Irwin Test Research Articles

Developing a heat map for CNS profiling based on the Irwin test

Developing a heat map for CNS profiling based on the Irwin test

The assessment of single-housed vs. pair-housed rats on the Irwin test

The assessment of single-housed vs. pair-housed rats on the Irwin test

Abstract 4746: Pharmacological characterization of BAY-876, a novel highly selective inhibitor of glucose transporter (GLUT)-1 in vitro and in vivo

Abstract One hallmark of cancer is the accelerated metabolism, high energy requirements, and increased glucose uptake by the tumor cells, the latter being the first and rate-limiting step for glucose metabolism. Glucose transport into the tumor cell is mediated by facilitative high-affinity glucose transporter (GLUT) proteins. Among the 14 GLUT proteins, expression of GLUT1 in normal organs is nearly exclusively restricted to the blood brain barrier, while other GLUTs are also expressed in a wide variety of vital organs such as liver and heart. Interestingly, GLUT1 expression is highly regulated by hypoxia-inducible factor (HIF)-1α, a key driver of tumor progression. In line with this finding, GLUT1 over-expression was found to be associated with tumor progression and poor overall survival in various tumor indications. Consequently, GLUT1 represents a potential target for cancer treatment. Therefore, we have developed a highly-selective GLUT1 inhibitor, namely BAY-876, with selectivity over GLUT2, 3, and 4 of 4700-, 800-, and 135-fold, respectively. We here show for the first time the pharmacological characterization of BAY-876, comprising inhibition of glucose-uptake, anti-proliferative activity in vitro, and anti-tumor efficacy in vivo in models of different tumor indications in monotherapy as well as first results on the combinability of BAY-876. Furthermore, at the therapeutic dose, BAY-876 treatment did not show any relevant finding on the behavior of treated mice in the Irwin test, assuming no or only minor effects on brain function. In conclusion, BAY-876 is the first GLUT1-selective inhibitor which reduces glucose uptake and growth of tumor cells with sufficient tolerability at the efficacious dose in preclinical models. Citation Format: Charlotte Kopitz, Luisella Toschi, Carolyn Algire, Mélanie Héroult, Anna-Lena Frisk, Kirstin Meyer, Arndt Schmitz, Eleni Lagkadinou, Heike Petrul, Iring Heisler, Roland Neuhaus, Bernd Buchmann, Herbert Himmel, Marcus Bauser, Andrea Haegebarth, Karl Ziegelbauer. Pharmacological characterization of BAY-876, a novel highly selective inhibitor of glucose transporter (GLUT)-1 in vitro and in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4746.

Assessing the predictive value of the rodent neurofunctional assessment for commonly reported adverse events in phase I clinical trials

Central Nervous System (CNS)-related safety concerns are major contributors to delays and failure during the development of new candidate drugs (CDs). CNS-related safety data on 141 small molecule CDs from five pharmaceutical companies were analyzed to identify the concordance between rodent multi-parameter neurofunctional assessments (Functional Observational Battery: FOB, or Irwin test: IT) and the five most common adverse events (AEs) in Phase I clinical trials, namely headache, nausea, dizziness, fatigue/somnolence and pain. In the context of this analysis, the FOB/IT did not predict the occurrence of these particular AEs in man. For AEs such as headache, nausea, dizziness and pain the results are perhaps unsurprising, as the FOB/IT were not originally designed to predict these AEs. More unexpected was that the FOB/IT are not adequate for predicting ‘somnolence/fatigue’ nonclinically. In drug development, these five most prevalent AEs are rarely responsible for delaying or stopping further progression of CDs. More serious AEs that might stop CD development occurred at too low an incidence rate in our clinical dataset to enable translational analysis.

Tamizaje fitoquímico y evaluación de la actividad sobre el sistema nervioso central del extracto etanólico de Eugenia clarensis Britton & P.Wilson

Context: Eugenia clarensis Britton & P. Wilson is an endangered plant endemic of central region of Cuba. Aims: To perform phytochemical profile of ethanolic leaf extract of E. clarensis and evaluate its central nervous system (CNS) activity. Methods: The dried powder of leaves of E. clarensis was exhaustively extracted with ethanol by maceration. This extract underwent preliminary phytochemical analysis and these results were corroborated by the thin layer chromatographic technique. CNS effects were investigated in NMRI mice at doses 200, 400 and 800 mg/kg using Irwin test, curiosity tests and traction. Results: Phytochemical screening suggested the presence of phenols, tannins, triterpenoids, sterols, flavonoids, coumarins, quinones, resins and reducing sugar. The oral administration of this extract, in Irwin test, produced slight reduction in spontaneous motor activity and muscle tone in mice at doses of 400 and 800 mg/kg, moreover, it exhibited diuretic activity. In addiction this extract at dose 800 mg/kg decreased number of times which mice introduced its head into holes in comparison with the negative control. In the traction test, the mice treated with the extract showed a non-significant failure in traction at all doses tested. Conclusions: These findings indicate that the extract in higher doses has exerts a weak sedative and non-effect about the motor coordination. The results obtained in the preliminary phytochemical testing thus suggest that the ethanolic leaf extract of E. clarensis contains some metabolites, which may be responsible of sedative action.

Effect of λ-Cyhalothrin on Redox Homeostasis and Neuropharmacological Activities in Wistar Rats

The present study was carried out to assess the behavioral, neurobiochemical changes following λ-cyhalothrin exposure and to evaluate the neuropharmacological activity in in Wistar rats using well defined animal models. Neurobehavioral assessment was carried as per modified Irwin test. To determine the oxidative profile of brain tissue, rats were randomly divided into two groups consisting of six rats each. Group I served as vehicle-treated control and Group II received λ-cyhalothrin at 7.8 mg/kg (per os) for a period of 7 days. The neuropharmacological studies were carried out in rats following administration of λ-cyhalothrin at a dose rate (per os) of either 1/5th or 1/10th LD50. Neurobehavioral assessment showed prominent autonomic sign(s) followed by depression following single administration of λ-cyhalothrin (1/10th LD50). Short-term exposure to λ-cyhalothrin-induced lipid peroxidation as evident by significant increase in malondialdehyde levels in the brain tissue. Marked alteration of antioxidant defense mechanism(s) in the brain tissue was observed by the reduced activity of superoxide dismutase and catalase. Further, the tissue glutathione (GSH) (reduced; GSH) content was also significantly (P < 0.05) depleted. λ-cyhalothrin exerted a significant reduction in spontaneous motor activity as well as forced motor activity in dose-dependent manner, thus demonstrated reduced activity of central nervous system. Interestingly, λ-cyhalothrin exerted nociceptive action, which was comparable to control group. Further, there was marked increase in the duration of strychnineinduced (2 mg/kg; i.p.) tonic-clonic convulsions in rats. Overall, short-term exposure to sub lethal dose of λ-cyhalothrin causes disturbances in brain redox homeostasis and alters neuropharmacological activity in Wistar rats.

Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors

This study assessed the anticonvulsant and seizure generation effects of carbamazepine (CBZ), oxcarbazepine (OXC) and eslicarbazepine (S-Lic) in wild-type mice. Electrophysiological recordings were made to discriminate potential cellular and synaptic mechanisms underlying anti- and pro-epileptic actions. The anticonvulsant and pro-convulsant effects were evaluated in the MES, the 6-Hz and the Irwin tests. Whole-cell patch-clamp recordings were used to investigate the effects on fast excitatory and inhibitory synaptic transmission in hippocampal area CA1. The safety window for CBZ, OXC and eslicarbazepine (ED50 value against the MES test and the dose that produces grade 5 convulsions in all mice), was 6.3, 6.0 and 12.5, respectively. At high concentrations the three drugs reduced synaptic transmission. CBZ and OXC enhanced excitatory postsynaptic currents (EPSCs) at low, therapeutically-relevant concentrations. These effects were associated with no change in inhibitory postsynaptic currents (IPSCs) resulting in altered balance between excitation and inhibition. S-Lic had no effect on EPSC or IPSC amplitudes over the same concentration range. The CBZ mediated enhancement of EPSCs was blocked by DPCPX, a selective antagonist, and occluded by CCPA, a selective agonist of the adenosine A1 receptor. Furthermore, reduction of endogenous adenosine by application of the enzyme adenosine deaminase also abolished the CBZ- and OXC-induced increase of EPSCs, indicating that the two drugs act as antagonists at native adenosine receptors. In conclusion, CBZ and OXC possess pro-epileptic actions at clinically-relevant concentrations through the enhancement of excitatory synaptic transmission. S-Lic by comparison has no such effect on synaptic transmission, explaining its lack of seizure exacerbation.

Effects of hyrdroethanolic leaf extract of Pseudospondias microcarpa (A. Rich.) Engl. (Anacardiaceae) on the central nervous system in mice

Pseudospondias microcarpa (Anacardiaceae), the African grape tree, is used for various CNS disorders. The neuropharmacological activities of the hydroethanolic leaf extract of Pseudospondias microcarpa (PME) were screened in mice. In this study, the central nervous system (CNS) activity was tested in various animal models including Irwin test, pentobarbitone-induced sleeping time, spontaneous motor activity, rotarod test, pentylenetetrazole-induced convulsions and tail immersion test. The extract produced sedation and analgesia in the Irwin test with an LD50 above 3000 mg kg-1 . PME potentiated pentobarbitone sleeping time and induced hepatic enzymes. It however, showed no effect on locomotor activity or motor coordination. Furthermore, the extract blocked convulsions induced by PTZ and showed analgesic activity in the tail withdrawal test. The present investigation suggests that PME may act as a sedative with analgesic and anticonvulsant activity, and thus supporting its use as a sedative and for the relief of various nervous system disorders.

Evaluation of pro-convulsant risk in the rat: spontaneous and provoked convulsions.

The aim of the present study was to evaluate the utility of different tests performed in the absence or presence of factors promoting seizures in order to evaluate the pro-convulsant effects of drugs. We studied the effects of theophylline in the rat since this is a well-known pro-convulsant substance in humans. The occurrence of spontaneous convulsions following administration of theophylline was evaluated by observation in the Irwin Test and by measuring brain activity using video-EEG recording in conscious telemetered animals. Theophylline was also tested in the electroconvulsive shock (ECS) threshold and pentylenetetrazole (PTZ)-induced convulsions tests, two commonly used models of provoked convulsions. In the Irwin test, theophylline induced convulsions in 1 out of 6 rats at 128 mg/kg. Paroxysmal/seizure activity was also observed by video-EEG recording in 4 out of the 12 animals tested at 128 mg/kg, in presence of clonic convulsions in 3 out of the 4 rats. Paroxysmal activity was observed in two rats in the absence of clear behavioral symptoms, indicating that some precursor signs can be detected using video-EEG. Clear pro-convulsant activity was shown over the dose-range 32-128 mg/kg in the ECS threshold and PTZ-induced convulsions tests. Evaluation of spontaneous convulsions provides information on the therapeutic window of a drug and the translational value of the approach is increased by the use of video-EEG. Tests based on provoked convulsions further complement the evaluation since they try to mimic high risk situations. Measurement of both spontaneous and provoked convulsions improves the evaluation of the pro-convulsant risk of novel pharmacological substances.

Repeated measurements of motor activity in rats in long-term toxicity studies

IntroductionIn the light of 3R (replace, reduce, refine) principles in animal experimentation and increased focus on delayed effects of treatment on central nervous system, the incorporation of behavioural tests into standard toxicology studies as a complement or substitution of a stand-alone safety pharmacology study appears very attractive, but poses some challenges. In the present study, we evaluated the results of an open field test (standard part of the behavioural test batte- ries) incorporated into the 3-month regulatory toxicology study. MethodsThe study was performed in two rat strains most commonly used in toxicology studies (Wistar and Sprague Dawley (SprD)). Open field test was performed according to the standard protocol for stand-alone behavioural test (modified Irwin test) before the start of treat- ment (Day-7, “naïve” animals), on Day 2, inWeek 6 and inWeek 13 of treatment with saline. Results and DiscussionThere was no overall difference between strains, and onlyminor differenceswere detected at the individual time points. With regard to time effect, the average values for most of the parameters were comparable throughout the study but individual variability in the performance in the arena was increased at repeated measurements compared to the start. In conclusion, performance in the open field arena did not differ principally betweenWistar and SprD rats of both genders. However, individual variability in the behaviour in the open field arena increased with time. This has clear implications for deciding the appropriate group size for this type of study and has to be taken into account in the design of a toxicology study with integrated safety pharmacology endpoints.

Advantageous safety profile of a dual selective alpha2Cagonist/alpha2Aantagonist antinociceptive agent

A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist agent vs. the nonselective agonist clonidine.

Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity

A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.

The RotaRod test for motor coordination: Methodological considerations and potential added value vs. the Irwin test

The RotaRod test for motor coordination: Methodological considerations and potential added value vs. the Irwin test

Abstract 5687: Development of glutathione pegylated liposomal doxorubicin (2B3-101) for the treatment of brain cancer

Abstract Treatment options for brain cancer are limited and overall prognoses are poor. Glutathione pegylated liposomal doxorubicin (2B3-101) is being developed as a new treatment option for patients with brain cancer. It is essentially based on the already marketed pegylated liposomal doxorubicin (Doxil), with an additional glutathione (GSH) coating to safely enhance delivery across the blood-brain barrier. In a GLP safety study 2B3-101 was administered by intravenous bolus injection on days 1, 15 and 29 to Wistar rats at 1.75, 3.5 and 7 mg/kg. Doxil (7 mg/kg), empty GSH-PEG-liposomes, and vehicle were included, resulting in 6 groups (10 animals/sex/group). Additional animals were allowed 4 weeks of recovery or were used for toxicokinetic analysis. From observations during the in-life part of the study, as well as after histopathological investigations, no major differences were noted between 2B3-101 and Doxil at 7 mg/kg q14dx3. No treatment-related changes in the brain were observed neither after repeated 2B3-101 exposure, nor after treatment with empty GSH-PEG liposomes. In addition, 2B3-101 did not result in doxorubicin-related toxicity in heart tissue. After 1st and 3rd administration of 7 mg/kg, plasma AUC values were 10-44% higher for Doxil when compared to 2B3-101, while C0 values were considered similar for both drug substances. Apparent half-lives for Doxil were 36.1 and 32.6 hours in males and females after the 3rd administration, respectively. For 2B3-101 these values were slightly shorter at 30.0 and 28.8 hours in males and females, respectively. The doxorubicin brain/plasma ratio showed retention of both 2B3-101 and Doxil after repeated doses, where 2B3-101 resulted in significantly higher doxorubicin retention in the brain 2 weeks after the 3rd administration (p<0.02). A modified Irwin test in male Wistar rats (n=8 per group) showed no neurobehavioral effects and no effects of 2B3-101 on body temperature after administration of 1.75 mg/kg, 3.5 mg/kg and 7 mg/kg. Also, empty GSH-PEG liposomes and Doxil did not result in neurobehavioral effects and effects on body temperature. Efficacy of GMP grade 2B3-101 at the maximum tolerated dose was confirmed in mice with intracranial U87 xenografts; compared to saline 10 mg/kg q4dx4 and 18 mg/kg q8dx2 showed a survival benefit of up to 60%, where 18 mg/kg q8dx2 seemed superior. In addition, in mice carrying subcutaneous MDA-MB-231 xenografts it was shown that 10 mg/kg q4dx3 2B3-101 and Doxil both produced significant anti-tumor activity, were well tolerated, and gave similar weight loss profiles. In conclusion, the therapeutic benefit and predictable safety profile of clinical-scale 2B3-101 was successfully demonstrated in preclinical studies. A clinical trial to determine the safety, tolerability and pharmacokinetics of 2B3-101 in patients with solid tumors and brain metastases or recurrent malignant glioma was initiated in June 2011. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5687. doi:1538-7445.AM2012-5687

NEUROPHARMACOLOGICAL ASSESSMENT OF AN AQUEOUS BARK EXTRACT OF <i>ANTIARIS TOXICARIA</i> (PERS.) LESCH. (MORACEAE) IN RODENTS

Antiaris toxicaria is a plant traditionally used in Ghana for the treatment of various neurological conditions such as epilepsy and pain. This present study therefore seeks to screen for the neuropharmacological activities of the aqueous extract of Antiaris toxicaria (AAE) stem bark. The effect of Antiaris extract on pentobarbital-induced sleeping time, tail immersion test, spontaneous locomotor activity, motor coordination, PTZ-induced convulsions as well as the Irwin test was investigated. The extract produced analgesia and Straub tail at (300-3000 mg kg-1) in the Irwin test suggestive of a morphine-like action. These effects were absent after 24 h. No deaths were recorded in the test estimating the LD50 to be above 3000 mg kg-1. Spontaneous locomotor activity of the mice in the activity meter test was decreased significantly (p

Neuro-pharmacological effects of Crinum zeylanicum in mice.

The aim of present study was to evaluate some effects of Crinum zeylanicum (C. zeylanicum) on central nervous system. C. zeylanicum methanolic bulb extract (250-1000 mg/kg orally), 2 mg chlorpromazine and 4 mg diazepam /kg body weight intraperitoneally respectively were tested in mice using Irwin test, pentobarbitone-induced sleep test, spontaneous motor activity, apomorphine-induced stereotype behaviour, and rota-rod performance. The C. zeylanicum bulb extract significantly and dose-dependently decreased apomorphine-induced hyperactivity in mice (p<0.001). The Irwin test revealed dose-dependent central depressant effect of the extract, shortened (p<0.05-0.01) the onset of sleep and prolonged the duration of sleep. The extract produced significant (p<0.05-0.001) and dose- dependent reduction in spontaneous motor activity and apomorphine-induced stereotype behaviours in mice. The extract had no effect on performance of mice on rotarod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.

General Pharmacology Studies on ß-Domain Deleted Recombinant Factor VIII

beta-Domain deleted recombinant factor VIII (GC-rAHF), newly developed by Korea Green Cross Co., is a novel therapeutic for hemophiliacs and is currently under clinical evaluation. The general pharmacological properties of this drug were evaluated using mice, rats, guinea pigs and rabbits. Intravenous doses of 5 to 500 IU/kg were assayed in several tests to analyze their effects in vivo on various systems. The effect of the substance under study was also tested in vitro on isolated guinea pig ileum preparations at final concentrations of 5 to 50 IU/kg. The result of this study showed that GC-rAHF did not affect general behavior in the Irwin test. Similarly the drug was not found to affect neither normal body temperature nor the spontaneous activity in mice. In addition, it was not found to induce pharmacologically significant alterations of the cardiovascular and respiratory parameters in rats. No effects were observed either in the pentobarbital sodium-induced sleep-induction time and duration, in writhing test or in the test of pentetrazole-induced convulsion. Finally, the tested drug did not modify the gastrointestinal motility, acetylcholine or histamine-induced contraction of the isolated guinea pig ileum, nor gastric secretion. The results demonstrated that GC-rAHF has no effects on the central nervous, cardiovascular, respiratory and digestive systems in the doses of 5, 50 and 500 IU/kg in vivo and 5, 10, 50 and 100 IU/kg in vitro.

Comparison of methods for the assessment of locomotor activity in rodent safety pharmacology studies

IntroductionGeneral neurobehavioral assays, like a modified Irwin test or a functional observational battery, are necessary for central nervous system (CNS) safety pharmacology testing near the end of the target validation (early discovery) stage of preclinical drug development. However, at earlier stages, when a greater number of test compounds must be screened for potential CNS side effects, locomotor activity assessment may be a better tool for the comparison of compounds. MethodsSpontaneous locomotor activity counts obtained from two automated test systems – an infrared beam-based activity meter (Actimeter) and the mechanical vibration-based LABORAS – were compared in rats dosed with chlorpromazine (2–8mg/kg) or caffeine (3–24mg/kg), p.o. A modified Irwin test was also performed to visually observe the neurobehavioral effects. ResultsIn all three assays, dose-dependent sedation- and excitation-related effects were observed with chlorpromazine and caffeine, respectively. The two automated activity-detection systems exhibited similar sensitivities in determining changes in locomotor activity, but with the LABORAS being more sensitive than the Actimeter in detecting caffeine-induced increases in vertical activity (rearing behavior). DiscussionInfrared beam-based activity detection systems and LABORAS provide relatively-comparable quantitative data regarding locomotor activity. Practical considerations, such as relative cost versus degree of versatility, should be considered when deciding which system to use for the screening of test compounds during the earliest stages of preclinical drug development.

Executive Functions of Postweaning Protein Malnutrition in Mice

It is well known that nutritional status during the fetal and/or lactation period is important for the development of the central nervous system (CNS). In contrast, the effect of malnutrition on postweaning development has not yet been thoroughly investigated. In the present study, we analyzed the behavioral and neuroanatomical effects of protein malnutrition (PM) postweaning in mice. Starting at 20-21 d of age, male ddY mice were maintained on a 5% casein diet (PM group) or 20% casein diet (control group) for 20 d. On the 20th d, body and brain weights of PM mice were lower than those of the control group. PM mice exhibited excessive alertness and spontaneous activity under novel conditions in the Irwin test. In addition, PM mice showed increased open arm exploration in the elevated plus maze compared to control mice. These results suggest that hyperactivity and reduced anxiety behavior or higher impulsiveness in PM mice could be due to an immature brain.

Antidiabetic effect of Symplocos cochinchinensis (Lour.) S. Moore. in type 2 diabetic rats

Symplocos cochinchinensis (Lour.) S. Moore. is used in Indian system of traditional medicine to treat diabetes mellitus. The present study aims to investigate the antidiabetic efficacy of the hexane extract of Symplocos cochinchinensis leaves in high fat diet-low streptozotocin (STZ) induced type 2 diabetic rats. The doses for the study were fixed based on Irwin test. The hypoglycemic effect of the hexane extract of Symplocos cochinchinensis leaves were studied in normal rats. Oral glucose and insulin tolerance tests were carried out. The antihyperglycemic effect of the hexane extract at 250 and 500 mg/kg was studied in high fat diet-low STZ induced type 2 diabetic rats for 28 days. The extracts showed no adverse effects up to 5 g/kg concentration. In hypoglycemic study, after treatment with hexane extract at 250 and 500 mg/kg the blood glucose was mildly reduced. In oral glucose tolerance test, the treatment with the hexane extract at 250 and 500 mg/kg showed a highly significant reduction of 12.07% and 23.58% in plasma glucose levels, respectively 30 min after glucose load. The insulin tolerance test also showed improved insulin sensitivity after 60 min of insulin treatment. In high fat diet-low STZ induced type 2 diabetic rats, after 28 days treatment with the hexane extract at 250 and 500 mg/kg reduced the plasma glucose level by 17.04% and 42.10%, respectively. A significant reduction in plasma insulin, plasma and hepatic total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) and a significant increase in liver glycogen were observed in treated diabetic rats. This study demonstrated the potential antidiabetic property of hexane extract of Symplocos cochinchinensis leaves on type 2 diabetes mellitus, thus justifying its traditional usage.