Metformin, routinely used as first-line drug in the treatment of type 2 diabetes, has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways, which prevent the mPTP from opening and rupturing it and therefore, protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed. Given as a preconditioning and/or postconditioning agent, metformin has been shown to decrease infarct size and improve survival rates after myocardial infarction. Metformin has further been reported to restore depleted PGC-1α levels and improve mitochondrial biogenesis by increasing phosphorylation of eNOSser1177, which produces NO and leads to reduced vascular inflammation and myocardial injury after ischemia. There is strong evidence suggesting that metformin improves cardiovascular outcomes by influencing metabolic signal transduction pathways. There are growing calls for metformin use to be expanded off-label beyond the traditional glycemic control. We review experimental evidence for metformin's impact on cardiovascular disease and its underlying molecular mechanisms of action and also discuss why significant gains made in experimental conditions have not translated into significant therapeutic applications.

Introduction: Appropriately managing mental disorders is a growing priority across countries in view of the impact on morbidity and mortality. This includes patients with bipolar disorders (BD). Management of BD is a concern as this is a complex disease with often misdiagnosis, which is a major issue in lower and middleincome countries (LMICs) with typically a limited number of trained personnel and resources. This needs to be addressed. Areas covered: Medicines are the cornerstone of managing patients with Bipolar II across countries including LMICs. The choice of medicines, especially antipsychotics, is important in LMICs with high rates of diabetes and HIV. However, care is currently compromised in LMICs by issues such as the stigma, cultural beliefs, a limited number of trained professionals and high patient co-payments. Expert opinion: Encouragingly, some LMICs have introduced guidelines for patients with BD; however, this is very variable. Strategies for the future include addressing the lack of national guidelines for patients with BD, improving resources for mental disorders including personnel, improving medicine availability and patients' rights, and monitoring prescribing against agreed guidelines. A number of strategies have been identified to improve the treatment of patients with Bipolar II in LMICs, and will be followed up.

Objective: Livolin forte ® (LIV) is a hepatoprotective drug that is being used in hospitals worldwide in the treatment and management of liver diseases. However, as it appear through the available published literature, the physiological effects of the drug on the liver using a rat model of hepatotoxicity is not yet well established. This study assessed the curative and prophylactic effects of LIV on carbon tetrachloride (CCl4) induced liver damage in rats. Methods: Twenty-four adult Wistar rats were randomly divided into four groups: group I (normal control) received 0.3 ml/kg/day of propylene glycol for one month; group II (toxicant control) was given 0.7 ml/kg/day of CCl4 dissolved in olive oil (1:1, v/v) orally for 7 days; group III received 5.2 mg/kg/day of LIV for one month followed by CCl4 for one week; group IV received CCl4 for one week and subsequently LIV (5.2 mg/kg/day) was administered for one month. Half of the rats were sacrificed one day after the last treatment, the other half after a 2-week recovery period. Results: The toxicant control group had significantly higher AST and ALT activities, total bilirubin and lower total protein and GSH levels compared to the normal control rats. Similarly, significant increase in serum activities of AST and ALT were observed in group III compared to the normal control rats a day after the last treatment with CCl4, whereas after the recovery period no significant differences were observed in nearly all the parameters. Moreover, group IV showed no significant differences in the parameters mentioned above compared to the normal control rats a day after the last treatment with LIV and after the recovery period. Conclusion: The results of this study indicated that LIV was better as a curative agent rather than a prophylactic agent in rats.

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Anaphe venata entomophagy has previously been implicated in the aetiopathogenesis of seasonal ataxia in humans and altered motor function in rodents. Thus, we investigated the effect of A. venata Phosphate Buffer Saline (PBS) extract on stretching, ataxia and the possible mechanism(s) of action. Animals were divided into four groups (n = 6-12 per group) and graded doses of extract (100, 200 or 400 mg/kg) were administered intraperitoneally (i.p.) while the control group received saline. Behavioral scores were recorded for a period of 30 min immediately after the administration of saline or extract. The role of various receptors in the extract induced stretching and ataxia was evaluated using known receptor antagonists in other groups of rats. The in-vitro cholinesterase inhibition assay of the extract was also performed. The protein profile of the extract was evaluated using the Sodium Dodecyl Sulphate (SDS)-Polyacrylamide gel electrophoresis. Results showed that the extract induced significant (p<0.01) stretching and ataxia behavioural effects dose-dependently when compared to vehicle-treated rats. Pretreatment with the non-selective muscarinic antagonist, scopolamine, significantly (p<0.05) reversed both stretching and ataxia-induced behaviour of PBS extract at all dose levels however both flumazenil and naloxone did not show any significant effects. Anticholinesterase assay also provided evidence that the extract has inhibitory effect on acetylcholinesterase enzyme. Electrophoresis assay suggested that the major proteins in the extract are probably of small molecular weight. In conclusion, the A. venata PBS extract induced-behaviours are probably mediated via the activation of cholinergic-muscarinic receptor systems.

This study sought to investigate the effect of the crude aqueous and phosphate buffer saline (PBS) extracts of Anaphe venata on body scratching behaviour in rat in a novel environment and also to determine the neural mechanism(s) involved. Aqueous and PBS extracts of Anaphe venata were prepared and their effects on body scratching behaviour were evaluated in rats. Animals were divided into four groups (n = 6-12 per group) and graded doses of extracts (100-400 mg/kg) were administered (dissolved in normal saline) intraperitoneally (i.p.) to each animal in the experimental groups. The control group received an equivalent volume of normal saline. Behavioural scores were recorded for a period of 30 minutes after the administration of normal saline or extract. The role of various receptors in the extract induced pruritus was evaluated using known receptor agonist/antagonists. Results showed that aqueous Anaphe extract induced dose-dependent increase in body scratching behaviour (p<0.05) compared to the saline control. This effect was attenuated by scopolamine (3 mg/kg, i.p), flumazenil (2 mg/kg, i.p), and thiamine (1 mg/kg, i.p) while naloxone (2.5 mg/kg, i.p) attenuated body scratching with complete blockade seen at 100 and 200 mg/kg dose levels (p<0.05). PBS extract did not alter body scratching behaviour in the rats. Only the aqueous extract was significantly pruritogenic which was mediated via the muscarinic cholinergic, GABAergic and opioid pathways, while PBS extract did not alter body scratching behaviour.