In recent years, the medical field had significantly progressed to a greater extent which was evidenced with increased life expectancy and decreased mortality rate. Due to the growth of medical field, numerous communicable diseases are prevented and eradicated, whereas the non-communicable disease incidence has been increased globally. One such non-communicable disease which threatens the global population is stroke. Stroke tends to be the second leading cause of death and disability in older population. In lower- and middle-income countries, increased incidence rate of stroke was also evidenced in younger population which is alarming. Lifestyle changes, poor physical activity, stress, consumption of alcohol, oral contraception, and smoking tend to be the causative agents of stroke. Since thrombus formation is the major pathology of stroke, drugs were targeted to thrombolysis. Currently thrombolytic, antiplatelet, and anticoagulant therapies were given for the stroke patients. But the recovery rate of stroke patients with available drugs is very slow. Hence, it is a need of today to discover a drug with increased recovery rate and decreased or nil side effects. Phytochemicals are the best options to treat such non-communicable chronic diseases. Visnagin is one such compound which is used to regulate blood pressure, treat kidney stones, tumors of bile duct, renal colic, and whooping cough. It possesses anti-inflammatory, neuroprotective, and cardioprotective properties; it was also proven to treat epileptic seizures. In this study, the anti-ischemic effect of a furanochrome visnagin was assessed in in vivo rat model. Middle cerebral ischemic/reperfusion was induced in healthy male Sprague Dawley rats and treated with different concentrations of visnagin. The neuroprotective effect of visnagin against cerebral ischemia-induced rats was assessed by analyzing the neurological score, brain edema, infract volume, and Evans blue leakage. The anti-inflammatory property of visnagin was assessed by quantifying proinflammatory cytokines in serum and brain tissues of cerebral ischemia-induced rats. Prostaglandin E-2, COX-2, and NFκ-β were estimated to assess the anti-ischemic effect of visnagin. Histopathological analysis with H&E staining was performed to confirm the neuroprotective effect of visnagin against cerebral ischemia. Our results authentically confirm that visnagin has prevented the inflammation in brain region of cerebral ischemia-induced rats. The neurological scoring and the quantification of PGE-2, COX-2, and NFκ-β prove the anti-ischemic effect of visnagin. Furthermore, the histopathological analysis of hippocampal region provides evidence to the neuroprotective effect of visnagin against cerebral ischemia. Overall, our study confirms visnagin as a potent alternative drug to treat stroke.

Withania somnifera, commonly known as \"Ashwagandha\" or \"Indian ginseng\" is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other plants for the treatment of various illnesses in Indian Systems of Medicine over the period of 3,000 years. Ashwagandha (W. somnifera) belongs to the genus Withania and family Solanaceae. It comprises a broad spectrum of phytochemicals having wide range of biological effects. W. somnifera has demonstrated various biological actions such as anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, anti-arthritic, anti-stress/adaptogenic, neuro-protective, cardio-protective, hepato-protective, immunomodulatory properties. Furthermore, W. somnifera has revealed the capability to decrease reactive oxygen species and inflammation, modulation of mitochondrial function, apoptosis regulation and improve endothelial function. Withaferin-A is an important phytoconstituents of W. somnifera belonging to the category of withanolides been used in the traditional system of medicine for the treatment of various disorders. In this review, we have summarized the active phytoconstituents, pharmacologic activities (preclinical and clinical), mechanisms of action, potential beneficial applications, marketed formulations and safety and toxicity profile of W. somnifera.

Previously we disclosed the discovery of potent Late INa current inhibitor 2 (GS-458967, IC50 of 333nM) that has a good separation of late versus peak Nav1.5 current, but did not have a favorable CNS safety window due to high brain penetration (3-fold higher partitioning into brain vs plasma) coupled with potent inhibition of brain sodium channel isoforms (Nav1.1, 1.2, 1.3). We increased the polar surface area from 50 to 84Å(2) by adding a carbonyl to the core and an oxadiazole ring resulting in 3 GS-462808 that had lower brain penetration and serendipitously lower activity at the brain isoforms. Compound 3 has an improved CNS window (>20 rat and dog) relative to 2, and improved anti-ischemic potency relative to ranolazine. The development of 3 was not pursued due to liver lesions in 7day rat toxicology studies.

BACKGROUND: Croton membranaceus (CM) is used for benign prostate hyperplasia treatment.
OBJECTIVE: Sub-chronic toxicity studies are non-existent and provided the basis for this study.
METHODS: 90 days oral administration of a low dose (LD) (30 mg/kg b. wt.), medium dose (MD) (150 mg/kg b. wt.), and high dose (HD) (300 mg/kg b. wt.) CM aqueous root extract to 3 groups (n=6 each) of male Sprague-Dawley rats, alongside a control group, was undertaken. Urinalysis, hepato-renal function tests, lipid profile, cardiac enzymes, and routine hematology tests were performed.
RESULTS: Triglyceride levels (C=1.05±0.19, LD=0.64±0.08, MD=0.55±0.04, HD=0.50±0.02 mmol/L) were significantly reduced (P<0.05). Very low density lipoprotein (C=0.48±0.09, LD=0.29±0.04, MD=0.25±0.02, HD=0.23±0.01 mmol/L) decreased significantly (P<0.05). Cardiac enzymes-creatinine kinase (C=568±172, LD=315±79, MD=441±209, HD=286±81 IU/L) decreased markedly (P<0.05) alongside lactate dehydrogenase (C=2675±875, LD=1667±1229, MD=1186±442, HD=855±239 IU/L) (P<0.05).
CONCLUSIONS: C. membranaceus aqueous root extract is non-toxic but demonstrates anti-atherogenic and anti-ischemic potentials.