Current Reviews in Clinical and Experimental Pharmacology最新文献

{"title":"Acetylcholine and Depression: Scrutinizing Future Therapeutic Targets for Novel Drug Development.","authors":"Arzoo Pannu, Ramesh K Goyal","doi":"10.2174/0127724328311930240907133618","DOIUrl":"10.2174/0127724328311930240907133618","url":null,"abstract":"<p><p>Depression, a pervasive and disabling mental health disorder, presents a global healthcare challenge. Despite persistent research on its etiology and pathophysiology, many aspects remain unclear. Predominant neurobiological research and traditional pharmacotherapies have pointed out the monoamine hypothesis as a pivotal factor in the pathophysiology of depression. However, emerging perspectives on the monoamine hypothesis highlight the significance of the cholinergic system, a major regulator of diverse CNS functions encompassing attention, arousal, cognition, and memory. Cognitive impairments were frequently observed in depression along with other symptoms i.e. low mood and anhedonia. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Web of Science) from their inception until May 2023. We screened 1,200 articles, of which 400 full-text articles were assessed for eligibility, and 231 studies met the inclusion criteria. The review included both pre-clinical and clinical studies focusing on the role of acetylcholine (ACh) and its receptors in depression. Data extraction and quality assessment were performed independently by two reviewers. In literature, both pre-clinical and clinical studies suggest that elevated central ACh levels may contribute to depression, prompting investigations into intervention strategies targeting mAChRs/nAChRs and AChE. These receptors have become a critical target in drug-design strategies aimed at addressing depression-like symptoms. In addition, research has demonstrated a significant antidepressant-like effect of AChEIs in a dose-dependent manner in animal models. Hence, this evidence over the past decades underscores the pivotal role of the cholinergic system in mood regulation, offering promise for novel depression treatments. In this review, we tried to summarize the historical evolution of the cholinergic system from early discoveries to its role in the pathophysiology of depression. It presents evidence for the involvement of mAChRs and nAChRs, as well as AChE, in depression. By outlining the cholinergic theory of depression, this review suggests a novel therapeutic approach, emphasizing the role of ACh in the complex depression pathophysiology, and presenting avenues for further research and the development of targeted interventions.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"20 3","pages":"180-204"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antioxidant Properties and Cardiovascular, Antidiabetic, and Renal Effects of Trimetazidine Described in Research on Experimental Models.","authors":"Aldahir Mero Rios, Juan Antonio Moran Pinzon, Ciara Ordonez, Estela Guerrero de Leon","doi":"10.2174/0127724328303999240607072031","DOIUrl":"10.2174/0127724328303999240607072031","url":null,"abstract":"<p><p>Experimental studies have played an essential role in drug identification and development in biomedical research. These studies also have applications in conducting postmarketing evaluations to elucidate the mechanisms responsible for their actions. Preclinical studies on marketed drugs have led to the discovery of new mechanisms or biological effects, opening the possibility of expanding their therapeutic applications. Since its discovery, trimetazidine has been used as an antianginal drug. However, after its commercialization, the molecular actions and impact of this drug on ischemic and non-ischemic pathologies have become known. This article presents the mechanisms and antioxidant actions of trimetazidine associated with the effects observed in experimental models of heart disease, nephropathy, and diabetes mellitus. A non-systematic search of the PubMed database was performed using terms related to our objectives. We selected articles on studies focused on cardioprotection, nephroprotection, antioxidants, or diabetic heart disease, which were carried out in preclinical experimental models. The information compiled in this review shows that trimetazidine is effective in reducing damage associated with oxidative stress, as evaluated in different experimental models. The cardioprotective and nephroprotective effects of this drug have been demonstrated in ischemic and non-ischemic models.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"20 3","pages":"169-178"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.","authors":"Mengxia Wang, Yan Ma, Bao Zeng, Wenhao Yang, Cuihong Huang, Benqin Tang","doi":"10.2174/0127724328335219241202142003","DOIUrl":"10.2174/0127724328335219241202142003","url":null,"abstract":"<p><p>The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"334-348"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of Indian Spices in the Management of Diabetic Complication: A Pre-Clinical and Clinical Review.","authors":"Swarnalata Mohapatra, Santosh Ranjit, Gurudutta Pattnaik, Patitapabana Parida, Sonali Dutta, Goutam Ghosh, Goutam Rath, Biswakanth Kar","doi":"10.2174/0127724328331153240918093157","DOIUrl":"10.2174/0127724328331153240918093157","url":null,"abstract":"<p><p>Diabetic is a metabolic disorder that is concerning for people worldwide, caused by a lack of insulin or ineffective production of insulin in the pancreas. Diabetic retinopathy, nephropathy, and neuropathy are significant microvascular complications of diabetes mellitus, contributing to substantial morbidity and mortality worldwide. Several synthetic medications have been developed. However, none of the compounds provides complete recovery. Long-term use of some synthetic medications might have serious negative effects, thus, there is a need for safe, affordable, and effective medications. Throughout human history, traditional ailments have been much respected as a source of treatment. Their widespread usage across the globe suggests that herbs/ spices are becoming an increasingly important component of cutting-edge, contemporary medications. Therefore, the objective of this review is mainly based on the beneficial effect of Indian spices in managing diabetes. We review the current primary and clinical evidence about the potential of Indian spices, including curcumin, ginger, coriander, cumin seed, garlic, clove, cinnamon, curry leaves, and fenugreek seed with mainly their hypoglycemic and antioxidant properties, for treating diabetes mellitus, also managing diabetic-associated complications, such as neuropathy, retinopathy, and nephropathy. Here, we present the pre-clinical and clinical studies demonstrating how these spices can improve glucose metabolism, enhance insulin secretion, and mitigate oxidative stress, potentially alleviating diabetic complications.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"20 2","pages":"140-157"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Tolerability of Various 5-Fluorouracil Formulations as Adjuvant Therapies for Vitiligo Management: A Systematic Review and Meta-Analysis.","authors":"Neveen A Kohaf, Sameh M Sarsik, Samar Salman, Omnya M Amin","doi":"10.2174/0127724328324817241002112025","DOIUrl":"10.2174/0127724328324817241002112025","url":null,"abstract":"<p><strong>Background: </strong>All vitiligo treatments are restricted, and no known treatment reliably produces repigmentation. In this study, we investigated the efficacy and safety of 5-Fluorouracil (5FU) as adjuvant therapy in treating vitiligo.</p><p><strong>Methods: </strong>Using five significant databases, an electronic systematic search of the literature was conducted. Randomized Clinical Trials (RCTs) that investigated 5FU for treating vitiligo in humans were selected for a meta-analysis and systematic review. This study was conducted by following PROSPERO (CRD42022345736).</p><p><strong>Results: </strong>A total of 10 studies involving 302 patients were included in our systematic review. The meta-analysis of eight studies revealed that the combination of 5FU with microneedling showed a statistically significant superior effect in comparison with other treatment modalities in ing >75% repigmentation (OR= 4.47; 95%CI= (2.39, 8.35), P < 0.00001). 5FU with microneedling versus microneedling alone showed higher efficacy of 5FU with statistically significant results (OR= 4.22; 95%CI= (1.55, 11.44), P= 0.005). Regarding the influence of different formulations of 5FU, the meta-regression revealed that the highest efficacy was achieved when microneedling was combined with liposomal formulations. There were not any reported severe side effects related to 5FU.</p><p><strong>Conclusion: </strong>5FU as an adjuvant treatment for vitiligo was found to be more effective in achieving ≥75% repigmentation rates.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"244-258"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation.","authors":"Jiaqi Yu, Yuanfeng Fu, Weifeng Xu, Ren-Bo Ding, Jiaolin Bao","doi":"10.2174/0127724328314214240829181006","DOIUrl":"10.2174/0127724328314214240829181006","url":null,"abstract":"<p><p>Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"98-102"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Deutetrabenazine in the Treatment of Chorea Linked with Huntington's Disease.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0127724328312991241001051813","DOIUrl":"10.2174/0127724328312991241001051813","url":null,"abstract":"<p><p>This review investigates the efficacy of deutetrabenazine in the management of chorea related to HD. Motor, psychological, and cognitive symptoms characterize HD, a neurodegenerative disease. One prominent movement disorder associated with HD is chorea, which results in uncontrollably jerky movements of the muscles. HD has no known cure; instead, symptom management with a variety of medication options is the main goal. Effective management is essential because chorea has a significant impact on patients' quality of life. Dutetrabenazine is the first deuterated medication to receive approval from the US Food and Drug Administration (FDA) for the therapeutic treatment of chorea in Huntington's disease (HD). Treating chorea associated with HD may benefit from the use of deutetrabenazine. The novel compound deutetrabenazine contains deuterium. It inhibits CYP2D6 metabolism, prolongs the half-lives of active metabolites, and may cause persistent systemic exposure while maintaining significant pharmacological action. Deutetrabenazine decreases the release of monoamines, including dopamine, in the synaptic cleft by inhibiting the VMAT2 vesicular monoamine transporter. For chorea, this mechanism has a therapeutic effect. For the treatment of choreiform movement and tardive dyskinesia in HD, the FDA approved deutetrabenazine in 2017. Here we highlight, Deutetrabenazine as a promising new treatment for Huntington's disease chorea, for patients with chorea, deutetrabenazine offers hope for an enhanced quality of life. To completely understand its effectiveness and potential advantages, additional research is necessary, including direct comparison studies, as a result of the mixed study results.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"269-288"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Metformin in Modifying Ferroptosis to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: A Narrative Review.","authors":"Mohammadjavad Sotoudeheian, Reza Azarbad, Seyed-Mohamad-Sadegh Mirahmadi, Navid N","doi":"10.2174/0127724328328193241029103831","DOIUrl":"10.2174/0127724328328193241029103831","url":null,"abstract":"<p><p>Fatty liver disease (FLD) is a well-known metabolic disorder associated with hepatic steatosis and tissue lipid accumulation. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent and challenging condition that is linked to obesity, diabetes, and other metabolic disorders. MAFLD, previously called NAFLD or nonalcoholic fatty liver disease, is associated with pathological changes in liver tissue. In recent decades, there has been a growing interest in the potential of metformin, a commonly used medication for type-2 diabetes, to help treat MAFLD. Metformin has shown promising potential in treating MAFLD through its ability to modify ferroptosis, a novel form of programmed cell death. In this critical review, we explain the current knowledge about MAFLD, the potential role of ferroptosis in its pathogenesis, and the mechanisms by which metformin may modulate ferroptosis in the context of MAFLD. Additionally, evidence supporting the usage of metformin in treating MAFLD is explained. Overall, this review explains the potential of metformin as a novel therapeutic approach for MAFLD by targeting ferroptosis and provides valuable insights for future research in this area.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"301-321"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances.","authors":"Mudasir Maqbool Bhat, Md Sadique Hussain, Ajay Singh Bisht, Mohit Agrawal, Ayesha Sultana, Navneet Khurana, Rajesh Kumar","doi":"10.2174/0127724328325178241210174545","DOIUrl":"10.2174/0127724328325178241210174545","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"289-300"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Pharmacotherapeutic Strategies Using Bigel Drug Delivery Systems.","authors":"Ali H Eid","doi":"10.2174/277243282003250219232030","DOIUrl":"https://doi.org/10.2174/277243282003250219232030","url":null,"abstract":"","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"20 3","pages":"243"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}