Pharmaceuticals最新文献

{"title":"Polyphenolic Composition, Mineral Profile, and Biological Activities in Different Organs of Alpine Woundwort-Insights into Antioxidant and Enzyme Inhibitory Potential.","authors":"Sabina Lachowicz-Wiśniewska, Ireneusz Ochmian, Jan Oszmiański, Rafał Wiśniewski, Małgorzata Bernatek, Paweł Rubiński, Daniela De Vita","doi":"10.3390/ph18050674","DOIUrl":"10.3390/ph18050674","url":null,"abstract":"<p><p><b>Background:</b><i>Stachys alpina</i> is a medicinal plant from the Lamiaceae family whose biological potential remains poorly explored. <b>Methods:</b> The aim of this study was to comprehensively assess the pol-yphenol profile, macro- and microelement composition, and the antioxidant, an-ti-diabetic, and anti-obesity activities of various plant organs (leaves, flowers, stems, and roots). <b>Results:</b> The leaves and flowers exhibited the highest concentration of phenolic compounds, while anthocyanins were detected exclusively in the flowers (215.05 mg/100 g dry matter (dm)) and constituted 3% of the total polyphenols. Verbas-coside and chlorogenic acid were the most abundant polyphenols, reaching 4618.88 and 3277.83 mg/ 100 g dm in the leaves. The highest ABTS and FRAP scavenging activity was observed in leaves (19.30 and 7.62 mmol TE/g dm, respectively). Principal component analysis demonstrated a strong correlation between polyphenol content and antioxidant activity (ABTS-r= 0.87 and FRAP-r = 0.90), which was further confirmed by Pearson's correlation coefficients. The study also highlighted the significant impact of mineral composition on biological activity-calcium and magnesium dominated in stems (10,100 and 3900 mg/kg) and in roots (9200 and 3100 mg/kg), supporting the functioning of an-tioxidant enzymes, while zinc and manganese in leaves (89.43 and 155.33 mg/kg) con-tributed to intense metabolic processes. <b>Conclusions:</b><i>S. aplina</i> could serve as a valuable source of natural antioxidants and enzyme inhibitors associated with glucose and lipid metabolism, suggesting its promising application in the prevention and management of metabolic disorders..</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Protective Effects of Traditional Antidiabetic Medications and Novel Antihyperglycemic Agents in Diabetic Rodent Models.","authors":"Cosmin Gabriel Tartau, Ianis Kevyn Stefan Boboc, Liliana Mititelu-Tartau, Maria Bogdan, Beatrice Rozalina Buca, Liliana Lacramioara Pavel, Cornelia Amalinei","doi":"10.3390/ph18050670","DOIUrl":"10.3390/ph18050670","url":null,"abstract":"<p><p>Type 2 Diabetes (T2D) is a complex metabolic disorder that affects multiple organs, leading to severe complications in the pancreas, kidneys, liver, and heart. Prolonged hyperglycemia, along with oxidative stress and chronic inflammation, plays a crucial role in accelerating tissue damage, significantly increasing the risk of diabetic complications such as nephropathy, hepatopathy, and cardiovascular disease. This review evaluates the protective effects of various antidiabetic treatments on organ tissues affected by T2D, based on findings from experimental animal models. Metformin, a first-line antidiabetic agent, has been widely recognized for its ability to reduce inflammation and oxidative stress, thereby mitigating diabetes-induced organ damage. Its protective role extends beyond glucose regulation, offering benefits such as improved mitochondrial function and reduced fibrosis in affected tissues. In addition to traditional therapies, new classes of antidiabetic drugs, including sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists not only improve glycemic control but also exhibit nephroprotective and cardioprotective properties by reducing glomerular hyperfiltration, oxidative stress, and inflammation. Similarly, GLP-1 receptor agonists have been associated with reduced hepatic steatosis and enhanced cardiovascular function. Preclinical studies suggest that tirzepatide, a dual GLP-1/gastric inhibitory polypeptide receptor agonist may offer superior metabolic benefits compared to conventional GLP-1 agonists by improving β-cell function, enhancing insulin sensitivity, and reducing fatty liver progression. Despite promising preclinical results, differences between animal models and human physiology pose a challenge. Further clinical research is needed to confirm these effects and refine treatment strategies. Future T2D management aims to go beyond glycemic control, emphasizing organ protection and long-term disease prevention.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT.","authors":"Batoul Dhaini, Joël Daouk, Hervé Schohn, Philippe Arnoux, Valérie Jouan-Hureaux, Albert Moussaron, Agnès Hagege, Mathilde Achard, Samir Acherar, Tayssir Hamieh, Céline Frochot","doi":"10.3390/ph18050672","DOIUrl":"10.3390/ph18050672","url":null,"abstract":"<p><p>In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV-visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repositioning FDA-Approved Sulfonamide-Based Drugs as Potential Carbonic Anhydrase Inhibitors in <i>Trypanosoma cruzi</i>: Virtual Screening and In Vitro Studies.","authors":"Eyra Ortiz-Pérez, Adriana Moreno-Rodríguez, Timoteo Delgado-Maldonado, Jessica L Ortega-Balleza, Alonzo González-González, Alma D Paz-González, Karina Vázquez, Guadalupe Avalos-Navarro, Simone Giovannuzzi, Claudiu T Supuran, Gildardo Rivera","doi":"10.3390/ph18050669","DOIUrl":"10.3390/ph18050669","url":null,"abstract":"<p><p><b>Background/Objectives:</b> α-carbonic anhydrase (α-TcCA) has emerged as a promising drug target in <i>T. cruzi</i>, the causative agent of Chagas disease in the Americas. Sulfonamides, known inhibitors of CAs, bind to the zinc ion on the enzyme's active site. This study proposes the repositioning of sulfonamide-based drugs to identify new trypanocidal agents. <b>Method:</b> Ligand-based virtual screening and molecular docking analysis were performed on FDA-approved drugs targeting α-TcCA. These compounds were evaluated in vitro and ex vivo against the A1 and NINOA strains, followed by enzymatic assays. <b>Results:</b> Four sulfonylureas were selected: glimepiride (Glim), acetohexamide (Ace), gliclazide (Glic), and tolbutamide (Tol). Ace and Tol had half-maximal inhibitory concentration (IC₅₀) values similar or better than reference drugs against the NINOA strain in the epimastigote and trypomastigote stages, while Glic and Glim had the highest activity against the A1 strain (epimastigotes and amastigotes). Notably, Ace had the highest trypanocidal activity against all stages in NINOA, with IC₅₀ values of 6.5, 46.5, and 46 μM for epimastigotes, trypomastigotes, and amastigotes, respectively. Additionally, Ace inhibited α-TcCA with K_I = 5.6 μM, suggesting that its trypanocidal effect is associated to the enzyme inhibition. <b>Conclusions:</b> This study supports the repositioning of FDA-approved sulfonamide-based hypoglycaemic agents as trypanocidal compounds. Future studies should focus on structural modifications to improve selectivity. Integrating docking, parasitological, and enzymatic data is crucial for optimizing drug candidates for Chagas disease.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity.","authors":"Lauren A Ling, Asma Boukhalfa, Andrew H Kung, Vicky K Yang, Howard H Chen","doi":"10.3390/ph18050671","DOIUrl":"10.3390/ph18050671","url":null,"abstract":"<p><p>Autophagy, an evolutionarily conserved process, plays an important role in cellular homeostasis and human diseases. Cardiovascular dysfunction, which presents during cancer treatment or in cancer-free individuals years after treatment, is a growing clinical challenge. Millions of cancer survivors and patients face an unpredictable risk of developing cardiotoxicity. Cardiotoxicity due to cancer treatment, as well as cancer progression, has been linked to autophagy dysregulation. Modulating autophagy has been further proposed as a therapeutic treatment for both cancer and cardiovascular disorders. The safe and effective use of autophagy modulation as a cardioprotective strategy during cancer treatment especially requires careful consideration and experimentation to minimize the impact on cancer treatment. We focus here on recent advances in targeted autophagy modulation strategies that utilize interdisciplinary approaches in biomedical sciences and are potentially translatable to treat cardiotoxicity and improve cancer treatment outcomes. This review highlights non-small molecule autophagy modulators to enhance targeted therapy, nanomedicine for autophagy modulation and monitoring, and in vitro models and future experiments needed to bring novel autophagy discoveries from basic research to clinical translation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticonvulsant Profiles of Three Hemorphin-4 Analogs with Rhodamine B in Mice.","authors":"Jana Tchekalarova, Miroslav Rangelov, Ivan Iliev, Nadezhda Todorova, Tsveta Stoyanova, Lian Nedelchev, Petar Todorov","doi":"10.3390/ph18050673","DOIUrl":"10.3390/ph18050673","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hemorphins, considered to be bioactive atypical oligopeptides, are products of hemoglobin metabolism. Recently, our team reported the synthesis and characterization of three N-modified analogs of hemorphin-4 (H4) with rhodamine B (Rh). In the present study, the Rh-1, Rh-2, and Rh-3 compounds were intracerebroventricularly infused at doses of 1, 2.5, 5, and 10 µg/5 µL, respectively, and evaluated for their antiseizure activity in 6-Hz and maximal electroshock (MES) tests and in a pentylenetetrazol (PTZ)-induced kindling model in mice. Phenytoin and diazepam were used as the reference drugs. The role of opioid receptors (ORs) underlying their mechanism of action was also evaluated in silico and pharmacologically. <b>Results</b>: The three Rh-H4 compounds showed a good safety profile at a concentration of 100 µg/mL in the mouse embryonic fibroblasts. They suppressed psychomotor seizures and seizure spreading as follows: Rh-1 at doses of 5 and 10 µg/5 µL, Rh-2 at the highest dose, and Rh-3 at doses of 1-10 µg/5 µL, respectively. Administered at doses of 5 µg/5 µL (Rh-1 and Rh-3) and 10 µg/5 µL (Rh-2), the compounds suppressed clonic seizures in the kindled mice comparable to the reference drug diazepam. A combination of selective delta (DOR), kappa (KOR), and mu (MOR) OR antagonists with the highest doses of the Rh-1, Rh-2, and Rh-3 compounds was used to elucidate the possible role of ORs in the underlying mechanism related to their protective activity against seizure spread. Only the selective DOR antagonist, natrindole, suppressed the effect of the Rh-1 peptide analog on seizures. The OR antagonist naloxone prevented the antiseizure activity of Rh-1 in the kindled mice. The results of docking analysis also showed the model-specific interaction of the three Rh-H4 compounds with the OR. <b>Conclusions</b>: Our results suggest that the antiseizure activity of Rh-1 is mediated by the OR, and in particular by the DOR, while the mechanism underlying the antiseizure effect of Rh-3 is more complex and may involve other receptors.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota-Targeted Intervention of Hyperlipidemia Using <i>Monascus</i>-Fermented Ginseng.","authors":"Qing Zhou, Cuiting Yang, Mingyue Jia, Qingsong Qu, Xinhui Peng, Weishuo Ren, Guoqing Li, Yueyang Xie, Bingxuan Li, Xinyuan Shi","doi":"10.3390/ph18050661","DOIUrl":"10.3390/ph18050661","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of <i>Monascus</i>-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). <b>Methods:</b> The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. <b>Results:</b> FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. <b>Conclusions:</b> These findings demonstrate FMT's therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy and Safety of Tirzepatide in Patients with Diabetes and/or Obesity: Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Ligang Liu, Hekai Shi, Merilyn Xie, Yuxiao Sun, Milap C Nahata","doi":"10.3390/ph18050668","DOIUrl":"10.3390/ph18050668","url":null,"abstract":"<p><p><b>Background:</b> Obesity and type 2 diabetes (T2D) are major public health concerns. Tirzepatide has shown promise in recent clinical trials. This systematic review and meta-analysis aim to evaluate the efficacy and safety of tirzepatide in adults with obesity or type 2 diabetes, compared to placebo, GLP-1 receptor agonists (GLP-1 RAs), and insulin. <b>Method</b>: PubMed, Embase, and the Cochrane Library were searched on 17 January 2024, focusing on phase II and III randomized controlled trials (RCTs). We included studies involving adults with T2D or obesity, comparing tirzepatide to placebo, GLP-1 RAs, or insulin. The primary outcomes were the proportion of participants achieving ≥5%, ≥10%, and ≥15% weight loss targets. Secondary outcomes included changes in body weight, waist circumference, HbA1c levels, and blood pressure. Safety outcomes focused on adverse event rates. Meta-analyses were performed, and risk of bias was assessed using the Cochrane Risk-of-Bias tool version 2. <b>Results</b>: Fourteen RCTs involving 14,713 patients were included. Tirzepatide significantly increased the proportion of participants achieving weight loss targets, and reduced body weight, waist circumference, HbA1c, and blood pressure versus placebo and insulin. Compared with GLP-1 RAs, tirzepatide provided comparable or better outcomes in weight loss, waist circumference, and glycemic control. The incidence of gastrointestinal adverse events was significantly higher at all doses of tirzepatide compared to placebo and insulin. When compared with GLP-1 RAs, higher doses of tirzepatide were associated with increased risk of nausea, diarrhea, and decreased appetite, but not vomiting. <b>Conclusions:</b> Tirzepatide is an effective option for managing weight and improving metabolic outcomes in patients with T2D or obesity. However, it is associated with an increased risk of gastrointestinal adverse events, especially at higher doses. Therefore, close monitoring should be considered in clinical practice. <b>Registration</b>: PROSPERO CRD42021283449.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructose-1,6-Bisphosphate Reduces Chronic Constriction Injury Neuropathic Pain in Mice by Targeting Dorsal Root Ganglia Nociceptive Neuron Activation.","authors":"Amanda Martins Dionisio, Paula de Azevedo Oliveira Milanez, Ana Carla Zarpelon-Schutz, Sandra Satie Mizokami, Mariana Marques Bertozzi, Kelly Megumi Yaekashi, Doumit Camilios-Neto, Sergio Marques Borghi, Rubia Casagrande, Waldiceu A Verri","doi":"10.3390/ph18050660","DOIUrl":"10.3390/ph18050660","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Fructose-1,6-bisphosphate (FBP) is an intermediate product of the glycolytic pathway with analgesic effect in acute inflammatory pain model via the production of adenosine. However, whether FBP is active in neuropathic pain is unknown. Therefore, we reason that it would be suitable to investigate the analgesic effect and mechanism of action of FBP in a model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain in mice. <b>Methods:</b> After CCI induction, mice received FBP, adenosine, A1 and/or A2A receptor antagonists, and/or inhibitors of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/ATP sensitive K channels (KATP) signaling pathway. <b>Results:</b> FBP (up to 85%) and adenosine (up to 84%) inhibited the mechanical hyperalgesia (electronic aesthesiometer) induced by CCI with similar profiles. FBP analgesia was dependent on adenosine because adenosine A1 and A2A receptors antagonists diminished FPB activity (100% and 79%, respectively). FBP analgesia was also dependent on activating the NO/cGMP/PKG/KATP signaling pathway. Furthermore, FBP treatment increased the production of NO in cultured dorsal root ganglia (DRG) neurons (100% increase), whereas neuronal nitric oxide synthase (nNOS) inhibition decreased (up to 70%) the analgesic effect of FBP. We also observed that FBP reduced the calcium levels of transient receptor potential ankyrin 1 (TRPA1)⁺ DRG neurons (85%) and paw-flinching triggered by TRPA1 activation (38%). <b>Conclusions</b>: FBP reduced neuropathic pain by reducing DRG neuron activation. The mechanisms involved the activation of adenosine A1 and A2A receptors to trigger the analgesic NO/cGMP/PKG/KATP signaling pathway and reducing TRPA1⁺ DRG neuron activity.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Anti-Lung Cancer Mechanisms of <i>Taraxacum officinale</i> Based on Network Pharmacology and Multidimensional Experimental Validation.","authors":"Jianing Liu, Hailing Yang, Ran Liu, Dongjin Sun, Yongbao Liu, Jing Lu, Jinbiao Liu, Junrui Lu","doi":"10.3390/ph18050663","DOIUrl":"10.3390/ph18050663","url":null,"abstract":"<p><p><b>Background:</b><i>Taraxacum officinale</i>(commonly known as dandelion) is a medicinal and edible plant, with the entire plant being used for therapeutic purposes. Studies have demonstrated that dandelion exhibits inhibitory effects against various types of cancer. However, research on its potential for lung cancer (LC) treatment is limited, and the specific compounds responsible for its anticancer effects, as well as the underlying mechanisms, remain unclear. <b>Methods</b>: This study aimed to elucidate the underlying pharmacological mechanisms by which dandelion exerts therapeutic effects against LC. Initially, active compounds of dandelion and their corresponding targets were retrieved from public databases. Subsequently, network pharmacology approaches were applied to identify LC-associated disease targets. By integrating drug-specific targets and disease-related targets, a comprehensive dandelion-lung cancer interaction network was established. Protein-protein interaction (PPI) analyses and functional enrichment studies were further performed to uncover potential molecular mechanisms. Additionally, molecular docking and molecular dynamics (MD) simulations were conducted to evaluate binding interactions between critical active constituents and core targets. To experimentally validate these findings, in vitro cellular assays combined with scanning electron microscopy (SEM) were employed to investigate the anticancer effects of taraxasterol, a key bioactive sterol compound isolated from dandelion, on LC cells. <b>Results</b>: Our analyses identified 58 active compounds in dandelion linked to 614 potential targets, of which 228 targets were associated with LC. The PPI network highlighted 16 core targets, notably TP53, CASP3 and EGFR. Functional enrichment analysis suggested that dandelion might exert its anticancer effects by modulating the tumor microenvironment through the regulation of these critical targets. Molecular docking results demonstrated stable binding interactions between major active compounds and the identified core targets. Furthermore, the anticancer activity of taraxasterol was experimentally validated through in vitro assays and SEM-based morphological assessments, confirming its inhibitory effects on A549 lung cancer cells. <b>Conclusions</b>: Collectively, our findings reveal a multi-targeted therapeutic mechanism of dandelion against LC and support its potential development as a novel natural candidate for lung cancer treatment.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12114748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}