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Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults, imposing psychological, cognitive, social and also economic burdens to the sufferer. Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials throughout the central nervous system. Dysfunction of these channels has been implicated in the pathogenesis of epilepsy. VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures, and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies. We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic, acquired and pharmacoresistant forms of epilepsy in this review. We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies. The current anti-seizure medications (ASMs) especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects. Therefore, there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms, to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.

Background The risk factors of metabolic syndrome (MS) precedes the development of cardiovascular disease and type 2 diabetes and are largely triggered by high-carbohydrate high-fat diet (HCHFD) and sedentary lifestyle. The development of these risk factors is connected to persistent low-grade inflammation. Though, ursolic acid (UA) has been shown to prevent HCHFD-induced metabolic parameters. The present study aimed to elucidate the molecular mechanisms underlying the preventive effects of dietary UA supplementation on obesity-related metabolic disorders and inflammation in male Wistar rats fed with HCHFD. The animals were randomly divided into 4 groups (n = 5): 1—normal diet (ND) + distilled water (DW); 2—ND + UA; 3—HCHFD + DW; 4—HCHFD + UA. HCHFD was augmented with 20% fructose in drinking water. The animals were fed their respective diets daily for 20 weeks. 250 mg/kg body weight of ursolic acid was administered orally to UA-treated groups for the last 8 weeks. Blood samples were collected and liver and adipose tissues were harvested for biochemical and tissue analysis, respectively. Results BMI and FBG were significantly lowered in the HCHFD + UA-fed animals compared to the HCHFD + DW-fed animals. In the HCHFD + UA-fed animals, HOMA-IR, serum insulin, cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) were significantly decreased while high-density lipoprotein cholesterol (HDL-C) was increased compared to the HCHFD + DW-fed animals. UA significantly decreased serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and increased adiponectin level compared to the HCHFD + DW-fed animals. The messenger ribonucleic acid (mRNA) level of peroxisome proliferator activated receptor-gamma (PPAR-γ) in adipose tissue was significantly upregulated while liver PPAR-γ mRNA level was significantly downregulated in HCHFD + UA-fed animals compared to HCHFD + DW group, respectively. UA restored the architecture of liver parenchyma to near normal. Conclusion Dietary UA supplementation mitigated metabolic dysfunction and inflammation associated with obesity via modulation of liver and adipose tissue PPAR-γ in male Wistar rats fed with HCHFD for 20 weeks.

Diabetes mellitus is a metabolic disorder that can lead to various complications affecting the heart, kidney, and eye. Several synthetic and natural products have been used for disease management, but the disease still remains a global challenge. The use of plants as an alternative management for diabetes has been on the rise. Regrettably, the comprehensive repository is not available to guide future research in the area of plants with a related mechanism of action for the development of an effective drug. To identify and compile medicinal plants frequently used with proven scientific hypoglycaemic properties and their possible modes of action. This was done through a literature search of scientific databases using search tools like DOAJ, EMBASE, Europe PMC, FSTA, Google Scholar, HubMed, Indian Citation Index, Medline Plus, Merck Index, PubMed, ScienceDirect, Science3open, Science Open, SciFinder, Scirus, Core, Scopus, Semantic Scholar, Shodhganga, and World Wide Science. Search keywords included: medicinal plants, antidiabetics, hypoglycaemic, alpha-amylases/glucosidase inhibition, glucose metabolic enzymes, antihyperglycaemia, insulin secretion/surrogate, β-cell amelioration, phytochemicals, diabetes management, anti-oxidant, and enhance glucose transporters. The study excludes plants used in the management of diseases other than diabetes mellitus. From the search, 611 authenticated medicinal plants with anti-diabetic properties were eligible and grouped according to their reported probable mode of action. Precisely 20.6% of the plants exhibited their anti-diabetic effect via prevention of oxidative stress; 11.6% acted through stimulation of insulin secretion, inhibition of insulin degradation, and reduction of insulin resistance. Also, 10.8% inhibited enzymes of carbohydrate gastrointestinal digestion, 2.8% were postulated to regulate enzymes of glucose metabolism, and 54.2% acted via nonspecific or multiple means, as well as those whose anti-diabetic mode of action was yet to be identified. This study has shown that the exact mechanisms or mode of action of the majority of plants with hypoglycaemic properties are yet to be explored. Scientists would therefore find this paper useful in their future research. This paper may also serve as a potential lead for the easy harmonization of plants with a related mode of action in the drug discovery process targeted at the management of diabetes mellitus. Graphical abstract