{"title":"Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease.","authors":"Caroline Coppinger, Briana Pomales, Mohammad Reza Movahed, Meredith Marefat, Mehrnoosh Hashemzadeh","doi":"10.2174/0127724328250471231222094648","DOIUrl":"10.2174/0127724328250471231222094648","url":null,"abstract":"<p><p>Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"312-326"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742183","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}
Diptimayee Das, Kanchan M, Abhijit Mitra, Mohamed Y Zaky, Surajit Pathak, Antara Banerjee
{"title":"A Review on the Efficacy of Plant-derived Bio-active Compounds Curcumin and Aged Garlic Extract in Modulating Cancer and Age-related Diseases.","authors":"Diptimayee Das, Kanchan M, Abhijit Mitra, Mohamed Y Zaky, Surajit Pathak, Antara Banerjee","doi":"10.2174/2772432819666230504093227","DOIUrl":"10.2174/2772432819666230504093227","url":null,"abstract":"<p><p>Aging is a process characterized by accumulating degenerative changes resulting in the death of an organism. Aging is mediated by various pathways that are directly linked to the individual's lifespan and are shunted for many age-related diseases. Many strategies for alleviating age-related diseases have been studied, which can target cells and molecules. Modern drugs such as Metformin, Rapamycin, and other drugs are used to reduce the effects of age-related diseases. Despite their beneficial activity, they possess some side effects which can limit their applications, mainly in older adults. Natural phytochemicals which have anti-aging activities have been studied by many researchers from a broader aspect and suggested that plant-based compounds can be a possible, direct, and practical way to treat age-related diseases which has enormous anti-aging activity. Also, studies indicated that the synergistic action of phytochemicals might enhance the biological effect rather than the individual or summative effects of natural compounds. Curcumin has an antioxidant property and is an effective scavenger of reactive oxygen species. Curcumin also has a beneficial role in many age-related diseases like diabetes, cardiovascular disease, neurological disorder, and cancer. Aged garlic extracts are also another bioactive component that has high antioxidant properties. Many studies demonstrated aged garlic extract, which has high antioxidant properties, could play a significant role in anti-aging and age-related diseases. The synergistic effect of these compounds can decrease the requirement of doses of a single drug, thus reducing its side effects caused by increased concentration of the single drug.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"146-162"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828146","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}
Vinod Solipuram, Ramin Soltani, B P Venkatesulu, Saketh Annam, Firoozeh Alavian, Sorayya Ghasemi
{"title":"Efficacy of Anti-VEGF Drugs Based Combination Therapies in Recurrent Glioblastoma: Systematic Review and Meta-Analysis.","authors":"Vinod Solipuram, Ramin Soltani, B P Venkatesulu, Saketh Annam, Firoozeh Alavian, Sorayya Ghasemi","doi":"10.2174/2772432817666220517163609","DOIUrl":"10.2174/2772432817666220517163609","url":null,"abstract":"<p><strong>Background: </strong>Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results.</p><p><strong>Methods: </strong>A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method.</p><p><strong>Results: </strong>Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I<sup>2</sup>=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I<sup>2</sup>=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I<sup>2</sup>=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I<sup>2</sup>=47%) were seen in the combination therapy when compared to the control group.</p><p><strong>Conclusion: </strong>Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"1 1","pages":"173-183"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43898337","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 Therapeutic and Pharmacological Properties of Resveratrol as a Nutraceutical Antioxidant Polyphenol in Health Promotion and Disease Prevention.","authors":"Shiva Mohammadi, Maryam Dalaei Moghadam, Maryam Nasiriasl, Morteza Akhzari, Mahdi Barazesh","doi":"10.2174/0127724328268507231218051058","DOIUrl":"10.2174/0127724328268507231218051058","url":null,"abstract":"<p><p>Resveratrol (3, 5, 4'-trihydroxystilbene) is a polyphenolic derivative with herbal origin. It has attracted considerable attention in recent decades. Many studies have revealed the benefits of Resveratrol over several human disease models, including heart and neurological diseases, nephroprotective, immune regulation, antidiabetic, anti-obesity, age-related diseases, antiviral, and anticancer in experimental and clinical conditions. Recently, the antioxidant and anti-inflammatory activities of Resveratrol have been observed, and it has been shown that Resveratrol reduces inflammatory biomarkers, such as tissue degradation factor, cyclooxygenase 2, nitric oxide synthase, and interleukins. All of these activities appear to be dependent on its structural properties, such as the number and position of the hydroxyl group, which regulates oxidative stress, cell death, and inflammation. Resveratrol is well tolerated and safe even at higher pharmacological doses and desirably affects cardiovascular, neurological, and diabetic diseases. Consequently, it is plausible that Resveratrol can be regarded as a beneficial nutritional additive and a complementary drug, particularly for therapeutic applications. The present review provides an overview of currently available investigations on preventive and therapeutic characteristics and the main molecular mechanisms of Resveratrol and its potent derivatives in various diseases. Thus, this review would enhance knowledge and information about Resveratrol and encourage researchers worldwide to consider it as a pharmaceutical drug to struggle with future health crises against different human disorders.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"327-354"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404648","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}
Mohammad Aadil Bhat, Iqra Usman, Suneela Dhaneshwar
{"title":"Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease.","authors":"Mohammad Aadil Bhat, Iqra Usman, Suneela Dhaneshwar","doi":"10.2174/0127724328245156231008154045","DOIUrl":"10.2174/0127724328245156231008154045","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"234-249"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683029","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":"Meet the Regional Editor","authors":"Jorge Duconge","doi":"10.2174/277243281803230127142803","DOIUrl":"https://doi.org/10.2174/277243281803230127142803","url":null,"abstract":"","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"66 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102906","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":"Acknowledgement to Reviewers","authors":"","doi":"10.2174/277243281803230127151520","DOIUrl":"https://doi.org/10.2174/277243281803230127151520","url":null,"abstract":"","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"66 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136103091","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":"A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor","authors":"Anila Kutty Narayanan, Sudhindran Surendran, Dinesh Balakrishnan, Unnikrishnan Gopalakrishnan, Shweta Malick, Arun Valsan, Abby Cyriac Philips, Christopher J Watson","doi":"10.2174/0127724328239536230919070001","DOIUrl":"https://doi.org/10.2174/0127724328239536230919070001","url":null,"abstract":"Abstract: Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late ’90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"469 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135546437","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":"Meet the Editorial Board Member","authors":"Karel Allegaert","doi":"10.2174/277243281802221128101243","DOIUrl":"https://doi.org/10.2174/277243281802221128101243","url":null,"abstract":"","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136261114","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":"In vitro and In vivo Models used for Drug discovery and Drug screening on Atherosclerotic Research: a Review","authors":"R. J. Rani, S. Sabarinathan, Revathy L R","doi":"10.2174/2772432818666230308092141","DOIUrl":"https://doi.org/10.2174/2772432818666230308092141","url":null,"abstract":"The processes behind atherosclerosis, the largest cause of mortality globally, are largely unknown. Nonetheless, several in vitro and in vivo models have considerably enhanced our insight into the processes behind atherosclerosis and enabled the assessment of potential treatment interventions. This article will examine the in vivo and in vitro models used to investigate atherosclerosis. High Cholesterol feed (HCF) conception and mechanical endothelial dysfunctions are the main characteristics found in the majority of atherosclerosis models. Despite the lack of a single in vivo model that completely replicates the progression of atherosclerosis in humans, there are several promising animal models. In addition, with the arrival of gene-modified animals, these models considerably broaden our understanding of the progression of atherosclerosis.","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"1 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41808684","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}