Central nervous system agents in medicinal chemistry最新文献

Aim: We aimed to conduct in silico screening of the potential phytoconstituent from a natural product database to find SIRT2 inhibitors.

Background: Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by behavioral and mental symptoms as well as a progressive loss of cognitive ability. Since SIRT2 may be detrimental to neurological illnesses, it is a prime target for research into SIRT2 inhibitors.

Objective: To identify the SIRT2 inhibitors and their role in AD.

Methods: We have utilized NPAtlas database and screened using pharmacophore-based virtual screening, molecular docking, and simulation. The Natural Products Atlas provides unrestricted access to various natural products derived from bacteria and fungi, allowing researchers to investigate and visualize the extensive chemical diversity in the natural world.

Results: From in silico screening data, we have found phytoconstituents that could function as SIRT2 inhibitors. Six phytoconstituents were identified using pharmacophore-based virtual screening. According to molecular docking, Kurasoin B outperformed the reference molecule regarding binding energy. Kurasoin B exhibited a binding affinity of -12.543 kcal/mol, whereas the binding affinity of the reference molecule was -12.089 kcal/mol. The Kurasoin B complex with SIRT2 was determined to be stable throughout the simulation by performing MD simulation, with an RMSD of 2.88 (Å), whereas the reference and free protein displayed RMSDs of 3.74 and 4.70 (Å), respectively.

Conclusion: In silico studies and data analysis, suggest that Kurasoin B may be able to suppress the SIRT2 protein for managing AD.

Many disorders, including heart, bone, cancer, liver, and brain disease, have been treated using stem cell therapy as a viable alternative. The somatosensory system is affected by a lesion, which leads to neuropathic pain (NP), and just a relatively tiny fraction of patients now receive effective care from existing pharmacological medications. There have been studies to show the effectiveness of various stem cells in reducing or treating experimental neurological pain, although these studies are uncommon in number. In this review, we will summarize the preclinical and clinical research that has been conducted on the effectiveness of several stem cell types, such as mesenchymal stem cells, bone-derived stem cells, and neural stem cells, in reducing neurological pain in this study.

Background: Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs.

Objective: The aim of this study was to present a systematic review of the association between infections, seizures, and drugs.

Methods: From their inception to 18 February 2024 relevant in-depth consequent guide approach and the evidence-based choice were selected associated with a knowledgeable collection of current, high-quality manuscripts.

Results: Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring.

Conclusion: Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.

Objective: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus.

Materials and methods: Prolonged dosing of AlCl3(7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue.

Results: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCll3 effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCll3, thereby maintaining the typical histoarchitectural arrangement of these regions.

Conclusion: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCll3 exposure.

Background: Neuropathic pain is a complex chronic condition resulting from the damage or dysfunction of the nervous system. Conventional therapies offer limited success and often come with various adverse effects. Therefore, the exploration of alternative therapies, such as phytoconstituents, may be of substantial interest for their potential to alleviate neuropathic pain.

Objectives: This review systematically examines the diverse roles and mechanisms of various phytoconstituents in modulating neuropathic pain. In this study, a comprehensive analysis of phytoconstituents in neuropathic pain is carried out to understand their mechanism in preventing the disease.

Methods: The current search is done in the databases of Google Scholar, PubMed Central, ScienceDirect, and Scopus using the keywords: neuropathic pain, phytoconstituents as analgesics, physiological effects of medicinal plants, and natural products, to find the most relevant articles of the last 10 years.

Results: Out of 125 articles, 112 were included in this study, which revealed that several phytoconstituents inhibit several biomarkers responsible for neuropathic pain. Moreover, this review highlights the underlying molecular pathways and targets through which these bioactive compounds exert their therapeutic effects, emphasizing their potential as novel pharmacological agents.

Conclusion: This study concludes that phytoconstituents may possess potential applications in managing neuropathic pain and could be effectively used as an alternative approach to mitigate the condition with enhanced risk of safety and tolerability.

Flavonoids have a wide range of neuroprotective effects on the brain, including the capacity to reduce neuroinflammation, shield neurons from harm caused by neurotoxins, and maybe improve memory, learning, and cognitive function. These functions are most likely a result of two similar mechanisms. Inhibiting neurotoxic substance-induced apoptosis and promoting synaptic plasticity and neuronal survival are achieved by first interacting with key protein and lipid kinase signaling pathways in the brain. Second, they have positive effects on the vascular system that alter cerebrovascular blood flow and can result in angiogenesis, neurogenesis, and morphological alterations in neurons. Through these pathways, eating foods high in flavonoids has the potential to avoid or delay age-related impairments in cognitive abilities as well as neurodegeneration. Due to the high level of interest in creating new pharmaceuticals that might improve the cognitive function of the brain, Flavonoids could be important preparatory substances in the development of a new class of brain-improving drugs.

More than 20 million people worldwide have Alzheimer's disease (AD), making it the most prevalent disease. Patients with AD may live for at least a decade after diagnosis, making it the most common cause of disability in the elderly. Each year, 1% to 4% of the population is affected by AD, with prevalence peaking between ages 65 and 70 and declining to 6% among those over 85. Researchers have accumulated evidence on medicinal herbs that may reverse the pathogenesis of Alzheimer's disease. Alzheimer's disease (AD) is associated with severe memory loss, which can negatively impact social and professional life. The first neurotransmitter linked to Alzheimer's was acetylcholine (ACh). There is no known cure, and the available treatments are ineffective. Multiple studies indicate that Ayurvedic restorative herbs and their constituents may be effective in treating Alzheimer's disease. This technique emphasizes the fact that delaying or preventing Alzheimer's disease with the help of natural bio-actives could reduce the number of cases over the next half-century. To provide detailed information, the pathology and pathophysiology of Alzheimer's Disease are discussed in the text of this review, along with an overview of the neurotransmitters involved in the progression of the disease. The importance of different natural bioactives for the treatment of Alzheimer's disease is also outlined in the paper. The information contained in this paper can serve as a template for future research expressing the more beneficial role of other bioactive in acting as an adjuvant in the prevention and treatment of this disease, facing certain challenges and gaps with conventional drugs used to treat Alzheimer's disease.

The microbiota that inhabits the gastrointestinal tract has been linked to various gastrointestinal and non-gastrointestinal disorders. Scientists have been studying how the bacteria in our intestines have an effect on our brain and nervous system. This connection is called the "microbiota-gut-brain axis". Given the capacity of probiotics, which are live non-pathogenic microorganisms, to reinstate the normal microbial population within the host and confer advantages, their potential impact has been subjected to scrutiny with regard to neurological and mental conditions. Material sourced for this review included peer-reviewed literature annotated in the PubMed, Web of Science, Scopus, and Google Scholar databases. The result has indicated the integration of probiotics into a child's diet to enhance the neuro-behavioral symptoms. Notwithstanding this, the current data set has been found to be insufficient and inconclusive. The potential utility of probiotics for the prevention or treatment of neurologic and mental disorders has become a subject of substantial interest.

Introduction and aims: Seizures due to epilepsy in any form cause a wide range of problems in a patient's physical, psychological, and social health. This study aimed to investigate piperine's anti-seizure and antiepileptic effects and mechanisms.

Methods: In this systematic review study, which was conducted according to the principles of PRISMA 2020, the initial search was conducted on November 2, 2023, using EndNote software. Various databases such as PubMed, Cochrane Library, Web of Science, Embase, and Scopus were searched using specific keywords. After screening the articles, a form was designed according to the objectives of the study, and the information related to the included articles was entered in the form, and the studies were reviewed.

Results: Piperine showed its antiepileptic activity by affecting the brain's antioxidant, anti-inflammatory, and anti-apoptotic activity. It also, by modulating brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA)ergic activity, can control seizures. In addition, piperine can help treat seizures and epilepsy by elevating 5-HT levels in the brain, modulating astrocyte and microglia function, modulatory effects on Ca²⁺ and NA⁺ channels, increasing antiepileptic drugs bioavailability and influencing protein and gene expression.

Conclusion: In vivo and in vitro studies showed beneficial effects on treating epilepsy. Although clinical studies also showed similar results, these needed to be increased, and more clinical studies needed to be designed in this field.