Preclinical Study to Evaluate the Effect of Polyherbal Formulation on Metformin: Potential Herb-drug Interaction

2019 ◽  
Vol 9 (1) ◽  
pp. 69-76
Author(s):  
Devendra Kumar ◽  
Neerja Trivedi ◽  
Rakesh Kumar Dixit
Keyword(s):  
Diabetes Mellitus ◽  
Preclinical Study ◽  
Oral Route ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Polyherbal Formulation ◽  
Sprague Dawley Rats ◽  
Significant Difference

Objective: The aim of the present study was to examine the effect of a polyherbal formulation (PHF) on pharmacokinetics and pharmacodynamics of metformin in rats. Methods: The present study was conducted to determine the beneficial outcomes of PHF along with metformin by studying herb-drug interactions. PHF was prepared by five indigenous herbs, Those are being used traditionally as antidiabetic in India. PHF doses (100 mg/kg/day) were administered to Sprague-Dawley rats by an oral route of different groups for multiple weeks except for control. Metformin (100 mg/kg) was orally administered at 7th and 30th day to control and PHF pretreated rats for pharmacokinetics study while pharmacodynamics study was conducted in PHF treated and untreated diabetic rats. No more significant difference was found in the pharmacokinetic parameters in PHF treated at 7th day while a significant increase was found in AUC at the 30th day. Results: The hypoglycemic effect was observed with a combination of metformin and PHF, significantly more compared to control. Metformin decreased the blood glucose 1.51 fold at 7th day and 1.7 fold at 30th day respectively, compared to control. Conclusion: Thus, this finding indicates that PHF increased the AUC of metformin. It might increase bioavailability through drug-herb interaction thereby affecting the therapeutic effect. This formulation can be considered as an adjunct to metformin in the management of diabetes mellitus.

scholarly journals Pharmacokinetics Interaction between Imatinib and Genistein in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Li Wang ◽  
Meng-ming Xia ◽  
Wei Sun ◽  
Cheng-ke Huang ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Group Control Group

The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P<0.05) decreased theAUC0-tandCmaxof imatinib.AUC0-tand theCmaxof N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect.

scholarly journals Pre-Clinical Pharmacokinetic and Pharmacodynamic Characterization of Selected Chiral Flavonoids: Pinocembrin and Pinostrobin

2015 ◽  
Vol 18 (4) ◽  
pp. 368 ◽  
Author(s):  
Casey L. Sayre ◽  
Samaa Alrushaid ◽  
Stephanie E. Martinez ◽  
Hope D. Anderson ◽  
Neal M. Davies
Keyword(s):  
Chemical Structure ◽  
In Vitro Assays ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Sprague Dawley Rats ◽  
Stereoselective Pharmacokinetics ◽  
First Time

Purpose: Delineate the stereospecific pharmacokinetics and pharmacodynamics of the chiral flavonoids pinocembrin and pinostrobin. Objective: Characterize for the first time the stereoselective pharmacokinetics of two flavonoids, pinocembrin and pinostrobin and their bioactivity in several in vitro assays with relevant roles in heart disease, colon cancer, and diabetes etiology and pathophysiology. Methods: Chiral flavonoids were intravenously and orally administered to male Sprague-Dawley rats. Concentrations in serum and urine were characterized via stereospecific HPLC or LC/MS. Pure enantiomeric forms of each flavonoid were tested, where possible, to identify the stereospecific contribution to bioactivity in comparision to their racemates. Results:  Short half-lives (0.2-6 h) in serum were observed, while a better estimation of half-life (3-26 h) and other pharmacokinetic parameters were observed using urinary data. The flavonoids are predominantly excreted via non-renal routes (fe values of 0.3-4.6 %), and undergo rapid and extensive phase II metabolism. Chiral differences in the chemical structure of these compounds result in significant pharmacodynamic differences. Conclusion: The importance of understanding the stereospecific pharmacokinetics and pharmacodynamics of two chiral flavonoids were delineated.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effect of Kalanchoe crenata Extract on Renal and Liver Impairment, Dyslipedemia and Glycemia in Streptozotocin Induced Diabetic Rats

2021 ◽  
pp. 109-125
Author(s):  
Emmanuel Effah-Yeboah ◽  
Emmanuel Dartey ◽  
Emmanuel Agyapong Asare ◽  
Janice Dwomoh Abraham ◽  
James K. Kagya-Agyemang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ethanolic Extract ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Tissue Sections ◽  
Regenerative Effect ◽  
Sprague Dawley Rats ◽  
The Family ◽  
Diabetes Melitus

Introduction: Diabetes mellitus or diabetes is a metabolic ailment which occurs as a result of insulin insufficiency or defect in insulin function, or both that leads to ihyperglycemia. Diabetes mellitus is a worldwide disease even though its prevalence in other countries vary. Kalanchoe crenata belongs to the family crassulaceae. It is also known locally as miracle plant and often utilized in Africa for medicinal purposes. The study was designed to ascertain the antidiabetic and dyslipidemic activity and effects of the ethanolic extract of both leaves and stem of Kalanchoe crenata on istreptozotocin incite diabetic rats for three (3) weeks. Methodology: 6-8 weeks old Sprague dawley rats received multiple injection of streptozotocin intraperitoneally (40mg/kg body weight) to induce diabetes melitus. Diabetes mellitus was observed and confirmed after six days of induction. The rats were given ethanolic extract of Kalanchoe crenata remarkably (10, 30 and 100mg/kg) and 5mg/kg glibenclamide orally twice daily for three weeks. Blood glucose, lipids, creatinine, urea, were then determined. Results: After week three of treatment 5mg/kg glibenclamide, 30 and 100mg/kg ethanolic extract of Kalanchoe crenata remarkably (p<0.05) decrease glycemia and improved lipidemia by decreasing overall cholesterol, LDL-C and increasing HDL-C likened to the control diabetic group. Also results from treated rats remarkably decrease blood urea nitrogen and creatinine. However, the affirmative control and the sampled treated groups showed curative and regenerative effect in the cells responsible for producing endocrine insulin “beta cells of the islets of Langerhans” located in the pancreas. Kidney and liver tissue sections of treatment groups showed a reversal of diseased insults made by the streptozotocin. Conclusion: The outcome of the research indicate that given ethanolic extract of Kalanchoe crenata remarkably contains the necessary phytochemicals for the development of a standard and effective herbal medicine for Diabetes mellitus and related complications and also with no toxic effects on the tissues of the liver, pancreas and kidney.

Gender and Contractile Functions of Slow and Fast Skeletal Muscles in Streptozotocin Induced Diabetic Sprague Dawley Rats

2012 ◽  
Vol 19 (4) ◽  
pp. 417-424 ◽  
Author(s):  
Kamil Asghar Imam ◽  
Madiha Sarwar ◽  
Usman Wali ◽  
Lubna Siddique ◽  
Shahida Perveen
Keyword(s):  
Skeletal Muscles ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Group I ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Contractile Parameters ◽  
Data Acquisition Unit ◽  
Diabetes Induction

AbstractObjectives: Diabetes mellitus has been linked with specific morphological andmetabolic abnormalities of skeletal muscle in a fiber specific manner. Aim: Thepresent study was designed to compare the contractile functions of slow and fastskeletal muscles in streptozotocin (STZ) induced diabetic male and female SpragueDawley rats. Material and methods: Thirty healthy Sprague Dawley rats (15 maleand 15 female) were divided into two groups and studied after four weeks followingdiabetes induction. The rats in group I (male diabetic; n = 15) and group II (femalediabetic; n = 15) were fed on normal pellet diet and water ad libitum and rendereddiabetic by single intraperitoneal injection of STZ 65 mg/kg body weight at the startof study (day 1). At the end of four weeks, the contractile parameters of slow soleusand fast extensor digitorum longus (EDL) muscles were recorded by iWorx advancedanimal/human physiology data acquisition unit (AHK/214). Results: At the end offour weeks, the weight of isolated soleus and EDL muscles in the male diabetic ratswas significantly higher (p < 0.001) as compared to the female diabetic rats.However, no significant difference was found in any of the contractile functions ofisolated soleus and EDL muscles when compared between the male and femalediabetic rats. Conclusion: No gender differences exist in the contractile functions ofslow and fast skeletal muscles in streptozotocin induced diabetic Sprague Dawleyrats.

scholarly journals DARAPLADIB INHIBIT ADHESION MOLECULE EXPRESSION IN AORTA AT EARLY STAGES OF ATHEROSCLEROSIS USING SPRAGUE-DAWLEY TYPE 2 DIABETES MELLITUS MODEL

2017 ◽  
Vol 10 (6) ◽  
pp. 373 ◽  
Author(s):  
Heriansyah T ◽  
Hanifa H ◽  
Andarini S ◽  
Wihastuti Titin Andri
Keyword(s):  
Diabetes Mellitus ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Fasting Blood Glucose ◽  
Sprague Dawley ◽  
Nonesterified Fatty Acids ◽  
Early Stages ◽  
Significant Difference ◽  
Atherosclerosis Treatment

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA2 specific inhibitor. It is also considered to be an atherosclerosis treatment. The aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley Type 2 DM (T2DM) model.Methods: About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p<0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p<0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group.Conclusion: Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague- Dawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.

scholarly journals The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1332
Author(s):  
Gilda M. Iova ◽  
Horia Calniceanu ◽  
Adelina Popa ◽  
Camelia A. Szuhanek ◽  
Olivia Marcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Gingival Tissue ◽  
Control Group ◽  
Albino Rats ◽  
Oxidative Stress Biomarkers ◽  
Significant Difference ◽  
The Impact ◽  
Experimentally Induced

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.

scholarly journals THE EFFECTS OF LEVELS OF ISOLATION, OR VARIETAL DIFFERENCES IN, HIGH FIBRE HULL FRACTION OF LOW GLUCOSINOLATE RAPESEED MEALS ON RAT OR PIG PERFORMANCE

1978 ◽  
Vol 58 (4) ◽  
pp. 743-752 ◽  
Author(s):  
J. J. KENNELLY ◽  
F. X. AHERNE ◽  
A. J. LEWIS
Keyword(s):  
Feed Intake ◽  
Average Daily Gain ◽  
Rapeseed Meal ◽  
Sprague Dawley ◽  
Crude Fibre ◽  
Gain Ratio ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Pig Performance ◽  
Daily Gain

Forty-eight crossbred pigs of average initial weight 21 kg were fed 10% Tower rapeseed meal (RSM) and 10% Candle RSM as partial replacements for soybean meal (SBM). Diets were formulated to be isocaloric. Pigs fed the SBM diet consumed less feed, gained significantly (P < 0.01) faster and were more efficient at converting feed to gain than those fed the RSM diets. Performance of pigs fed Candle RSM was not significantly different to that obtained with Tower RSM. In a second experiment, dehulled Tower RSM and Tower RSM hulls were mixed in amounts to produce RSM with crude fibre levels of 6.8, 10.8, 13.5 and 15.8%. The simulated RSM and Tower and Candle RSM were used to completely replace SBM in the diets of weanling (75 g) Sprague-Dawley rats. Rats fed SBM had significantly (P < 0.05) higher average daily gain (ADG) than those fed Tower or Candle RSM, or diets containing the rapeseed meats. There was no significant (P < 0.05) difference in ADG, feed intake or feed to gain ratio of rats fed either Tower or Candle RSM. Feed intake, feed to gain ratio and fecal volatile fatty acid concentrations increased while average daily gain decreased with increasing level of hulls in simulated RSM diets. There was no significant difference (P < 0.05) in thyroid weight between rats fed SBM, Tower RSM or Candle RSM.

Electroacupuncture at Zusanli Rescues the Enteric Neuronal Loss in the Stomach of Diabetic Rats

2012 ◽  
Vol 18 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
Neuronal Loss ◽  
Diabetic Rats ◽  
Enteric Neurons ◽  
Control Group ◽  
Sprague Dawley ◽  
Long Duration ◽  
Sprague Dawley Rats ◽  
Zusanli Acupoint

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.

KELULUT HONEY SUPPLEMENTATION PREVENTS SPERM AND TESTICULAR OXIDATIVE DAMAGE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

2017 ◽  
Vol 79 (3) ◽  
Author(s):  
Siti Balkis Budin ◽  
Fatin Farhana Jubaidi ◽  
Siti Nur Farahana Mohd Noor Azam ◽  
Nur Liyana Mohamed Yusof ◽  
Izatus Shima Taib ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Sperm Quality ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Control Groups ◽  
Sod Activity ◽  
Male Adult ◽  
Pathological Conditions ◽  
Sprague Dawley Rats

Previous studies found that Kelulut Honey produced by Trigona spp. bees is able to prevent oxidative damage in various pathological conditions.  Thus, the present study aimed to determine whether Kelulut Honey could prevent the sperm and testicular damage in streptozotocin-induced diabetic rats. Male Adult male Sprague-Dawley rats were divided into four groups: Non-Diabetic (NDM), Non-Diabetic with Kelulut Honey supplementation (NDMKH), Diabetic without supplementation (DM) and Diabetic with Kelulut Honey supplementation (DMKH).  Kelulut honey was given at the dose of 2.0 g/kg weight daily via gavage for 28 consecutive days. Results showed that sperm quality produced by diabetic rats supplemented with Kelulut honey significantly improved compared to the diabetic control groups (p<0.05). SOD activity and GSH level increased significantly (p<0.05) whereas PC and MDA levels significantly decreased in sperm and testis of DMKH rats when compared to DM rats (p<0.05). Histological observation showed obvious increase in spermatozoa in the lumen of epididymis and increased spermatogenic cells density in the testis of DMKH group.  In conclusion, Kelulut Honey has a potential in preventing the damage of sperm and testis in diabetic rats.

scholarly journals Oral administration of Lactobacillus casei Shirota can ameliorate the adverse effect of an acute aflatoxin exposure in Sprague Dawley rats

2018 ◽  
Vol 88 (3-4) ◽  
pp. 199-208
Author(s):  
Elham Nikbakht ◽  
Rosita Jamaluddin ◽  
S. Mohd Redzwan ◽  
Saman Khalesi
Keyword(s):  
Adverse Effect ◽  
Lactobacillus Casei ◽  
Health Effect ◽  
Acute Exposure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Lactobacillus Casei Shirota ◽  
Probiotic Treatment ◽  
Significant Difference ◽  
Aflatoxin B

Abstract. Aflatoxin B1 (AFB1) is a toxic compound commonly found in some crops with an adverse health effect on human and animals. Some beneficial microorganisms (or probiotics) such as lactic acid bacteria have shown the ability to reduce the bioavailability of aflatoxins and its intestinal absorption. However, the dose and duration of aflatoxins exposure and probiotic treatment can influence the ability of probiotics to remove aflatoxins. Therefore, this research aimed to investigate the efficacy of oral probiotic Lactobacillus casei Shirota strain (LcS) induction in an acute exposure to AFB1 in rats. Experimentally, Sprague Dawley rats were divided into three groups: AFB1 only (n = 9); AFB1 treated with LcS (n = 9); and control (no AFB1 exposure) (n = 6) groups. The blood AFB1 level of rats treated with LcS was slightly lower than the untreated AFB1 induced rats (11.12 ± 0.71 vs 10.93 ± 0.69 ng g–1). Also, LcS treatment slightly moderated the liver and kidney biomarkers in AFB1 induced rats. However, a trend for a significant difference was only observed in ALT of AFB1 induced rats treated with LcS compared to their counterparts (126.11 ± 36.90 vs 157.36 ± 15.46, p = 0.06). Rats’ body weight decreased in all animals force-fed with AFB1 with no significant difference between LcS treatment compared to the counterpart. In conclusion, this experiment indicated that probiotic LsC was able to slightly ameliorate the adverse effect of an acute exposure to AFB1 in rats. However, future studies with longer probiotics treatment or higher probiotics dose is required to confirm these findings.

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