Current pharmaceutical design最新文献

{"title":"Cholesterol-Lowering Effects of BMS-303141 Analogues via Inhibition of Adenosine Triphosphate-Citrate Lyase.","authors":"In-Gyu Je, Joon-Tae Park, Hyeong Jun Lee, A-Rang Im, Jaecheol Lee, Ki-Young Kim","doi":"10.2174/0113816128387531250713164724","DOIUrl":"https://doi.org/10.2174/0113816128387531250713164724","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol is considered a major factor contributing to cardiovascular diseases. Statins, the most commonly prescribed cholesterol-lowering drugs, are known to have various limitations. Inhibition of Adenosine Triphosphate-Citrate Lyase (ACLY) has been proposed as an alternative therapeutic strategy for managing hypercholesterolemia by lowering cholesterol levels. This has led to the discovery of a cell-permeable small molecule ACLY inhibitor.</p><p><strong>Methods: </strong>ACLY enzyme activity was assessed using an ACLY Assay Kit with the ADP-Glo Kinase Assay Kit. HepG2 cells were treated with test compounds to demonstrate cholesterol and fatty acid synthesis. Pharmacokinetic studies were performed on CD-1 mice following a single oral dose of the compounds. Hypercholesterolemia was induced in mice through a High-Fat and High Cholesterol Diet (HFHCD), and drugs were administered orally for six weeks. Serum and hepatic lipid profiles were subsequently analyzed.</p><p><strong>Results: </strong>To increase the pharmacochemical properties, four analogues of BMS-303141, ID0018, ID0023, ID0085, and ID0106, were designed and synthesized. These compounds showed superior ACLY inhibitory activity and dose-dependent suppression of cholesterol and fatty acid synthesis in HepG2 cells. Among the analogues, ID0085 exhibited the most potent ACLY inhibition (IC50: 45 nM, 10-fold lower than BMS- 303141) and achieved near-complete suppression in cholesterol and fatty acid synthesis at the highest concentration. Pharmacokinetic studies revealed improved half-lives and systemic exposures for all analogues. In hypercholesterolemic mouse models, test compounds significantly reduced serum total cholesterol (32.0-57.3%) and low-density lipoprotein cholesterol (67.5-80.2%) levels compared to the vehicle group. Notably, ID0085 also increased high-density lipoprotein cholesterol levels.</p><p><strong>Conclusion: </strong>Based on the results, ID0085 appears to be the most promising therapeutic candidate for the treatment of hypercholesterolemia.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF21 Analogues and MASLD: A Summary of Preclinical and Clinical Data.","authors":"Chrysoula Boutari, Achilleas Triantafyllou, Lavrentis Papalavrentios, Ioannis Goulis, Emmanouil Sinakos","doi":"10.2174/0113816128374854250709050425","DOIUrl":"https://doi.org/10.2174/0113816128374854250709050425","url":null,"abstract":"<p><p>Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most frequent chronic liver disease, which is closely associated with metabolic syndrome and obesity. Although it has now reached epidemic proportions, the treatment of this disease remains a challenge. Currently, there is only one drug approved for metabolic dysfunction-associated steatohepatitis (MASH), and various pharmaceutical agents have reached phase 3 of clinical trials and appear as potential drugs for the disease. Fibroblast Growth Factor (FGF) 21 has been gaining increasing interest as a possible therapeutic target for MASLD. FGF21 analogues, with an improved pharmacodynamic and pharmacokinetic profile, exert pleiotropic, favorable effects on liver function and histology, as well as systemic metabolism. They also appear to be effective in alleviating hepatic steatosis, steatohepatitis, and fibrosis in MASH. Among various others, efruxifermin, pegozafermin, pegbelfermin, and BOS-580 are FGF-21 analogues that have resulted in significant improvements in liver fat, fibrosis, and measures of liver function in the context of phase 2 clinical trials. This review summarizes the preclinical and clinical data from FGF21 analogues for MASLD and MASH.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Multifaceted Potential of Natural Flavonoid Diosmetin in Human Diseases.","authors":"Dhirendra Singh, Randhir Singh, Inderjeet Verma","doi":"10.2174/0113816128375348250709222244","DOIUrl":"https://doi.org/10.2174/0113816128375348250709222244","url":null,"abstract":"<p><p>Flavonoids are secondary metabolites that are closely related to polyphenols and have a diverse structure. These are present in the form of aglycones or glycosides in many fruits and vegetables. Diosmetin (DIO) is a bioactive flavonoid primarily found in the olive tree (Olea europaea L) and has been recognised for its diverse therapeutic potential in the management of many illnesses. In recent years, multiple pharmacological properties of DIO have been shown, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, hepatoprotective, renal protective, lung protective, retinal protective, neuroprotective and anticancer activity. Therefore, considering the pharmacological potential of DIO, the present work was designed to further explore its pharmacological actions in the treatment of various diseases.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme.","authors":"Pankaj Arora, Riya, Viney Chawla, Pooja A Chawla, Richu Singla, Honey Goel","doi":"10.2174/0113816128373247250529114324","DOIUrl":"https://doi.org/10.2174/0113816128373247250529114324","url":null,"abstract":"<p><p>The quintessential hallmarks of brain malignancies hinge on their acquired biological traits, which encompass mutations in the epidermal growth factor receptor (EGFR), as well as vasculogenesis and cellular energy reprogramming. Glioblastoma multiforme (GBM) remains a prominent malignant form of brain tumor in humans. GBM patients exhibit a dismal prognosis with a median survival time of only 1-2 years due to the complex pathophysiology, the development of resistance by cancer cells, and the inability of therapeutic components to pass the blood-brain barrier (BBB) and blood-tumor barrier (BTB). BBB, a network of endothelial cells surrounded by astrocyte foot processes, primarily circumvents the transit of therapeutic biomacromolecules and drugs. To address those challenges, targeted therapies to the nose via brain drug delivery have emerged as a steadfast framework for mitigating neurological disorders, bypassing the BBB. A myriad of preclinical paradigms based on intranasal drug approaches utilizing conventional drug therapeutics have been designed and tested for delivering both liquid and solid particle formulations that effectively encapsulate therapeutic biomolecules in brain tissues, especially in GBM. However, there are significant gaps in the effective translation of nose-to-brain delivery approaches for achieving higher drug concentrations of anticancer drugs at the targeted regions in pathological states, such as GBM, without causing damage to healthy tissues. Therefore, the current body of literature aims to corroborate the mechanistic understanding in non-invasive designs using intranasal therapies that efficiently penetrate the BBB and circumvent systemic adverse effects while treating GBM.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgolide as a Promising Multi-Target Therapeutic for Alzheimer's Disease: Targeting ApoE4 and Beyond.","authors":"Saba Beigh, Mansoor Alsahag, Ali Alisaac, Sajad Ahmad Dar, Mohammad H Alyami, Soma E Ajlan, Hesham A Malak, Abdullateef Abdullah Alshehri","doi":"10.2174/0113816128386836250723134001","DOIUrl":"https://doi.org/10.2174/0113816128386836250723134001","url":null,"abstract":"<p><strong>Introduction: </strong>The progressive neurodegenerative disease known as Alzheimer's disease (AD) is typified by neuroinflammation, amyloid-beta buildup, and cognitive impairment. Current pharmacological treatments merely alleviate symptoms, despite extensive research, which underscores the need for innovative, multi-target medicines. Since apolipoprotein E4 (ApoE4) is a significant genetic risk factor linked to the development of AD, it is a potentially effective treatment target. With their neuroprotective qualities, natural substances like ginkgolide may help treat some diseases. This study investigates ginkgolide's potential as a multi-target treatment for AD, with a particular emphasis on how it interacts with the ApoE4 N-terminal domain.</p><p><strong>Methods: </strong>The interaction between Ginkgolide and ApoE4 (PDB ID: 8AX8) was assessed using pharmacokinetic profiling, molecular docking, and molecular dynamics (MD) simulations. MD simulations were used to determine stability, and AutoDock Vina was used to obtain the binding affinity. To predict pharmacokinetics and toxicity, SwissADME and PkCSM were employed. The effectiveness of ginkgolide was contextualized using comparative docking with curcumin and resveratrol.</p><p><strong>Results: </strong>Ginkgolide formed sustained hydrophobic contacts with important sites and demonstrated a substantial binding affinity (-7.1 kcal/mol) to ApoE4. MD simulations verified negligible fluctuations and complex stability over 100 ns. Pharmacokinetics showed no significant toxicity risks, good gastrointestinal absorption, and favorable blood-brain barrier permeability. In terms of binding affinity and stability, ginkgolide fared better than curcumin and resveratrol, indicating its greater therapeutic potential.</p><p><strong>Discussion: </strong>The results indicate that ginkgolide effectively binds and stabilizes the ApoE4 N-terminal domain, supporting its potential role in modulating a key pathological factor in Alzheimer's disease. Its superior pharmacokinetic profile and interaction dynamics compared to curcumin and resveratrol suggest a broader therapeutic relevance. These in silico insights provide a mechanistic basis for further investigation into ginkgolide's neuroprotective effects.</p><p><strong>Conclusion: </strong>The results demonstrated ginkgolide as a potentially effective multi-target treatment for AD through ApoE4 regulation. It is a better option than other natural chemicals because of its potent binding affinity, stability, and pharmacokinetics. These findings highlight the value of in silico methods in the early stages of drug discovery and the need for additional experimental support before they can be used in clinical settings.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Astragalus Membranaceus for Oral Submucosal Fibrosis: A Network Pharmacology and Experimental Approach.","authors":"Fang Zhang, Yonglian Wu, Chen Cheng, YaHsin Cheng, Ruifang Gao","doi":"10.2174/0113816128374420250707120128","DOIUrl":"https://doi.org/10.2174/0113816128374420250707120128","url":null,"abstract":"<p><strong>Background: </strong>Oral Submucosal Fibrosis (OSF) is a chronic progressive oral mucosal disease with a tendency to progress to cancer. Astragalus membranaceus (AST) is a traditional Chinese medicine used to invigorate Qi and strengthen the body, with anti-fibrosis properties. However, the effect and mechanism of AST on OSF remain unclear.</p><p><strong>Objective: </strong>This study aims to explore the mechanism of Astragalus membranaceus in OSF using network pharmacology and to validate its effects on oral mucosal fibroblasts through in-vitro experiments.</p><p><strong>Methods: </strong>Network pharmacology was employed to construct an \"AST - ingredient - target - OSF\" network and perform Protein-Protein Interaction (PPI) analysis. Molecular docking was used to confirm core interactions between key targets and ingredients, and all results met the criterion of a binding energy of <- -1.2 kcal/mol. In-vitro experiments were conducted to assess the cytotoxicity of arecoline (ARE) and Astragalus membranaceus injection (ASI) on Oral Mucosal Fibroblasts (OMF).</p><p><strong>Results: </strong>Analysis revealed 68 common targets between AST and OSF, and a corresponding PPI network was constructed. KEGG and GO enrichment analyses identified 138 pathways and 178 biological processes associated with these targets. Molecular docking confirmed core interactions between five key targets (EGFR, VEGFA, MAPK3, HRAS, JUN) and other ingredients. In-vitro experiments showed that ARE at concentrations of 20-40 μg/ml significantly upregulated ACTA2, EGFR, and VEGFA mRNA expression. ASI treatment at varying concentrations significantly inhibited these increases, with 100 mg/ml ASI downregulating EGFR and VEGFA mRNA, and 300-400 mg/ml ASI reducing ACTA2 expression.</p><p><strong>Conclusion: </strong>Astragalus membranaceus injection may suppress ARE-induced fibrosis by targeting EGFR and VEGFA, supporting its potential therapeutic role in the treatment of OSF.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragalus-Safflower Combination Promotes Vascular Neogenesis in a Rat Model of Ischemic Stroke via Inhibition of MAPK/NF-κB and Activation of VEGF/Notch1 Pathways.","authors":"Fuyu Liu, Mimi Wang, Yonggang Feng, Kaixin Shan, Yun Han, Xiang Meng, Suxiang Feng, Mingsan Miao, Yucheng Li, Xiaoyan Fang","doi":"10.2174/0113816128381137250716212446","DOIUrl":"https://doi.org/10.2174/0113816128381137250716212446","url":null,"abstract":"<p><strong>Introduction: </strong>The combination of Astragalus membranaceus and Safflower (AS) is known for its efficacy in benefiting Qi and activating blood circulation, making it a frequently used empirical combination in traditional Chinese medicine. Numerous reports have highlighted the interventional effect of this combination in treating ischemic stroke (IS). However, the active ingredients and potential mechanisms underlying its treatment of stroke have not been fully elucidated.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/ MS), along with various data processing methods, were utilized to identify and assess the chemical constituents in rat serum following AS gavage administration. Chemical constituent targets were predicted using the SEA and Swiss Target Prediction databases, while IS-related targets were sourced from the GeneCards, OMIM, and TTD databases. The intersecting targets of constituents and diseases were screened, and a core target network map was constructed using the String database and Cytoscape software. KEGG pathway enrichment of core targets was analyzed using DAVID and Metascape databases. The middle cerebral artery occlusion (MCAO) rat model was established to evaluate the cerebroprotective effects of AS. The accuracy of predicted pathways was validated using immunofluorescence (IF) and Western blot (WB) analyses.</p><p><strong>Results: </strong>Thirty-five ingredients in serum were identified, and 437 targets and 3748 IS-related targets were identified, 291 of which overlapped. Protein-protein interaction (PPI) analysis predicted 15 major targets, including TNF and MAPK3. KEGG pathway analysis indicated that the MAPK/NF-κB and VEGF/Notch1 signaling pathways may play pivotal roles in the therapeutic effects of AS in IS. Moreover, AS significantly ameliorated neurological and motor function impairments, as well as brain histopathological damage, in MCAO rats. AS treatment led to reduced levels of the inflammatory cytokines IL-6 and TNF-α, inhibited astrocyte hyperactivation, decreased nuclear translocation of NF-κB p65, reduced expression of p-MAPK (Erk1/2)/ MAPK (Erk1/2) and p-NF-κB (p65)/NF-κB (p65) proteins, increased the number of CD31+/Ki67+ and VEGF+/ Ki67+-positive vessels, and upregulated the expression of VEGF, VEGFR-2, Notch1, and DLL4 proteins.</p><p><strong>Conclusion: </strong>AS may regulate MAPK/NF-κB and VEGF/Notch1 pathways to reduce inflammation and promote post-ischemic neovascularization, providing a promising method for the treatment of ischemic stroke.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy for the Treatment of Osteoarthritis: Advances and Prospective.","authors":"Anjali Rana, Rishabha Malviya, Shivam Rajput, Sathvik Belagodu Sridhar, Javedh Shareef","doi":"10.2174/0113816128384412250709130211","DOIUrl":"https://doi.org/10.2174/0113816128384412250709130211","url":null,"abstract":"<p><p>Osteoarthritis affects some joints in the body, including the hand's distal interphalangeal joints, knees, and hips. The complex disease known as degenerative osteoarthritis affects every joint in the body. Due to its limited influence on weight-bearing joints and absence of substantial extra-articular symptoms, osteoarthritis is well-suited for targeted gene therapy within the affected joints. The article discusses the field's history, the genes utilised, the techniques of gene delivery (direct vs. indirect), and the most prevalent expression vectors (viral vs. non-viral). A comprehensive literature review was conducted using reputable databases, including Scopus, ScienceDirect, PubMed, and Google Scholar. The study focused on research published over the past decade to ensure the inclusion of recent advancements. This article explores a range of gene therapy strategies developed for the treatment of osteoarthritis. Emphasis was placed on identifying innovative and clinically relevant approaches that have emerged in recent years. By reviewing the most current data, this work aims to provide a detailed overview of the evolving landscape of gene therapy as a potential therapeutic avenue for managing and possibly reversing osteoarthritis symptoms and progression. The goal of gene therapy for osteoarthritis (OA) is to repair damaged cartilage by introducing gene-based therapeutic agents to the affected area in a regulated, site-specific, long-term manner. The synovium and cartilage are two possible intra- articular sites for gene transfer. The most advanced gene therapy method for osteoarthritis is the local gene transfer to synovium technique. IL-1 is a key modulator of cartilage loss in OA, and IL-1 receptor antagonist (IL-1Ra) gene transfer is effective in treating OA in three animal models.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin and Citreorosein from Halodule uninervis Leaf Show the Best Binding Against Breast Cancer Targets AKT1, EGFR, and ESR1.","authors":"Tapas Ranjan Samala, Priyankar Sen","doi":"10.2174/0113816128408970250717095140","DOIUrl":"https://doi.org/10.2174/0113816128408970250717095140","url":null,"abstract":"<p><strong>Introduction: </strong>The marine ecosystem, known for its diverse biochemistry and organisms adapted to harsh environments, contains numerous plants with promising anticancer potential. Halodule uninervis, a seagrass, contains a variety of bioactive compounds that provide various pharmacological properties. However, its potential anticancer effects against breast cancer remain largely unexplored.</p><p><strong>Methods: </strong>HRLC-MS analysis was conducted to identify the phytochemicals in the ethanolic extract of H. uninervis leaves. Several publicly available databases, including SEA, STP, MALACARDS, DISGENET, and OMIM, were used to identify target genes. Protein-protein interaction (PPI) networks, gene ontology, and pathway analysis were carried out through the STRING and DAVID databases. Molecular docking was performed by Autodock Vina, while molecular dynamics (MD) simulations and MMPBSA analyses were conducted using GROMACS, demonstrating the stability of the complexes up to 200 ns.</p><p><strong>Results: </strong>The top five therapeutically active phytochemicals were Quercetin, Arborinine, Methyl 3,4,5- trimethoxycinnamate, Citreorosein, and Scopolin. The five hub genes, AKT1, EGFR, TNF, ESR1, and GAPDH, were found by network analyses. Molecular docking and MD simulation demonstrate that Quercetin and Citreorosein are the best phytochemicals exhibiting the highest affinities to breast cancer targets AKT1, EGFR, and ESR1.</p><p><strong>Discussion: </strong>For the first time, this in-silico study investigates the potential of citreorosein and quercetin, two phytochemicals predominantly found in H. uninervis leaves, to inhibit the activity of AKT1, EGFR, and ESR1. However, as these results are based on predictive computational analyses, further experimental validation is necessary to confirm their precise mechanisms of action.</p><p><strong>Conclusion: </strong>Phytochemicals, namely Quercetin and Citreorosein, may have an impact on the progression of breast cancer by binding to the key targets AKT1, ESR1, and EGFR.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Health Potential of Myricetin: Bio-accessibility, Safety Considerations, and Therapeutic Mechanisms.","authors":"Rashmi Pathak, Phool Chandra, Neetu Sachan","doi":"10.2174/0113816128369420250707163438","DOIUrl":"https://doi.org/10.2174/0113816128369420250707163438","url":null,"abstract":"<p><p>Myricetin, a naturally occurring flavanol, has gained significant attention due to its diverse pharmacological properties, including antioxidant, anti-inflammatory, anticancer, antidiabetic, and neuroprotective effects. Found abundantly in various plant families, such as Myricaceae, Anacardiaceae, and Polygonaceae, Myricetin exerts its therapeutic effects by modulating key cellular pathways, including Nrf2/HO-1, MAPK, and PI3K/Akt signaling. This review systematically evaluates Myricetin's bioaccessibility, pharmacokinetics, and therapeutic potential, highlighting its role in modulating oxidative stress, inhibiting tumor proliferation, and protecting against neurodegenerative diseases. Despite its promising benefits, Myricetin exhibits limited bioavailability due to poor aqueous solubility and extensive phase II metabolism (glucuronidation and sulfation). Additionally, Myricetin interacts with cytochrome P450 enzymes (CYP3A4, CYP2C9, CYP2D6), potentially altering drug metabolism and increasing the risk of drug interactions. Toxicological studies indicate an LD50 of 800 mg/kg in mice, with potential hepatic and renal toxicity at high doses, mainly due to redox cycling and quinone formation. While Myricetin shows excellent radical-scavenging properties, it may act as a pro-oxidant in the presence of metal ions, leading to oxidative stress and cellular damage. This review underscores the need for advanced formulation strategies to enhance bioavailability and mitigate toxicity risks. Future clinical investigations are essential to establish optimal therapeutic dosages, assess long-term safety, and validate Myricetin's potential as a nutraceutical and therapeutic agent in chronic diseases.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}