Introduction: The behavioral sensitization (BS) model for psychostimulants is the most developed framework for explaining the occurrence of drug-induced psychoses. However, there is limited data on the potential of synthetic cathinones (SCs) to induce BS, which restricts the model’s full application in understanding this phenomenon. Aim: This study aimed to provide theoretical evidence regarding the potential of synthetic cathinones to inhibit the dopamine membrane transporter at levels sufficient to induce behavioral sensitization. Methods: The following SCs were selected as ligands: 4-methylmethcathinone (mephedrone), 3,4- methylenedioxypyrovalerone (MDPV), and alpha-pyrrolidinovalerophenone (alpha-PVP). Amphetamine and cocaine were included for comparison. Molecular docking was performed using Auto- Dock Vina and the Attracting Cavities algorithms. The human dopamine transporter structure was obtained from the Protein Data Bank (PDB ID: 8Y2DS). Additionally, PubMed, CNKI, and eLibrary databases were searched to compare the docking results with experimental data from cell lines and animal studies; 13 publications were included in the analysis. Results: All synthetic cathinones studied showed no significant differences in binding affinity to the orthosteric site of the dopamine membrane transporter, suggesting that they may act similarly to amphetamine and cocaine. These findings were corroborated by experiments in cell lines. For mephedrone and MDPV, the potential to induce behavioral sensitization (BS) was also confirmed in animal studies. Conclusion: Theoretically, mephedrone, MDPV, and alpha-PVP can inhibit the dopamine membrane transporter, leading to increased extracellular dopamine levels and promoting the development of dopamine hypersensitivity and behavioral sensitization.
Abstract: Neuro-psychiatric disorders represent one of the most complex and pressing challenges in modern medicine. These conditions, ranging from schizophrenia and Parkinson’s disease to Alzheimer’s and mood disorders, are characterized by multifactorial etiologies, overlapping symptomatology, and often unpredictable therapeutic responses. Despite decades of research, the pharmacological management of these disorders remains suboptimal, with many patients experiencing limited efficacy, delayed onset of action, or debilitating side effects. A growing body of evidence points to shared pathological mechanisms across neurodegenerative and psychiatric conditions, including intracerebral protein aggregation, mitochondrial dysfunction, abnormal iron accumulation, oxidative stress, and ferroptosis-induced neuronal death. These converging pathways underscore the need for therapeutic strategies that go beyond symptomatic relief to address underlying molecular dysfunctions. In this context, this thematic issue brings together a collection of cutting-edge research articles that reflect the latest advances in drug design, development, and delivery strategies to improve therapeutic outcomes in neuropsychiatric care. This issue is a curated effort to bridge the gap between molecular innovation and clinical translation. It highlights how interdisciplinary approaches spanning medicinal chemistry, pharmacogenomics, molecular docking, and natural product research are converging to redefine the therapeutic landscape. From enzyme-targeted therapies and marine-derived neuroprotectants to prolactin-sparing antipsychotics and precision medicine frameworks, each manuscript contributes a unique perspective to this evolving field. Collectively, these studies illuminate promising avenues for personalized, mechanism-based interventions that may transform the future of neuropsychiatric treatment. This issue aspires to serve not only as a scholarly resource but also as a catalyst for innovation and collaboration across disciplines.
Background: Scutellarein, a bioactive flavone derived from Scutellaria barbata D. Don—a herb widely used in Traditional Chinese Medicine (TCM)—is known for its neuroprotective, neurogenic, and anti-inflammatory properties. Our previous research demonstrated that the hydroethanolic extract of S. barbata (HSBE) exhibits robust antidepressant-like activity, supported by behavioral, neurochemical, and biochemical alterations in rodent models. Furthermore, a validated High-Performance Thin-Layer Chromatography (HPTLC) method confirmed the presence of scutellarein in significant amounts within the extract. Based on these findings and existing literature, the present study was designed to investigate the antidepressant-like potential of scutellarein and elucidate its molecular mechanisms. Method: Swiss albino mice were orally administered scutellarein at doses of 20 and 40 mg/kg body weight for three weeks. The CUMS method was employed to induce depression for 21 days. On the 21st day, TST, FST, and OFT were used to evaluate antidepressant-like potential. On the 22nd day, 5-HT, NE, and DA levels were quantified in the cortex, hypothalamus, and hippocampus. MAO-A and B activity, as well as levels of antioxidant enzymes, were assessed in the brain. Additionally, plasma corticosterone and nitrite levels were also measured to elucidate the mechanisms of action. Results: Scutellarein exhibited dose-dependent antidepressant-like effects in both TST and FST, with enhanced locomotor activity observed in the OFT, indicating improved mood and mobility. Furthermore, scutellarein significantly modulated levels of NE, 5-HT, and DA in key brain regions. Additionally, it regulated MAO-A and B activity, as well as antioxidant enzyme levels, potentially affecting neurotransmitter levels and mitigating oxidative stress. Scutellarein also affected plasma nitrite and corticosterone levels, indicating systemic impact on nitric oxide signaling and the HPA axis, which are key in stress responses. Discussion: The findings suggest that scutellarein exerts antidepressant-like effects through a multimodal mechanism involving monoaminergic regulation, attenuation of oxidative and nitrosative stress, inhibition of MAO activity, and modulation of HPA axis function. These combined actions support the neurobiological relevance of scutellarein in stress-induced depression. Conclusion: Scutellarein demonstrates significant antidepressant-like activity in vivo and may represent a promising phytochemical candidate for further development as a novel antidepressant agent.
Introduction:: Emotional blunting—i.e., a subjective reduction in emotional range and intensity—is frequently reported during SSRI treatment and may hinder full functional recovery in major depressive disorder (MDD). Esketamine, a rapid-acting glutamatergic antidepressant approved for treatment-resistant depression (TRD), may exert antidepressant benefits while preserving emotional responsiveness. Methods:: We conducted a two-arm, naturalistic observational study including 60 adults with TRD (SSRI monotherapy, n=30; adjunctive intranasal esketamine, n=30). Emotional blunting and emotional intensity were assessed at baseline and week 4 using the Oxford Depression Questionnaire (ODQ), the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA), the Laukes Emotional Intensity Scale (LEIS), and the Self-Assessment Manikin (SAM). Depressive symptoms were measured with the Montgomery–Åsberg Depression Rating Scale (MADRS). Between- group comparisons used independent-samples t-tests with effect-size estimation. Results:: Both groups improved in depressive symptoms, with a significantly greater MADRS reduction in the esketamine group (−16.7 vs −5.4 points; p< 0.0001). Compared with esketamine, SSRI-treated patients reported higher emotional blunting (ODQ and OQESA; p< 0.0001) and lower emotional intensity/valence (LEIS and SAM; p< 0.0001). Discussion:: Adjunctive esketamine was associated with both superior antidepressant improvement and a more preserved emotional experience than SSRI monotherapy. Conclusion:: In TRD, adjunctive intranasal esketamine was associated with reduced emotional blunting and greater symptom improvement versus SSRI monotherapy, supporting routine assessment of emotional side effects in treatment planning.
Abstract: Depression remains a leading cause of global disability, imposing substantial personal, social, and economic burdens worldwide. Although advances in pharmacotherapy and evidencebased psychotherapies have improved outcomes, many individuals do not achieve adequate or sustained remission, prompting interest in complementary and non-pharmacological approaches. Chromotherapy, which involves exposure to specific colors or light spectra with the aim of influencing mood and psychological well-being, has gained renewed attention as a potential adjunctive intervention. This review critically examines the historical evolution, theoretical foundations, and current clinical evidence regarding chromotherapy in depressive disorders. Proposed mechanisms include circadian rhythm modulation, potential neurochemical effects, psychophysiological relaxation, and psychologically mediated symbolic associations with color; however, several explanatory models remain speculative, particularly those framed within symbolic or “energy-based” paradigms. While preliminary, culturally contextualized reports suggest possible mood-related benefits, the empirical evidence remains limited and methodologically heterogeneous, with small sample sizes and insufficient controls, limiting firm conclusions. Ethical considerations—including informed consent and avoidance of substituting unvalidated therapies for established treatments—are also discussed. Overall, current evidence does not support chromotherapy as a replacement for validated psychiatric interventions, but rigorously designed future studies incorporating standardized protocols and neurobiological measures are needed to determine whether it holds adjunctive value within modern mental health care.
Depression remains one of the most burdensome global mental health conditions, disproportionately impacting women due to gender roles, societal expectations, and workplace inequalities, and other intersecting factors. In Lebanon and the broader Arab region, the increasing participation of women in the workforce contrasts with cultural norms that traditionally position them as homemakers. However, little is known about how these challenges contribute to depression among working mothers in Lebanon. This cross-sectional study assessed the prevalence of depression among Lebanese working mothers aged 18 and older between June and October 2019. Data were collected using a selfadministered survey, incorporating sociodemographic information and Beck's Depression Inventory (BDI). Statistical analyses were conducted using the Statistical Package for Social Sciences (IBM SPSS, version 21). Based on BDI scores, 36.3% of the 405 participants exhibited depression, with severity ranging from borderline to extreme. Protective factors included engaging in exercise, yoga, or meditation (OR=0.62, p=0.015). Conversely, women with a prior depression diagnosis (OR=2.79, p=0.002) or psychological trauma within the past three years (OR=2.93, p<0.001) had significantly higher odds for depression. Work-related stressors, specifically employment for reasons other than personal fulfillment (OR=2.55, p<0.001) and job-home conflicts (OR=2.53, p<0.001), were also associated with an increased risk. The findings underscore the urgent need for workplace interventions, mental health policies, and cultural shifts to help working mothers in Lebanon and the Arab region balance their professional and family responsibilities.
Cognitive enhancers, also known as nootropics, have spiked in popularity in recent years, leading to rising use of these substances with unclear guidelines on their efficacy and safety. This review aims to evaluate the effectiveness and safety of over-the-counter nootropics in enhancing various cognitive functions, such as memory and attention. The existing literature surrounding cognitive enhancers has focused predominantly on their cognitive enhancing abilities in individuals with cognitive impairments with limited clinical evidence on their role in healthy individuals. To address this gap, a comprehensive review of several widely used over-the-counter cognitive enhancers was conducted, excluding stimulant and prescription substances, focusing on their mechanism of action and safety profiles. The cognitive enhancers that were reviewed can be grouped into five different classes, including herbs, amino acids, acetylcholinesterase inhibitors, cholinergic enhancers, and vitamins. It was found that while some cognitive enhancers have shown promising results in specific cognitive domains, there is still more research needed to support their widespread use with more focus on clinical trials to validate their long-term benefits and safety.
Lithium counteracts impulsivity and aggression in affective disorders, two emotion-related facets of inhibitory control. This raises the question of whether lithium also affects inhibitory processes in the cognitive domain. This narrative review examines experimental groups of patients receiving lithium, either as monotherapy or as part of multitherapy, compared with patients on other medications or healthy controls. Patients taking lithium alongside other medications performed worse than healthy controls on the Trail Making Test B, Stroop Color-Word Test, and Wisconsin Card Sorting Test. Similarly, those on lithium monotherapy also underperformed compared to healthy controls on the Trail Making Test B and Stroop Color-Word Test. However, their performance on the Wisconsin Card Sorting Test was less impaired. The inhibitory processes assessed by the Trail Making Test B and Stroop Color-Word Test appear to be particularly susceptible to the effects of lithium. The apparent vulnerability in performance on the Trail Making Test B and Stroop tests needs to be confirmed with studies that include placebo controls.
Epilepsy is a persistent and intricate condition, standing as one of the most prevalent neurological disorders globally, impacting approximately 50 million individuals. The employment of nanomedicines has emerged as a promising strategy to administer drugs to the brain, thereby enhancing their therapeutic ratio. The complexity of epilepsy lies in its inheritance and etiology, which involve a multitude of genetic and epigenetic mechanisms. A multitude of medications are presently being examined in the realm of clinical practice, encompassing those that possess a mechanism analogous to that of renowned antiseizure medications (ASMs), such as the agonists of the GABA-A receptor, as well as those with innovative mechanisms, exemplified by the activation of melatonin receptors. This article explores innovative therapies for epilepsy management, focusing on nanoparticles, such as liposomes, polymeric nanoparticles, and dendrimers, which can be engineered to encapsulate and release antiepileptic drugs (AEDs) with exceptional precision. By functionalizing these nanoparticles with targeting ligands, they can be directed specifically to epileptic brain regions, minimizing off-target effects. Nanoscale drug carriers can modulate the release kinetics of AEDs, ensuring sustained therapeutic concentrations in the brain. This paper examines responsive neurostimulation (RNS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), highlighting their mechanisms of action. Furthermore, adjunctive therapies, like cannabidiol (CBD) and the ketogenic diet, have further broadened the spectrum of epilepsy management.
The purpose of this study was to examine how adolescents' reports of stressful life events, depressive symptoms, and coping were related with their sexual risk behaviors. This study used data from waves 1 and 2 (ages 13-20 years, N=3,884) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative longitudinal data set of 7th-through 12th-grade students in the US collected between 1994 and 2009. For female participants, reports of stressful life events predicted having a positive history of STIs (aOR = 2.16, 95% CI 1.87-2.50), contraceptive nonuse at last sexual intercourse (aOR = 1.18, 95% CI 1.03-1.34) and frequency of sexual acts (aOR = 1.53, 95% CI 1.39-1.69) after controlling for age, race/ethnicity and socioeconomic status. Additionally, for males, higher levels of stressful life events predicted reporting a history of STI (aOR = 2.01, 95% CI 1.83-2.46), nonuse of contraception (aOR = 1.23, 95% CI 1.07-1.43), and frequency of sexual intercourse (aOR = 1.33, 95% CI 1.23-1.46). Lack of effective coping was related to a greater risk of contraceptive nonuse at last sexual intercourse among females (aOR = 1.08, 95% CI 1.10-1.16) and males (aOR = 1.16, CI 1.06-1.26). Findings indicate that stressful life events are significantly associated with increased sexual risk behaviors in both females and males. Among females, higher reports of stressful life events predicted greater odds of STI history, nonuse of contraceptives, and more frequent sexual activity, even after adjusting for age, race/ethnicity and socioeconomic status. Similarly, males experiencing more stressful events also reported higher rates of STI history, contraceptive nonuse, and sexual activity. Additionally, lack of effective coping skills further heightened the risk of contraceptive nonuse in both groups. These findings suggest that interventions targeting stressful life events should be considered as a component of programs aimed at reducing sexual risk behaviors among adolescents.
Neurotransmitters (dopamine, serotonin, noradrenaline, and acetylcholine) play crucial roles in the regulation of various physiological processes. An imbalance in their levels can result in numerous neurological and psychiatric disorders, such as depression, anxiety, and schizophrenia. Numerous computational approaches enhance the efficiency of drug discovery, one of which is the design of analogs through bioisosteric replacement. Aripiprazole (APZ), a partial agonist of dopamine D2 receptors, is widely used in treating schizophrenia and bipolar disorder. However, prolonged APZ use can lead to side effects such as cardiovascular and liver toxicity. This study aims to in silico design APZ analogs with an improved pharmacological, drug-likeness, and reduced toxicity profile. APZ analogs were generated using the MolOpt tool. Their pharmacokinetic and toxicological (ADMET) profiles were calculated using ADMETLab 3.0 online tool. Drug likeness (DL) and drug score (DS) were predicted using Osiris property explorer (PEO). Molecular docking studies were conducted against the protein (PDB ID: 7DFP) using ArgusLab 4.0.1. A total of 983 APZ analogs were generated and 83 analogs were screened for molecular docking based on ADMET properties, DL, and DS. Docking analysis revealed that key interactions with Asp114 in the target protein were preserved in several bioisosteres, indicating potential pharmacological relevance. Based on ADMET analysis, DL scores, DS, and docking results, the APZ bioisosteres, particularly B104, B170, and C78, emerged as promising candidates for further investigation as potential antipsychotic agents. Further work is in progress in order to evaluate the potential of these analogs as antipsychotic agents.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and motor dysfunction. The monoamine oxidase B (MAOB) pathway plays a critical role in the pathogenesis of PD by contributing to neurodegeneration through oxidative stress. Precision medicine offers a transformative approach to PD treatment by leveraging genetic and molecular insights to tailor therapeutic strategies. This review explores the intersection of precision medicine and antipsychotic drugs in modulating the MAO-B pathway to mitigate PD symptoms. We discuss the biochemistry and function of MAO-B, its impact on disease progression, and the potential of genetic profiling to personalize treatment. Additionally, we examine the role of antipsychotic drugs, their mechanisms of action, and their interactions with the MAO-B pathway. The review highlights personalized approaches to MAO-B inhibition and the clinical evidence supporting these strategies. We address the challenges and limitations in implementing precision medicine, such as technical difficulties, drug interactions, and variability in patient responses. Finally, we explore future directions, including advances in precision medicine technologies and emerging therapies and their potential to enhance PD management. This review examines the indirect interaction between antipsychotics and the MAO-B pathway, highlighting how genetic variations and enzyme activity may influence drug efficacy, safety, and potential adverse effects, particularly when combined with MAO-B inhibitors in neuropsychiatric treatments.
Neuroleptic drug therapy, used to manage psychotic disorders, often induces hormonal disruptions that can impact patient health and treatment outcomes. This review explores the relationship between neuroleptic medications and the endocrine system, highlighting current insights and clinical challenges. Antipsychotic drugs often elevate prolactin levels, leading to hyperprolactinemia, which manifests as galactorrhea, amenorrhea, and sexual dysfunction. These medications can also alter insulin and glucagon levels, contributing to metabolic syndromes, like type 2 diabetes and insulin resistance. Disruption of thyroid hormone homeostasis can result in hypothyroidism or hyperthyroidism, exacerbating psychiatric symptoms. Moreover, neuroleptic drugs affect growth hormone and adrenal function, potentially causing weight gain and adrenal insufficiency. Understanding these hormonal side effects is crucial for developing treatment plans that mitigate adverse effects while optimizing psychiatric care. Despite advances in psychopharmacology, challenges remain in predicting individual patient responses and managing long-term endocrine complications. Current research underscores the need for routine endocrine monitoring in patients on neuroleptic therapy and exploring adjunctive treatments to counteract these side effects. Future studies should focus on elucidating the molecular mechanisms underlying these hormonal disruptions and developing targeted interventions to improve patient outcomes. This review provides an overview of the hormonal side effects of neuroleptic drugs, emphasizing the importance of interdisciplinary approaches in addressing the needs of patients with psychotic disorders.
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, effective treatments remain elusive, highlighting the need for innovative therapeutic approaches. This review article explores enzymatic targets and drug development strategies aimed at combating AD. Key enzymatic targets include beta-secretase (BACE1), gamma-secretase, and tau protein kinases, all of which play critical roles in the pathogenesis of AD. BACE1 and gamma-secretase are involved in the production of amyloid-beta (Aβ) peptides, whose aggregation forms the hallmark amyloid plaques in AD brains. Inhibitors targeting these enzymes aim to reduce Aβ production and accumulation. Tau protein kinases, such as glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinase 5 (CDK5), are implicated in tau hyperphosphorylation and subsequent neurofibrillary tangle formation. Modulating these kinases offers the potential for reducing tau pathology. The review further discusses various drug development strategies, including small-molecule inhibitors, monoclonal antibodies, and gene therapy. Small molecule inhibitors, such as BACE1 and gamma-secretase inhibitors, have shown promise in preclinical studies but face challenges related to specificity and side effects. Monoclonal antibodies targeting Aβ and tau provide an alternative approach, with several candidates currently undergoing clinical trials. Gene therapy represents a cutting-edge strategy aiming to correct or modulate disease-causing genetic mutations. In summary, targeting enzymatic pathways involved in AD pathogenesis offers a promising avenue for drug development. While significant challenges remain, ongoing research and clinical trials continue to advance our understanding and potential treatment options for this debilitating disease.
Abstract: Epilepsy is the second most typical chronic disorder, described by recurrent seizures and uncontrolled electrical signaling from neurons in the cerebral cortex. Stimulated astrocytes, along with microglia, promote cytokines that cause neuroinflammation, leading to a chain reaction of subsequent steps involving neurons as well as endothelial cells along the blood-brain barrier. Inflammation in the brain’s neural network can cause convulsions and epilepsy. The migration of albumin proteins and the infiltration of peripheral immune cells from the serum into the brain disrupt BBB, which, in turn, activates astrocytes and microglia, which stimulate pro-inflammatory mediators like cytokines, chemokines, and other inflammatory mediators. They increase the glutamate level and cause an influx of calcium ions, leading to the production of less GABA and a decrease in the influx of chloride ions. These events exacerbate the inflammatory process that leads to neuronal excitability and contribute further to the development of epilepsy. In this review, we discuss how astrocytes, microglia, and neurons stimulate cytokines, chemokines, and other inflammatory mediators that play an essential role in the development of epilepsy. This review also explore how the permeability of the blood-brain barrier promotes neuroinflammation and contributes to epileptogenesis. The purpose of this review is to present knowledge on neuroinflammation so that new antiepileptic drugs can be developed to prevent this disorder.
Donanemab is the first antibody to target pyroglutamate-modified amyloid-beta in Alzheimer's disease selectively; thus, it represents a significant breakthrough in disease-modifying treatments. Importantly, its mechanism of action encourages adequate clearance of plaques and does not even worsen outcomes for early-stage patients, in contrast to previous treatments that did not promote clearing for plaques or even worsened the outcomes of early-stage patients. The integration of quantum computing in drug discovery holds tremendous transformations in terms of enhancing the therapeutic approach against Alzheimer's disease. Researchers can speed up discovering novel compounds, optimize treatment regimens, and personalize patient care according to individual neurobiological profiles by using quantum computing powers. The letter to the editor discusses the unique attributes of Donanemab, its clinical superiority, and the related side effects, besides pushing for the promising future of integrating quantum computing into the paradigms of Alzheimer's treatment. Though promising, integrating quantum computing into medical practice is challenged by factors such as high computational costs, data privacy, and ethical considerations that must be taken within strict regulatory frameworks.
Parkinson's disease (PD) is a progressive neurological condition characterized by bradykinesia, rigidity, tremors, and impaired balance, among other motor impairments. The issue arises from dopaminergic neurons located in the spinal column of the brain. This research report examines the therapeutic potential of dopaminergic medications in the management of Parkinson's disease. The central concept of Parkinson's disease (PD) revolves around the notion that dopaminergic pathways exert significant influence over the regulation of movement. The book examines various dopaminergic medications, elucidating their mechanisms of action and the impact they exert on dopamine signaling. Examples of these medications include levodopa, dopamine agonists, and monoamine oxidase-B (MAO-B) inhibitors. Although dopaminergic medicines initially aid in the treatment of Parkinson's disease (PD), prolonged usage of these medications gives rise to several complications. Experiencing dyskinesias and motor fluctuations, characterized by episodes of involuntary movements and behaviors that are undesired, is a significant challenge. This study investigates the underlying causes of these difficulties and explores potential treatment options, including the use of controlled-release formulations and further therapy. The book discusses the non-motor symptoms of Parkinson's disease (PD), as well as the use of dopaminergic medications to treat mood disorders, autonomic dysfunction, and cognitive loss. Dopaminergic medications remain crucial in reducing motor symptoms and enhancing the quality of life for those with Parkinson's disease. Parkinson's disease (PD) is a complex condition with multiple distinct variations. In order to address its existing challenges and explore its potential implications for future Parkinson's disease medications, a comprehensive and effectively coordinated strategy is required.
Abstract: Despite the availability of numerous anti-hyperglycemic and psychoactive drugs, and diverse therapeutic modalities, prevention and cure of diabetes-associated mental health problems continue to be a major challenge for medical practitioners. Considerable efforts have been made in many research laboratories, including ours, to identify the bioactive of traditionally known medicinal or food plants to identify their bioactive that could be used for the treatment of diabetes and comorbidities in metabolic disorders. Andrographis paniculata (Burm. F.) Wall. Ex. Nees. has been used in Ayurvedic and other traditionally known healthcare systems of India and many other Asian countries. Due to its extremely bitter taste, it is often referred to as the “king of bitters” and commonly known as “Kalmegh”. Andrographolide is one such metabolite of Andrographis paniculata used in many Asiatic countries for the treatment of diverse age and lifestyle-associated chronic diseases now used for discovering and developing anti-diabetic and other drugs. Available data on andrographolide and Andrographis paniculata strongly recommend that they could be better therapeutic choices for the prevention of diabetes and associated mental health problems than metformin and other pharmacotherapeutics currently commercialized for such purposes. However, the question of whether andrographolide or extracts of the plant enriched in it could be better suited for such purposes remains open. Currently, available quantitative data on their anti-hyperglycemic effects and brain function-modulating effects useful for answering this question are discussed in this report in light of our current knowledge of the role of gut microbiota in regulating glucose homeostasis and mental health. Their potential uses for discovering and developing drugs or phytotherapeutics from them are also pointed out.
Background: Predicting the nocebo response in randomized controlled trials (RCTs) is crucial as it can help minimize its influence and improve the evaluation of the side effects of interventions for ADHD. The aim of this study is to determine the effect of covariates related to study design, intervention, and patients’ characteristics on the nocebo response in patients with Attention Deficit Hyperactivity Disorder (ADHD) using Metaforest, and, ultimately, to investigate Metaforest’s performance in predicting nocebo response in ADHD RCTs. Methods: This study is a secondary analysis of a previously published systematic review [1]. Nocebo response was defined as the proportion of patients experiencing at least one AE while receiving a placebo. We used Metaforest for investigating patient-, intervention, and study design-related nocebo response moderators in ADHD RCTs. Results: One hundred and five studies were included. Overall, 55.4% of patients experienced at least one AE while receiving placebo. However, between-study variability on nocebo response was very high, with nocebo response ranging from 4.2% to 90.2%, leading to high statistical heterogeneity (I2 = 88.3%). Older patients showed a higher nocebo response. The moderating effects of the year of publication, treatment length and gender were also significant. The predictive performance of the model was low-moderate (R2 test = 0, 1922; MSE = 0, 0408). Conclusion: Age was the most important nocebo response modifier, followed by year of publication, treatment length and gender. Metaforest lacked the capability to predict nocebo responses in future studies.
Abstract: Alzheimer's disease is distinguished by gradual changes in behavior because of the aggregation of β-amyloid and τ protein that blocks the signal transduction pathway. It is one of the major problems in the current scenario. It mainly occurs after the age of 60 and eventually leads to memory loss. Nonetheless, medicinal plants have therapeutic potential to improve many diseases. Medicinal drugs with their phytoconstituents may offer therapeutic potential for improving the preventive treatment for Alzheimer's disease. Five synthetic drugs that have been approved by the FDA include Tacrine, Rivastigmine, Donepezil, Galantamine, and Memantine for the symptomatic treatment of Alzheimer's. In the search for effective anti-Alzheimer's drugs from a natural source, we discovered marine resources as the origin of the therapeutic and nutritional compound. The methodology involves conducting a comprehensive literature survey. The database search methodology used in this review was the use of keywords, which can be found in the article pertaining to Alzheimer’s disease. The significant articles focused on marine flora phytoconstituents, such as Acetylcholinesterase or butyrylcholinesterase inhibitors, thus prompting a comprehensive review based on pertinent information. The review included descriptions of various studies, revealing that numerous compounds derived from marine sources have demonstrated promising efficacy in the treatment of Alzheimer's disease. Many compounds that originated from marine sources showed good efficacy in treating Alzheimer’s disease. Acetylcholinesterase or butyrylcholinesterase inhibition was the main pharmacological mechanism that was reported for most of the molecules, however, few articles having alternative anti Alzheimer’s mechanisms have also been reported. This article highlights marine compounds derived from marine sources like algae, fungi, and sponges, which can combat Alzheimer's disease.
