Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes.
View Article and Find Full Text PDFTreatment of skin cancer demands targeted delivery without minimal systemic circulation for maximum therapeutic window. Dermal delivery with nano-formulation offers such advantages. Therefore, present study aims to formulate Lyotropic liquid crystalline nanoparticles (LLC NPs) loaded with Apigenin (API) for dermal delivery using quality by design (QbD) approach for effective permeation resulting in improved bioavailability.
View Article and Find Full Text PDFAlzheimer's disease is identified by pathological hallmarks such as intracellular neurofibrillary tangles (NFTs) and extracellular amyloid β plaques. Several hypotheses exist to define the neurodegeneration including microglial activation associated with neuroinflammatory processes. Recently, pharmacological inhibition of endocannabinoid (eCB)-degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), is being investigated to modulate the pathology of Alzheimer's disease.
View Article and Find Full Text PDFThe primary prophylaxis with filgrastim (FIL) and pegfilgrastim (PEG-F) is recommended to decrease the severity of chemotherapy-induced neutropenia (CIN). The commonly reported adverse drug reactions (ADRs) with FIL and PEG-F is bone pain. ADRs pertaining to FIL and PEG-F were extracted from the European EudraVigilance (EV) database.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a neurological disease that gradually causes memory loss and cognitive impairment. The intracellular secondary messenger cyclic nucleotide cAMP helps in memory acquisition and consolidation. In several models of AD, increasing their levels using phosphodiesterase (PDE) inhibitors improved cognitive performance and prevent memory loss.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most devastating neurodegenerative disorder, accounting over 46 million cases of dementia globally. Evidence supports that Brain Insulin Resistance (BIR) due to serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1) has an association with AD. GLP-1 an incretin hormone, rapidly degraded by Dipeptidyl Peptidase-4 (DPP-4) has also confirmed its efficacious role in AD.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most prevalent age-dependent neurodegenerative disease characterized by progressive impairment of memory and cognitive functions. Cyclic nucleotides like cAMP and cGMP are well-known to play an important role in learning and memory functions. Enhancement of cAMP and cGMP levels in the hippocampus by phosphodiesterase (PDE) inhibitors might be a novel therapeutic approach for AD.
View Article and Find Full Text PDFNeurological 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 ) for 6 weeks.
View Article and Find Full Text PDFThe current study aimed to develop alendronate (ALN)-loaded chitosan nanoparticles (CS-ALN-NPs) for brain delivery intranasal route. These CS-ALN-NPs reduced the peripheral side effects and released ALN directly to brain. These NPs were formulated through ionic gelation technique by mixing sodium tripolyphosphate (1.
View Article and Find Full Text PDFObesity and consumption of diet rich in fat are known to contribute to the development of Alzheimer's disease (AD) which is a complex and multifactorial neurodegenerative disease and a leading cause of mortality with unmet medical needs. Hypercholesterolemia was discovered to increase neuropathological changes along with cognitive decline in AD mouse models but still the underlying mechanism is elusive. Furthermore, isoprenoids, the crucial products of Mevalonate-pathway produced by the action of farnesyl pyrophosphate synthase (FPPS) enzyme, are also demonstrated to play a key role in AD.
View Article and Find Full Text PDFThe World Health Organization (WHO) has ranked depression the 4 leading cause of disability worldwide. Thymoquinone (TQ), is an active constituent of having various medicinal properties but has poor solubility and bioavailability. This problem was overcome by developing nanoformulation of TQ.
View Article and Find Full Text PDFBackground: Excessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.
View Article and Find Full Text PDFBackground And Aim: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk.
Methods: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019.
Today, neurological disorders such as epilepsy, depression, tardive dyskinesia, and stress, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, dementia, and Huntington's disease affect millions of people all over the world. Existing pharmacological interventions do not meet the desired therapeutic benefits for a significant number of patients, and hence, numerous research studies are in progress to find novel therapies for these disorders. Herbal drugs, which have been used in traditional medicine for centuries, are also being explored and scientifically evaluated for the treatment of these neurological disorders.
View Article and Find Full Text PDFBackground: Currently, a large number of people throughout the world are affected by neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease which appear with a lapse in recall, attention and altered cognitive functions. Learning and memory, the fundamental indices defining cognitive functions, are the complex psychological processes governing acquisition, consolidation, and retrieval of stored information. These processes are synchronized by the coordination of various parts of the brain including hippocampus, striatum and amygdala.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most prevalent age related neurodegenerative disorder manifested by progressive cognitive decline and neuronal loss in the brain, yet precise etiopathology of majority of sporadic or late-onset AD cases is unknown. AD is associated with various pathological events such as Aβ deposition due to BACE-1 induced cleavage of APP, neuroinflammation, increased cholesterol synthesis, cholinergic deficit and oxidative stress. It was found that bone drug, alendronate (ALN) that cross blood brain barrier inhibits brain cholesterol synthesis and AChE enzyme activity.
View Article and Find Full Text PDFNeurodegenerative disorders and osteoporosis share some common underlying pathological features including calcium overload, accumulation of toxic chemicals, inflammation and impaired protein prenylation by isoprenoids (farnesyl pyrophosphate and geranylgeranyl pyrophosphate) appear later stage of life. Substantial number of pre-clinical and clinical reports as well as in vitro data univocally acknowledged the negative impact of altered post-translational modification (prenylation) of proteins like small GTPases (Rffhes, Rho, Rac etc.) and cholesterol levels in both serum and brain on CNS integrity.
View Article and Find Full Text PDFVascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaD in experimental rats. VaD was induced by BCCAO in rats and betulinic acid (10 and 15 mg/kg/day po) was administered 1 week after surgery.
View Article and Find Full Text PDFBackground: There has been conflicting reports on the effect of third generation aromatase inhibitors on cognition in estrogen-deficient states. Since aromatase inhibitors themselves cause estrogen deprivation, the present work was designed to evaluate the comparative effect of three aromatase inhibitors on behavioral measures of learning and memory in female mice. Further, in view of the reports of estrogen and Wnt signaling pathway in cognition, the role of two Wnt signaling antagonists (dickkopf-1 and sclerostin) in mediation of cognitive effects of aromatase inhibitors was evaluated.
View Article and Find Full Text PDFObjectives: 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.
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