Objectives: The growing rate of neurological disorders is a major concern in today's scenario. Today's research is focusing on therapeutic interventions providing benefits in these disorders. Presently, drugs of natural origin have gained more interest for the treatment of central nervous system disorders for their efficacy and less/ no side effects. This review is emphasizing the cited roles of Trigonella foenum graecum (fenugreek) and its constituents in different neurological manifestations.Method: A review of the literature, relevant to the role of fenugreek and its major constituents including saponins and alkaloids in different neurological aspects and in delineating the health benefits, was conducted.Results: The cited research acknowledged that fenugreek and its constituents exert positive influence on neurological health. Few studies have reported the beneficial role of fenugreek and its constituents like trigonelline in pathological symptoms of Alzheimer's disease. Similarly, other studies evidenced the neuroprotective, antidepressant, antianxiety as well as modulatory effect on cognitive functions and Parkinson's disease.Discussion: Large populations are the sufferers of the neurological disorders, pointing the need for investigation of such therapeutic interventions which target and delay the underlying pathological hallmarks and exert positive influence on different neurological health problems. Hypolipidemic, hypoglycemic, antioxidant, and immunomodulatory effects of fenugreek and its constituents with their potential role in various neurological disorders were already reported. In future, it would be of even greater interest to further develop more effective dosage, supplementation period, and to evaluate the therapeutic potentials of fenugreek and its constituents in neurological disorders by exploring underlying cellular and molecular mechanisms.
Abstract Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well‐reported consequences of old age‐related disorders like Alzheimer's disease (AD) or dementia. Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Thus, the present study has been designed to examine the role of alendronate against cognitive and neurological disturbances in mice induced by a combined oral dose of d ‐galactose and aluminum chloride (AlCl 3 ) for 6 weeks. d ‐galactose acts as a senescence agent, whereas AlCl 3 is a neurotoxin and in combination generates neuropathologies and cognitive depletion resembling aging and AD. It was found that memory was markedly impaired in d ‐galactose + AlCl 3 ‐treated mice as assessed in different behavioral paradigms. Additionally, d ‐galactose + AlCl 3 led to neurotoxicity assessed on the basis of neuroinflammation, oxidative stress, glial cell activation, neuronal damage, and augmented GSK‐3β level in mice hippocampus. Consequently, alendronate administration orally for 15 days in d ‐galactose + AlCl 3 ‐exposed mice prominently reversed all these behavioral and neuropathological changes. These findings show that alendronate can be a potential therapeutic molecule with multiple targets for the management of age‐related neurological disorders such as AD.
Myocardial infarction is an alarming health issue, needs great attention. The present study investigated the role of histamine-H3 receptor (H3R) agonist imetit in relationship to sympathetic and renin angiotensin system in Wistar rats.Subcutaneous injection of isoproterenol (85 mg/kg) on last 2 consecutive days in per se group and 7 days treatment of different groups at 24 h interval induced myocardial infarction in Wistar rats. H3R agonist imetit (10 mg/kg), H3R antagonist thioperamide (5 mg/kg), losartan (10 mg/kg) were administered orally to evaluate imetit's cardioprotective potential effect by measuring plasma cardiac antioxidant markers, angiotensin II, norepinephrine levels and histopathological analysis.Isoproterenol significantly elevated the angiotensin II and norepinephrine levels in rat plasma. This study revealed that pre-treatment with imetit similar to losartan attenuated norepinephrine and angiotensin II levels whereas thioperamide showed its antagonistic effect by diminishing imetit's effects. Furthermore, its protective effect was confirmed by restoration of cardiac antioxidant markers and histopathological improvement of myocardium integrity.This study confirm imetit's cardioprotective potential and also reveals renin angiotensin system, sympathetic system and H3R correlation in isoproterenol induced toxicity in rats. However, molecular studies must be warranted to prove the role of H3R in myocardial infarction.
Background and Objectives: Curcumin, derived from Curcuma longa, is a well-known traditional medicinal compound recognized for its therapeutic attributes. Nevertheless, its efficacy is hampered by limited bioavailability, prompting researchers to explore the application of nanoemulsion as a potential alternative. Materials and Methods: This study delves into the antihypertensive effects of curcumin nanoemulsion (SNEC) by targeting the renin-angiotensin-aldosterone system (RAAS) and oxidative stress in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. To gauge the cardio-protective impact of SNEC in DOCA salt-induced hypertension, molecular docking was undertaken, uncovering curcumin's high affinity and adept binding capabilities to the active site of angiotensin-converting enzyme (ACE). Additionally, the investigation employed uninephrectomized rats to assess hemodynamic parameters via an AD instrument. Serum ACE, angiotensin II, blood urea nitrogen (BUN), and creatinine levels were quantified using ELISA kits, while antioxidant parameters were evaluated through chemical assays. Result: The outcomes of the molecular docking analysis revealed robust binding of curcumin to the ACE active site. Furthermore, oral administration of SNEC significantly mitigated systolic, diastolic, and mean arterial blood pressure in contrast to the DOCA-induced hypertensive group. SNEC administration also led to a reduction in left ventricular end-diastolic pressure (LVEDP) and an elevation in the maximum rate of left ventricular pressure rise (LV (dP/dt) max). Moreover, SNEC administration distinctly lowered serum levels of ACE and angiotensin II compared to the hypertensive DOCA group. Renal markers, including serum creatinine and BUN, displayed a shift toward normalized levels with SNEC treatment. Additionally, SNEC showcased potent antioxidant characteristics by elevating reduced glutathione, catalase, and superoxide dismutase levels, while decreasing the concentration of thiobarbituric acid reactive substances. Conclusions: Collectively, these findings underscore that curcumin nanoemulsion exerts noteworthy cardio-protective effects through ACE activity inhibition and remarkable antioxidant properties.
Objective: To compare the effect of a combination of sparfloxacin (400 mg) and terfenadine (60 mg) with sparfloxacin (400 mg), terfenadine (60 mg) and placebo on QT Intervals at various RR-intervals in healthy adult male human subjects. Methods: A balanced randomised open-label four treatment, four period four sequence cross over study was performed in 8 healthy male volunteers. Twelve lead ECGs, blood pressure and heart rate were recorded during and Immediate post exercise tests (Bruce Protocol) at 2, 4, 6 and 8 hours after drug administration. QT-intervals were calculated at pre-determined RR-Intervals (400, 500, 600, 700, 800, 900 and 1000 msec) after individual QT-RR fitting. Results: Single oral dose of terfenadine did not prolong the QT-interval duration, while sparfloxacin alone and in combination with terfenadine showed significant prolongation (P<0.05) with an additive interaction only. Conclusion: The prolongation of the QT-interval was caused mainly by sparfloxacin with a small contribution of 60 mg terfenadine.
The aim of the present study was to evaluate the protective effects of alendronate (used in osteoporosis disease) in Triton X-100 (a polyethylene glycol-based non-ionic surfactant)-induced hyperlipidemia in rats.The animals were randomized into seven groups receiving different treatments for 21 days, and alendronate was administered (1.5 and 3 mg/kg body weight, per orally (p.o.) by oral gavage). On day 21, the rats were anesthetized and decapitated, blood samples were extracted, and the livers were dissected for various biochemical tests and histopathological examinations.The biochemical parameters, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), thiobarbituric acid reactive substances (TBARS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and atherogenic index, were increased, and reduction in high-density lipoprotein-cholesterol (HDL-C) levels was observed following Triton X-100 treatment to rats. Alendronate (1.5 and 3 mg/kg) produced a dose-dependent reduction in serum TC, VLDL-C, TGs, ratio of TC/HDL-C, ALT, AST, and TBARS. It significantly increased the HDL-C and superoxide dismutase levels but did not cause a significant decrease in serum LDL-C and/or an increase in catalase levels. Histopathological examinations of alendronate showed beneficial effects with lower capsular thickening, slight enlargement of the hepatocytes at the margin, and lower inflammatory cell infiltration.Alendronate showed dose-dependent antihyperlipidemic and hepatoprotective effects. It may serve a dual purpose as anti-osteoporotic and hypolipidemic by reducing blood cholesterol and TG synthesis and offering hepatic protection.