (Dulcolax). The water intake and feed intake of all the rats were recorded during experiment period and treatment Data are means ± SD (n=3): different letters from the control are continued for 5 days. Then, the gastrointestinal transit ratio measurement was assessed on the sixth day. Based on Table I, normal control group had the highest value of feed intake and significant different compare with World Academy of Science, Engineering and Technology International Journal of Medical Science and Engineering Vol:7 No:11, 2013 other control group. Addition of konjac flour doses had a C. Gastrointestinal Transit Ratio tendency to reduce feed intake of constipated rats. Meanwhile, the water intake was highest in normal control group, but it had a different trend compare with feed intake parameter. This is due to the increased dosage of konjac flour would increase water consumption of constipated rats although there were no significant difference amongst konjac flour diet group (P<0.05). These result indicated that the administering of loperamide affected on feed and water intake. In the control group, loperamide administration Fig. 1 Data is gastrointestinal transit ratio in normal, loperamide- significantly decreased the number of fecal weight and fecal induced rats + konjac flour and loperamide-induced rats + dulcolax- water content, suggesting the induction of loperamide-induced treated rats. Data are mean of three determination ± standard constipation (P<0.05). In the meantime, the number fecal deviation bars with different letters from the control are significantly pellet was no significant difference between control groups. It indicated that the administering of loperamide was not effect of number fecal pellet. Oral administration of loperamide (3mg/kg body weight) for three days induced constipation on normal rats by EFFECT OF KONJAC FLOUR ON FECAL PROPERTIES OF RATS decreasing of fecal pellet weight and water content. This is related to that loperamide enhances absorption of water, electrolytes, and glucose from an isotonic buffer containing glucose, and partially reversed the effects of PGE2 (prostaglandin E2) on water and electrolytes transport. PGE2 induced secretion of fluid in the rat intestinal tract and its action might be related to an effect on intestinal motility [27]. Data are means ± SD (n=3): different letters from the control are significantly reduced that secretion [28]. The drug also In the constipated groups, when the konjac flour content in suppresses the peristaltic contraction caused by distension of diet was increased, the water content and weight of fecal pellet the intestinal lumen [29]. Moreover, loperamide may reverse increased dose-dependently, the increase being significant the elevation of hydrostatic tissue pressure that opposes with the dose 600 mg/kg body weight in comparison with the normal absorption, when secretory stimuli increase mucosal constipated control group (P<0.05). Moreover, in the dose 600 tension. This anti secretory effect at the mucosal is mg/kg of konjac flour was the highest in fecal water content accompanied by motor effects when loperamide reaches the following with normal control group [Table II]. These result mesenteric muopiate receptors [30]. The reduction in the water indicated that administration of 600 mg/kg of konjac flour consumed by the constipated animals may also be due to the could relieved constipation by increased of water content of effect of the drug which probably accounted for the reduction fecal in comparison with Dulcolax (laxative drug). in water content of the fecal pellets [14]. Loperamide administration reduced the gastrointestinal The administration of konjac flour of Amorphophallus motility in the untreated constipated rats [Fig. 1]. It was noted muelleri Blume to the constipated rats was effective in that no significant difference of ratio was observed between influencing increased water content, weight of fecal pellet and the constipated control and the normal control. It showed that intestinal motility. These are indication of the laxative the administering of loperamide had no effect on the property of the plant. This may be due to the high gastrointestinal transit ratio. The konjac flour diet increased concentration of glucomannan as dietary fiber. Konjac the gastrointestinal transit ratio with the increasing of the glucomanan has a property of swelling, by absorbing 138-doses. Especially for the dose 600 mg/kg of konjac flour, the 200% of water [31]. Hence, konjac have beneficial effect to treatment of konjac flour increased the gastrointestinal relieve constipation because of its capacity to absorb and movement which compared with Dulcolax, a standard laxative High content of dietary fiber on diet relates to fecal consistency, because fecal consistency depends on the ratio of the water holding capacity of the insoluble solids, such as dietary fibers. When there are sufficient water holding solids or little no bound water, stools remain thick or formed. On the other hand, if there are too few of these water holding solids to bind all of the water present, stool consistency becomes loose, eventually to the point of being like water [32]. World Academy of Science, Engineering and Technology International Journal of Medical Science and Engineering Vol:7 No:11, 2013 Dietary fiber is fermented by micro flora in the colon. The result of this is to stimulate microbial growth and to increase This research was supported by Directorate General of microbial mass [33]. The additional mass in the colon that Higher Education through the Minister of National Education occurs with adequate fiber diets eases distal propulsion of and Culture, Republic of Indonesia, which has provided by a luminal contents, and this decreased transit time means less research funding support, through the University of Brawijaya time for interaction between the enterocyte and luminal DIPA No. 0636/023-04.2.16/15/2012 on December 9, 2011 contents [34]. Dietary fiber fermentation by micro flora was and by Rector decree of the University of Brawijaya No. also to lead the production of SCFAs that lower colonic pH and result in a significant prebiotic effect in which the growth of beneficial intestinal micro flora. 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CURRICULUM VITAE Surgical Treatment of Bone and Soft Tissue Tumors, Biomedical Sciences Cancer Biology EDUCATION MD: Medical Faculty of Zurich, Switzerland, 1992 MD: United States Medical Licensing Examination USMLE 1997 PhD: Biomedical Sciences, Tumor Biology, Mayo Graduate School, Mayo College of Medicine, Rochester, MN, USA, 2004 Residency in General Surgery and Neurosurgery (

Doi:10.1016/j.ijantimicag.2009.08.009

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