Indo American Journal of Pharmaceutical Research, 2016

ISSN NO: 2231-6876

HERB-DRUG INTERACTION BETWEEN ETHANOLIC EXTRACT OF ALOE VERA WITH GLIPIZIDE IN STREPTOZOTACIN INDUCED DIABETIC RATS P. Naveen, J. Padma, Dr. B. Vasudha, Dr. T. Shivaraj Gouda* Department of Pharmacology, School of Pharmacy, Anurag group of institutions Hyderabad. * NET College of Pharmacy, Raichur, Karnataka. ARTICLE INFO Article history Received 21/01/2016 Available online 10/02/2016 Keywords Herb-Drug Interaction, Aloe Vera, Glipizide, Synergistic Effect.

ABSTRACT Objective: To evaluate herb drug interaction between ethanolic extract of Aloe vera with glipizide in streptozotacin induced diabetic rats. Methods: The streptozotacin induced diabetic rats were treated with ethanolic extract of Aloe vera at selective doses (20, 40 and 80 mg/200g, p.o), glipizide (0.18mg/200g, p.o) and combination of high dose (80 mg/200g, p.o) of ethanolic extract of Aloe vera and glipizide. The Blood glucose level was estimated at 0, 7, 14, 21 and 28 days. Body weight of the rats of all the groups was recorded before and after the study period of 28 days. Results: Significant hypoglycemic effect observed in ethanolic extract of Aloe vera and glipizide treated groups. The decreased blood glucose levels were observed higher in combination of drug treatment group than single administration groups, and body weight also improved significantly in streptozotocin induced diabetic rats. Conclusion: The results clearly revealed ethanolic extract of Aloe vera augments the hypoglycemic effect of glipizide in streptozotacin induced diabetic rats. Further studies are recommended for clinical benefits in humans to reduce the glipizide dose and avoid the adverse effect of glipizide.

Copy right © 2016 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Please cite this article in press as Pathakala Naveen et al. Herb-Drug Interaction between Ethanolic Extract of Aloe Vera with Glipizide in Streptozotacin Induced Diabetic Rats. Indo American Journal of Pharmaceutical Research.2016:6(01).

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Corresponding author Pathakala Naveen Asst.Professor Department of Pharmacology School of Pharmacy Anurag Group of Institutions, Hyderabad [email protected]

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INTRODUCTION Herb drug interactions are hot research area worldwide in present trend. Trend is going back to classical usage of herbal remedies for various disease treatments instead of allopathic medication. It is because of people trust herbal drugs are safe, easily available as over the counter drugs and cheaper in price. Some patients are consumed prescribed allopathic medication and non prescribed herbal drugs together for fast alleviation from disease incidence. These might be chance of getting interaction between allopathic medication and herbal drug. The increasing popularity of alternative therapies, including herbal remedies is a new challenge for health care providers because the evidence on safety for herbal remedies incomplete, complex and confusing. The herbal medicines are certainly associated with risks and benefits. Interaction between herbal medicines and drugs are based on the same pharmacokinetic and pharmacodynamic principles as like drug-drug interactions. [1] The concomitant use of herbs and drugs is a growing trend especially in the elderly and management of chronic ailments. Most of the chronic diseases are difficult to treat successfully with orthodox drugs. Combination of herbs and drugs are useful to treat these chronic diseases. Diabetes mellitus is one of the most famous and wide spread diseases. It is a group of metabolic disorder characterized by hyperglycemia resulting defects in insulin secretion, insulin action or both. [2, 3] Aloe vera has been used in folk medicine as a remedy for various diseases. Aloe vera gel obtained from the inner portions of the leaves contains glucomannans (Mannose Phosphate, beta 1, 4 acetylated mannan, Alprogengluco protein and c-glucosylchromone) which is account for hypoglycemic effect (Shane et al., 2001). Glipizide is one of the novel class of anti-diabetic drug which is widely prescribed by physicians. Most of the people now a day taking Aloe juice daily, so it may affect the hypoglycemic action of Glipizide. In view of the above features the present study was planned to check the possibility of pharmacodynamics interaction between Aloe vera and Glipizide. MATERIALS AND METHODS Collection of Plant Material Aloe vera leaves were collected from the Department of Horticulture, Professor Jayashanker Agricultural University hyderabad and authenticated by pharmacognosist Dr. BabashankarRao, School of Pharmacy, Hyderabad and a voucher specimen (No: LCP/COG/4000) was deposited in department of Pharmacognosy. Preparation of Aloe vera Gel The fully expanded leaves of Aloe vera were selected from plants, washed with distilled water and were subjected to surface sterilization with 70% ethyl alcohol followed by 0.1% HgCl2. The parenchymatous covering of the leaves were peeled and the gel drained out. Slurry was formed with the help of pestle and mortar.[4] Preparation of the Extract For the preparation of ethanolic extract, fresh leaf gel was dried in the oven at 55 0 C for 48h and then powdered. Twenty grams of this powder was soaked in 200ml.of solvent namely ethanol for 24h. The contents were then filtered through what man filter paper no.1 and the filtrate was evaporated to dryness. The obtained powder is ready to use for testing. [5] Determination of LD50 of Ethanolic Extract of Aloe vera The acute toxicity of ethanolic extract of Aloe vera was identified by using albino mice of either sex (20-25g), maintained under standard husbandry conditions. The animals were fasted for 3 h prior to the experiment. Animals were administered with single dose of ethanolic extract of Aloe vera and observed for its mortality up to 48h study period (short term toxicity), based on short term toxicity profile, the next dose was determined as per OECD guidelines No. 425. From the LD50dose 1/20th, 1/10th and 1/5th doses were selected and considered as low, medium and high doses respectively and used in the entire study. [6] Glipizide Dose selection The human dose (10mg/kg, P.O) of Glipizide extrapolated to rats based on body surface area is selected. Rat dose = Human dose × 0.018

Induction of Diabetes Rats were fasted overnight before inducing diabetes with streptozotocin. The rats were given an intraperitoneal injection of streptozotocin (50 mg kg-1) freshly prepared in 0.1M sodium citrate buffer. The diabetic state was confirmed 48 h after streptozotocin injection. Threshold value of fasting blood glucose was taken as >200 mg dL-1. Diabetic rats were weighed matched for body weight and divided into following group consisting six animals each. [8]

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Experimental Animals Wistar rats weighing 200-250 gm were used in the study and given standard laboratory diet, clean drinking water was made available ad libitum. The animals were kept under standard lab conditions at 20-25◦C, 35 to 65% humidity and 12h light/dark cycle. The rats were acclimatized to the laboratory conditions week prior to the experiment. The experiment protocol was duly approved by institutional animal ethics committee.

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By using above formula the human dose of Glipizide is extended to rat as TD (0.18mg/200g, p.o). [7]

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Experimental Design Phase I: Preparation of ethanolic extract of Aloe vera gel. Phase II: Determination of LD50 and dose selection of the ethanolic extract of Aloe vera gel. Phase III: Study of herb drug interaction between ethanolic extract of Aloe vera gel and Glipizide in the streptozotocin induced diabetic rats by estimation of serum glucose levels. Experimental Procedure: Group I: Diabetic negative control Group II: Diabetic rats administered with ethanolic extract of Aloe vera gel at a dose 20mg/200g body weight. Group III: Diabetic rats administered with ethanolic extract of Aloe vera gel at a dose 40mg/200g body weight. Group IV: Diabetic rats administered with ethanolic extract of Aloe vera gel at a dose 80mg/200g body weight. Group V: Diabetic rats administered with glipizide TD (0.18mg/200g, p.o). Group VI: Diabetic rats administered with high dose (80mg/kg) of Aloe vera gel extract and glipizide TD (0.18mg/200g, p.o). Blood Glucose Estimation Blood sample was obtained through puncture tail vein and glucose levels was estimated on 0, 7, 14, 21 and 28 th day by AccuCheck Glucometer. Body Weight Determination Weight of rats was recorded at before and after the study period of 28 days. % change in body weight is calculated and graph is plotted. RESULTS The effect of oral administration of Aloe vera, glipizide and their combinations on blood glucose level showed in Fig.1. All the treatment groups showed significant (p