Enhanced hypoglycaemic effects of metformin by valsartan in a diabetic rat model

The objective of this study was to establish the effect of valsartan on the hypoglycaemic effect of metformin. Forty-four 8-week-old Sprague-Dawley rats were fed on a high fat diet or standard diet for six weeks. Diabetes mellitus was induced by administering alloxan monohydrate 120 mg/kg intraperitoneally in rats on high fat diet. Valsartan had no significant effect on blood glucose levels in non-diabetic rats. Treatment of diabetic rats with a combination of metformin and valsartan at 5mg/kg (-10.8±8.5%), 15 mg/kg (-43.0±13.7%), and 30 mg/kg (-28.6±9.1%) for 14 days resulted in significant differences in the change in blood glucose levels compared to treatment with metformin alone (+9.5±9.1%) (F=4.351; d.f.=3;16; p=0.0201). Valsartan enhanced the hypoglycaemic effects of metformin in diabetic rats after two weeks of treatment. However, valsartan did not have significant effect on glucose tolerance in both nondiabetic and diabetic rats.Keywords: hypoglycaemia, valsartan, metformin, diabete

Phosphites for the control of anthracnose in common bean.

The objective of this work was to evaluate the effect of phosphites in the protection of common bean (Phaseolus vulgaris) against anthracnose. Different phosphite formulations were evaluated by quantifying peroxidase and polyphenol oxidase activity, total phenols, and lignin content. The treatments consisted of sprayings, in the V4, R5, and R7 stages, with: the K, Zn, Mn, K+Mn, K+salicyclic acid, and Cu phosphites; salicylic acid; acibenzolar-S-methyl; and the fungicide azoxystrobin; besides a control, without sprayings. The area under the disease progress curve was lower in plants that received applications of the K and Mn phosphites, whose values ranged between 74 and 81%, compared with the control. The K, Zn, and K+salicyilic acid phosphites were effective in controlling the disease. In addition, disease severity was lower with the application of the K, Zn, and Mn phosphites than with the control. Enzyme (peroxidases and polyphenol oxidases) activity and levels of soluble phenols were higher in common bean plants treated with the K and Mn phosphites, although no change was detected in the levels of soluble lignin in the same tissue. Phosphite application reduces the severity of the disease, can enhance enzymatic activity, and is an effective alternative for the control of anthracnose in common bean

Preparation and Evaluation of Pralidoxime-Loaded PLGA Nanoparticles as Potential Carriers of the Drug across the Blood Brain Barrier

Pralidoxime is an organophosphate antidote with poor central nervous system distribution due to a high polarity. In the present study, pralidoxime-loaded poly(lactic-co-glycolic acid) nanoparticles were prepared and evaluated as a potential delivery system of the drug into the central nervous system. The nanoparticles were prepared using double emulsion solvent evaporation method. Poly(lactic-co-glycolic acid) (PLGA) in ethyl acetate made the organic phase and pralidoxime in water made the aqueous phase. The system was stabilized by polyvinyl alcohol. Different drug/polymer ratios were used (1 : 1, 1 : 2, and 1 : 4) and the fabricated particles were characterized for encapsulation efficiency using UV-VIS Spectroscopy; particle size distribution, polydispersity index, and zeta potential using photon correlation spectroscopy; and in vitro drug release profile using UV-VIS Spectroscopy. Mean particle sizes were 386.6 nm, 304.7 nm, and 322.8 nm, encapsulation efficiency was 28.58%, 51.91%, and 68.78%, and zeta potential was 5.04 mV, 3.31 mV, and 5.98 mV for particles with drug/polymer ratios 1 : 1, 1 : 2, and 1 : 4, respectively. In vitro drug release profile changed from biphasic to monobasic as the drug/polymer ratio decreased from 1 : 1 to 1 : 4. Stable pralidoxime-loaded PLGA nanoparticles were produced using double emulsion solvent evaporation techniques

INVESTIGATION OF THE TOXICOLOGICAL AND PHARMACOLOGICAL ACTIVITY OF A HYDROETHANOLIC EXTRACT OF BOOPHONE DISTICHA BULB

Boophone disticha is a highly poisonous bulb. It has been used systemically in traditional medical practice in Zimbabwe and neighbouring countries for the management of various central nervous system conditions including hysteria. Abuse of the plant by teenagers in Zimbabwe for its claimed hallucinogenic effects has also been reported, with the advent of serious toxicity in some cases. The aim of the present work was to describe the symptomatology, neurotoxicological effects and lethality of acute and subacute ingestion and of a hydro-ethanolic plant extract of the bulb of Boophone disticha in rats. Initially, we set out to estimate the LD50 of this extract using a modified Up-and-down procedure for acute toxicity determination. We then used a Functional Observational Battery (FOB) to identify the neurotoxicological effects of the extract after both acute and repeated oral intake. Additionally we studied the genotoxic potential of the Boophone extract using the Ames test. Finally we sought to investigate the putative neuropharmacological effects i.e. anxiolytic-like and antidepressant-like activity in a murine model. Findings in the acute toxicity and neurotoxicological assessment, showedan estimated oral LD50 of between 120 and 240 mg/kg. For doses of 240 mg/kg and less, signs of toxicity began approximately 10 minutes after gavage, and the most prominent initial signs were head tremors (at 50 mg/kg) and body tremors, severe body tremors(>360 mg/kg) followed by convulsions. Generally, symptoms of toxicity lasted approximately 2 hours for doses of 240 mg/kg and less; and 3 hours for doses over 240 mg/kg for animals that survived. These results point to a rapid gastrointestinal absorption of the active principles in the plant extract. The most prominent neurotoxicological effects were increased flaccid limb paralysis and spastic hind-limb paralysis. Tachypnoea was noted at low doses and higher doses produced laboured breathing. The retropulsion observed with higher doses could indicate the reported hallucinogenic effects of the plant extract. Subacute assessment showed the similar profile symptoms as with acute toxicity.The main subacute toxic effects of Boophone disticha like the acute effects seem to be mediated via interference with the neuronal pathways especially the central dopaminergic and motor neurons. Target organs, as observed by changes in organ weight appear to be liver, small and large intestines, stomach, central nervous system and peripheral nervous system. Boophone disticha extract was genotoxic from concentrations 1000μg/plate and above with both TA98 and TA100 Salmonella typhimurium species irrespective of the metabolic status of the system. The 500μg/plate concentrations of the Boophone extract were not associated with any genotoxicity and 2500μg/plate concentration is potential cytotoxic which could have masked the genotoxic effects at this concentration. P a g e | vi Boophone disticha extract showed Anxiolytic-like activity in the elevated plus maze test by significantly changing the percentage time spent in open arms, number of open arm entries, rearing, unprotected head dips and stretch attend postures. The 10m/kg dose had the most prominent effects compared to the higher dose which were comparable to the positive control. Repeated dosing enhanced the antidepressant-like activity of the Boophone extract. Therefore from the pharmacological findings of our studies, despite being very toxic Boophone disticha proved to be an important source of lead compounds for future drug development. Therefore further investigations are necessary to determine the target site and efficacy of Boophone alkaloids with in vivo models.,This work was supported by IFS grant number F/4187-

Cognitive-Enhancing Effect of a Hydroethanolic Extract of Crinum macowanii against Memory Impairment Induced by Aluminum Chloride in BALB/c Mice

Crinum macowanii is a bulbous plant indigenous to many parts of Southern Africa. Extracts of C. macowanii have gained interest since the discovery of various alkaloids, few of which possess acetylcholinesterase inhibitory activity. The present study was performed to evaluate the effect of a crude hydroethanolic extract of C. macowanii against aluminum chloride-induced memory impairment in mice using the Morris water maze and the novel object recognition task. C. macowanii (10, 20, and 40 mg/kg p.o) was administered daily for five weeks, while donepezil (3 mg/kg p.o) was used as the positive control. C. macowanii at a dosage of 40 mg/kg showed a significantly lower escape latency than the negative control (P<0.0001) and was found to be comparable to donepezil 3 mg/kg in the Morris water maze test. C. macowanii at 40 mg/kg exhibited a significantly higher discrimination index than aluminum chloride-treated mice in the novel object recognition task. The results may support the usefulness of C. macowanii in the management of dementia and related illnesses

Anxiolytic activity of a Boophone disticha: Behavioral analysis in mice subjected to early maternal separation followed by later stressors: paper presented at the International summit on past and present research systems of green chemistry;August 25-27, 2014 Hilton Philadelphia Airport, USA

Paper presented at the International summit on past and present research systems of green chemistry;August 25-27, 2014 Hilton Philadelphia Airport, USABackground: Boophone disticha is one of the commonly used bulbous plants in the treatment of anxiety disorders by indigenous people of Zimbabwe and surrounding countries but there is currently lack of scientific evidence for such claims. Therefore, the current study aimed to evaluate the anxiolytic efficacy of B. disticha aqueous ethanolic extract in adult Onincis France I(OFI) mice subjected to early life stress followed by later stressors. Methods: OFI mice were assigned to two groups at birth. Group Amice (control) were left undisturbed during stress procedures while Group B litter (MS+FS) was subjected to three hours daily maternal separation (MS) from PND2 to PND14,followed subsequently with twenty minutes of forced swim stress (FS) during adolescence (on PND35) and adulthood (on ND60 and PND90). On PND91, thirty MS+FS mice from Group B were randomly assigned to five groups (B1-B5; n=6 each) for further treatments. Group A (n=6) and Group B1 mice were given six daily oral doses from PND92-97 of normal saline (vehicle); Group B2received diazepam, 1mg/kg body weight (BW); whilst Group B3, B4and B5were given low, medium and high dose of B. disticha extract at dosages of 10, 25 and 40 mg/kg BW respectively. On PND98, the open field and elevated plus maze tests were used to obtain psychopharmacological properties of B. disticha. Results: Mice subjected to repeated early MS and subsequent FS during adulthood showed robust phenotypic abnormalities as compared to control undisturbed littermates, suggestive of increased anxiety-like behavior and inhibited exploratory locomotion. The benzodiazepine receptor agonist diazepam (1 mg/kg) produced a significant anxiolytic-like effect in the open field and elevated plus maze in stressed anxious mice. Current results found that stressed Mice treated with B. disticha aqueous extract also expressed lower scores of anxiety-like behaviors and higher exploratory and locomotor activities than the vehicle treated group. Conclusions: The present findings demonstrate that abnormal anxiety-like and exploratory behavioral phenotypes in stressed mice are sensitive to diazepam and suggest that B. disticha is also effective in ameliorating these abnormalities