Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors as anti-alzheimer agents via in-silico-based drug design, virtual screening, molecular docking, molecular dynamics simulation, DFT, and non-clinical studies.

Aim: To identify some novel fatty acid hydrolase (FAAH) inhibitors that may contribute to the treatment of Alzheimer's disease (AD).

Methods: In-silico pharmacophore modelling including ligand-based pharmacophore modelling, virtual screening, molecular docking, molecular dynamics modelling, density functional theory and in-silico pharmacokinetics and toxicological studies were employed for the retrieving of novel FAAH inhibitors. Further, these compounds were evaluated for FAAH inhibitory activity using an in vitro enzymatic assay, and later, an in vivo streptozotocin (STZ)-induced AD model was examined in mice.

Does Metabolic Manager Show Encouraging Outcomes in Alzheimer's?: Challenges and Opportunity for Protein Tyrosine Phosphatase 1b Inhibitors.

Protein tyrosine phosphatase 1b (PTP1b) is a member of the protein tyrosine phosphatase (PTP) enzyme group and encoded as PTP1N gene. Studies have evidenced an overexpression of the PTP1b enzyme in metabolic syndrome, anxiety, schizophrenia, neurodegeneration, and neuroinflammation. PTP1b inhibitor negatively regulates insulin and leptin pathways and has been explored as an antidiabetic agent in various clinical trials.

Nyctanthes arbor-tristis Improves Blood Pressure via Endothelial Pathway: In Silico, Ex Vivo, and In Vivo Evidence.

Systemic hypertension, a common metabolic disorder, poses significant health risks despite the availability of antihypertensive drugs. Nyctanthes arbor-tristis has garnered increasing attention for its perceived efficacy and safety, though its mechanisms of action and the bioactive compounds responsible for its antihypertensive effects remain elusive. Therefore, this study aims to elucidate the antihypertensive activity of N.

Aminopeptidase A: A Novel Therapeutic Target for Hypertension Management.

The renin-angiotensin system (RAS) is crucial for regulating and understanding the pathophysiology of hypertension. However, there has been little focus on the breakdown of the active peptide, angiotensin II (AngII). Given that animals lacking aminopeptidase A (APA) exhibit hypertension, it may be concluded that APA is a crucial enzyme in regulating blood pressure by breaking down AngII.

Association Between Type 2 Diabetes Mellitus and Alzheimer's Disease: Common Molecular Mechanism and Therapeutic Targets.

Diabetes mellitus (DM) and Alzheimer's disease (AD) rates are rising, mirroring the global trend of an aging population. Numerous epidemiological studies have shown that those with Type 2 diabetes (T2DM) have an increased risk of developing dementia. These degenerative and progressive diseases share some risk factors.

Water-assisted cascade synthesis of trifluoromethylated dipyridodiazepinone analogues: and antibacterial studies.

A base-promoted palladium-catalyzed cascade reaction is described to access trifluoromethylated dipyridodiazepinone derivatives in an aqueous system (1,4-dioxane-HO). This methodology uses simple chemicals, has a broad substrate scope, is waste minimized (-factor = 0.3-0.

Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight.

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A.

Elucidating the therapeutic mechanism of betanin in Alzheimer's Disease treatment through network pharmacology and bioinformatics analysis.

Betanin, a natural compound with anti-inflammatory and antioxidant properties, has shown promise in mitigating Alzheimer's disease (AD) by reducing amyloid plaque production. Employing network pharmacology, this study aimed to elucidate betanin's therapeutic mechanism in AD treatment. Through integrated analyses utilizing SwissTargetPrediction, STITCH, BindingDB, Therapeutic Target Database (TTD), and OMIM databases, potential protein targets of betanin in AD were predicted.

Anti-Depressant Like Effects of Aethoscytus Foveolus Oil by Improving Stress-mediated Alterations of Monoamine Oxidase, Oxidative Stress, and Neuroinflammation In-vivo.

Depression is a neuropsychological disorder with a complex pathophysiology and its pharmacotherapy is compromised by adverse side effects. Addressing the need for effective treatment for depression, the current study aims to characterize the antidepressant activity of oil extract derived from Aethoscytus foveolus, bugs that are widely available in India, in a mice model of stress-induced depression. Chemical moieties characterized by GC-MS of A.

Tissue regeneration properties of hydrogels derived from biological macromolecules: A review.

The successful tissue engineering depends on the development of biologically active scaffolds that possess optimal characteristics to effectively support cellular functions, maintain structural integrity and aid in tissue regeneration. Hydrogels have emerged as promising candidates in tissue regeneration due to their resemblance to the natural extracellular matrix and their ability to support cell survival and proliferation. The integration of hydrogel scaffold into the polymer has a variable impact on the pseudo extracellular environment, fostering cell growth/repair.

Predictive Modelling in pharmacokinetics: from in-silico simulations to personalized medicine.

Introduction: Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning and in-silico predictions, scarcity of data hampers accurate prediction of drug candidates' pharmacokinetic properties.

Areas Covered: The study highlights current developments in human pharmacokinetic prediction, talks about attempts to apply synthetic approaches for molecular design, and searches several databases, including Scopus, PubMed, Web of Science, and Google Scholar.

Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats.

Ethnopharmacological Relevance: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy.

Decalepis hamiltonii root fraction alleviates CCl hepatotoxicity in a rat model.

Background: Decalepis hamiltonii (D. hamiltonii) is Indian folk medicine in herbal preparations, to reduce appetite, and cures dysentery, bronchitis, uterine hemorrhage, and other ailments.

Objective: The current investigation focused on the hepatoprotective effect of D.

Mitochondrial transfer restores impaired liver functions by AMPK/ mTOR/PI3K-AKT pathways in metabolic syndrome.

Aim: We investigated the effect of mitochondria transfer in high fat diet and streptozotocin (HFD + STZ) induced metabolic syndrome (MeS) in rats. The effect of mitochondria transfer in MeS with co-existing hypertension, hyperlipidaemia, diabetes and fatty liver together, has not been reported.

Materials And Methods: Heathy mitochondria was transferred intravenously and the effect on several physiological parameters and biochemical parameters were examined in HFD + STZ rats.

A review on therapeutic mechanism of medicinal plants against osteoporosis: effects of phytoconstituents.

Osteoporosis is a metabolic bone disorder that over time results in bone loss and raises the risk of fracture. The condition is frequently silent and only becomes apparent when fractures develop. Osteoporosis is treated with pharmacotherapy as well as non-pharmacological therapies such as mineral supplements, lifestyle changes, and exercise routines.

Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes.

The glucokinase regulator (GCKR) gene encodes an inhibitor of the glucokinase enzyme (GCK), found only in hepatocytes and responsible for glucose metabolism. A common GCKR coding variation has been linked to various metabolic traits in genome-wide association studies. Rare GCKR polymorphisms influence GKRP activity, expression, and localization.

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

Background: Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma.

Targeting Neuroinflammation as Disease Modifying Approach to Alzheimer's Disease: Potential and Challenges.

Alzheimer's disease (AD) is the most common form of dementia, having characteristic clinical features of progressive memory loss and visuospatial, language, and cognitive impairment. In addition, patients often suffer from comorbid depression and aggression. Aging is a major contributing factor, though the exact pathophysiological involvement in the disease progression is debatable.

Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome.

Ethnopharmacological Relevance: In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females.

Aim: The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats.

Approaches to Address PK-PD Challenges of Conventional Liposome Formulation with Special Reference to Cancer, Alzheimer's, Diabetes, and Glaucoma: An Update on Modified Liposomal Drug Delivery System.

Liposomes nowadays have become a preferential drug delivery system since they provide facilitating properties to drugs, such as improved therapeutic index of encapsulated drug, target and controlled drug delivery, and less toxicity. However, conventional liposomes have shown some disadvantages, such as less drug loading capacity, poor retention, clearance by kidney or reticuloendothelial system, and less release of hydrophilic drugs. Thus, to overcome these disadvantages recently, scientists have explored new approaches and methods, viz.

GSK-3β and its Inhibitors in Alzheimer's Disease: A Recent Update.

Alzheimer's disease (AD) is an emerging major health and socioeconomic burden worldwide. It is characterized by neuronal loss, memory loss and cognitive impairment in the aging population. Despite several scientific advancements over the past five decades, the underlying molecular mechanism of the disease progression is yet unknown.

Repurposing of digoxin in pain and inflammation: An evidence-based study.

In recent years, the drug repositioning strategy has gained considerable attention in the drug discovery process that involves establishing new therapeutic uses of already known drugs. In line with this, we have identified digoxin a cardiac glycoside, as a potent inhibitor of soluble epoxide hydrolase (sEH) enzyme employing in silico high throughput screening protocols and further confirmed using in vitro cell-free sEH inhibitory assay and in vivo preclinical studies in rodents for its repurposing in hyperalgesia, inflammation, and related disorders. Oral administration of digoxin at dose 0.