Pharmaceuticals最新文献

{"title":"Behavioral and Biochemical Insights into the Therapeutic Potential of Mitocurcumin in a Zebrafish-Pentylenetetrazole (PTZ) Epilepsy Model.","authors":"Alin Dumitru Ciubotaru, Carmen-Ecaterina Leferman, Bogdan-Emilian Ignat, Anton Knieling, Irina Mihaela Esanu, Delia Lidia Salaru, Liliana Georgeta Foia, Bogdan Minea, Luminita Diana Hritcu, Cristina Daniela Dimitriu, Laura Stoica, Ioan-Adrian Ciureanu, Alin Stelian Ciobica, Andrei Neamtu, Bogdan Alexandru Stoica, Cristina Mihaela Ghiciuc","doi":"10.3390/ph18030382","DOIUrl":"10.3390/ph18030382","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Epilepsy is a complex neurological disorder with a strong link to oxidative stress, which contributes to seizure susceptibility and neuronal damage. This study aims to investigate the effects of curcumin (Cur), sodium valproate (VPA), and mitocurcumin (MitoCur), a mitochondria-targeted curcumin, on behavioral and oxidative stress parameters in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures. <b>Methods:</b> Adult zebrafish were exposed to two concentrations (0.25 and 0.5 µM for Cur and MitoCur; 0.25 and 0.5 mM for VPA). Behavioral assessments, including locomotion, spatial exploration, and directional movement, were conducted using EthoVision XT tracking software. Oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant status (TAS), were analyzed in brain homogenates. <b>Results:</b> Behavioral analyses indicated dose-dependent effects, with higher doses generally reducing activity. MitoCur at 0.25 µM enhanced antioxidant defenses and reduced oxidative damage, while higher doses exhibited a pro-oxidant shift. VPA at 0.25 mM improved TAS without significantly altering MDA levels. <b>Conclusions:</b> These findings emphasize the importance of dose optimization in antioxidant-based epilepsy treatments and highlight the potential of MitoCur as a targeted therapeutic option.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721110","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 Impact of Montelukast Duration on the Risk of Neuropsychiatric Disorders in Children with Asthma: A Population-Based Cohort Study.","authors":"Wei-Te Lei, Chien-Yu Lin, Szu-Hung Chu, Li-Ching Fang, Yu-Hsuan Kao, Po-Li Tsai, Yu-Wen Lin, Fung-Chang Sung, Shu-I Wu","doi":"10.3390/ph18030379","DOIUrl":"10.3390/ph18030379","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Asthma is one of the most common chronic diseases in children, and montelukast is widely prescribed to manage symptoms. However, concerns have emerged regarding its potential association with neuropsychiatric disorders. This study aims to investigate the impact of montelukast duration on neuropsychiatric risks in children with asthma. <b>Methods:</b> A cohort study was conducted using Taiwan's National Health Insurance Research Database (NHIRD), including children diagnosed with asthma between 2004 and 2007. A total of 14,606 children in the montelukast cohort and 8432 in the non-montelukast cohort were analyzed, with propensity score matching applied to reduce confounding bias. Neuropsychiatric outcomes, including Tics/Tourette's syndrome, were evaluated using Cox proportional hazard models. <b>Results:</b> Overall, montelukast use did not increase the risk of neuropsychiatric disorders. However, among children aged 6-15 years, prolonged use beyond 63 days was associated with a significantly elevated risk of Tics/Tourette's syndrome, with a 2.6-fold increase observed in girls and a 1.8-fold increase in boys. Conversely, shorter montelukast use in children aged 0-6 years was linked to a lower risk of neuropsychiatric disorders. <b>Conclusions:</b> Although montelukast generally does not elevate neuropsychiatric risks, extended use in older children may increase the likelihood of developing Tics/Tourette's syndrome. These findings highlight the importance of cautious prescribing in pediatric asthma management. Further research is necessary to validate these associations and inform clinical decision making.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721189","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":"BuZhong YiQi Formula Alleviates Diabetes-Caused Hyposalivation by Activating Salivary Secretion Pathway in the Parotid and Submandibular Glands of Rats.","authors":"Ming-Yu Wang, Zhen-Ran Hu, Liang Wang, Xin-Xin Zeng, Xiang-Ke Li, Guo-Jun Fei, Jing-Li Zhang, Jing-Ru Chen, Ze-Min Yang","doi":"10.3390/ph18030377","DOIUrl":"10.3390/ph18030377","url":null,"abstract":"<p><p><b>Background/Objectives</b>: BuZhong Yiqi Formula (BZYQF) has significant ameliorative effects on type 2 diabetes mellitus (T2DM). However, its efficacy in alleviating the hyposalivation caused by T2DM needs to be confirmed, and its mechanism is unclear. <b>Methods</b>: Network pharmacology and molecular docking were combined to analyze the molecular mechanism by which BZYQF alleviates T2DM-caused hyposalivation. A T2DM rat model was induced to evaluate the efficacy of BZYQF. The total saliva before and after acid stimulation was collected to determine the salivary flow rate and salivary alpha-amylase (sAA) activity. The parotid (PG) and submandibular glands (SMG) of experimental rats were removed to perform histopathology observation, biochemical indicator determination, and expression detection of signaling molecules in the salivary secretion pathway. <b>Results</b>: The present study screened out 1014 potential targets of BZYQF regarding the treatment of T2DM. These targets were mainly involved in the formation of the receptor complex, exercising the neurotransmitter receptor activity and regulating secretion. They were significantly enriched in the salivary secretion pathway of β1-AR/PKA/AMY1 and CHRM3/IP3R/AQP5. Furthermore, in BZYQF, nine validated compounds were able to dock into the active site of β1-AR, and three validated compounds were able to dock into the active site of CHRM3. Animal experiments confirmed that BZYQF significantly reduces fasting blood glucose, total cholesterol and triglyceride levels; enhances insulin level and HOMA-IS (<i>p</i> < 0.05); and increases salivary flow rate (Basal: increase from 21.04 ± 14.31 to 42.65 ± 8.84 μL/min, effect size of Cohen's d = 6.80, <i>p</i> = 0.0078; Stimulated: increase from 36.88 ± 17.48 to 72.63 ± 17.67 μL/min, effect size of Cohen's d = 7.61, <i>p</i> = 0.0025) and sAA activity (Basal: increase from 0.68 ± 0.32 to 2.17 ± 0.77 U/mL, effect size of Cohen's d = 9.49, <i>p</i> = 0.0027; Stimulated: increase from 1.15 ± 0.77 to 4.80 ± 1.26 U/mL, effect size of Cohen's d = 13.10, <i>p</i> = 0.0001) in basal and stimulated saliva in T2DM rats. Further mechanistic studies revealed that BZYQF reduces glucose and lipid accumulation, enhances acetylcholine content, improves pathological lesions and inflammation, and significantly increases the expression of salivary secretion pathway signaling molecules, including PKA, IP3R, β1-AR, AQP5, CHRM3, and AMY1 in the PG and SMG of T2DM rats (<i>p</i> < 0.05). <b>Conclusions</b>: The present study demonstrated that BZYQF is able to alleviate T2DM-caused hyposalivation by improving glucose metabolism and activating the salivary secretion pathway in the PG and SMG of T2DM rats. This study might provide a novel rationale and treatment strategy for BZYQF in diabetes-induced hyposalivation in a clinical setting.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721058","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":"Synthesis, Structure, and Stability of Copper(II) Complexes Containing Imidazoline-Phthalazine Ligands with Potential Anticancer Activity.","authors":"Łukasz Balewski, Iwona Inkielewicz-Stępniak, Maria Gdaniec, Katarzyna Turecka, Anna Hering, Anna Ordyszewska, Anita Kornicka","doi":"10.3390/ph18030375","DOIUrl":"10.3390/ph18030375","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Recently, there has been great interest in metallopharmaceuticals as potential anticancer agents. In this context, presented studies aim to synthesize and evaluate of two copper(II) complexes derived from phthalazine- and imidazoline-based ligands against on three human cancer cell lines: cervix epithelial cell line (HeLa), breast epithelial-like adenocarcinoma (MCF-7), and triple-negative breast epithelial cancer cell line (MDA-MB-231), as well as non-tumorigenic cell line (HDFa). Moreover their antimicrobial, and antioxidant properties were assessed. &lt;b&gt;Methods&lt;/b&gt;: The synthetized compounds-both free ligands &lt;b&gt;L1&lt;/b&gt;, &lt;b&gt;L2&lt;/b&gt;, &lt;b&gt;L3&lt;/b&gt; and copper(II) complexes &lt;b&gt;C1&lt;/b&gt; and &lt;b&gt;C2&lt;/b&gt;-were characterized by elemental analysis, infrared spectroscopy. Additionally, a single-crystal X-ray diffraction studies we performed for free ligand &lt;b&gt;L3&lt;/b&gt; and its copper(II) complex &lt;b&gt;C2&lt;/b&gt;. The stability of Cu(II)-complexes &lt;b&gt;C1&lt;/b&gt; and &lt;b&gt;C2&lt;/b&gt; was evaluated by UV-Vis spectroscopy. The cytotoxic potency of free ligands and their copper(II) complexes was estimated on HeLa, MCF-7, MDA-MB-231, as well as non-cancerous HDFa by use of an MTT assay after 48 h of incubation. Moreover, the antimicrobial activity of ligands &lt;b&gt;L1&lt;/b&gt; and &lt;b&gt;L3&lt;/b&gt; and their copper(II) complexes &lt;b&gt;C1&lt;/b&gt; and &lt;b&gt;C2&lt;/b&gt; was evaluated using reference strains of the following bacteria and yeasts: &lt;i&gt;Staphylococcus aureus&lt;/i&gt;, &lt;i&gt;Escherichia coli&lt;/i&gt;, and &lt;i&gt;Candida albicans&lt;/i&gt;. The free radical scavenging properties of free ligands &lt;b&gt;L1&lt;/b&gt;, &lt;b&gt;L3&lt;/b&gt; and the corresponding copper(II) complexes &lt;b&gt;C1&lt;/b&gt;, &lt;b&gt;C2&lt;/b&gt; was tested with two colorimetric methods-ABTS, DPPH, and reduction ability assay (FRAP). Additionally, the ADME webtool was used to assess the drug-likeness of the synthesized compounds, as well as their physicochemical and pharmacokinetic properties. &lt;b&gt;Results&lt;/b&gt;: Copper(II) complex &lt;b&gt;C2&lt;/b&gt; exhibited antitumor properties towards MDA-MB-231 compared with Cisplatin (cancer cell viability rate of 23.6% vs. 22.5%). At a concentration of 200 μg/mL, complexes &lt;b&gt;C1&lt;/b&gt; and &lt;b&gt;C2&lt;/b&gt; were less cytotoxic than the reference Cisplatin against a normal, non-cancerous skin fibroblast cell line (HDFa). According to in vitro tests, &lt;b&gt;C2&lt;/b&gt; reduced the viability of HeLa, MCF-7, and MDA-MB-231 cells by about 57.5-81.2%. It was evident that all compounds were devoid of antibacterial or antifungal activity. In vitro assays revealed that a moderate antiradical effect was observed for free ligand &lt;b&gt;L1&lt;/b&gt; containing phthalazin-1(2&lt;i&gt;H&lt;/i&gt;)-imine in the ABTS radical scavenging assay (IC&lt;sub&gt;50&lt;/sub&gt; = 23.63 µg/mL). &lt;b&gt;Conclusions&lt;/b&gt;: The anticancer studies revealed that the most potent compound was copper(II) complex &lt;b&gt;C2&lt;/b&gt; bearing a phthalazin-1(2&lt;i&gt;H&lt;/i&gt;)-one scaffold. None of the tested compounds showed antimicrobial or antifungal activity. This feature seems to be beneficial in terms of their potential uses as anticancer agents in the ","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721247","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":"Bioactive Substances and Skin Health: An Integrative Review from a Pharmacy and Nutrition Perspective.","authors":"Rafael Jesús Giménez Martínez, Francisco Rivas García, Joan Carles March Cerdá, Ángela Hernández-Ruíz, Martha Irene González Castro, María-Isabel Valverde-Merino, Felipe José Huertas Camarasa, Fuensanta Lloris Meseguer, Margarita López-Viota Gallardo","doi":"10.3390/ph18030373","DOIUrl":"10.3390/ph18030373","url":null,"abstract":"<p><p>The skin is one of the largest and most important organs of our body. There are numerous factors that are related to skin health, including lifestyle factors, nutrition, or skin care. Bioactive substances from plant and marine extracts play a key role in skin health. The aim of this research was to compile the main evidence on skin and bioactive substances. An integrative review was performed, reporting the main findings according to PRISMA (2020). Thirteen search equations were developed. After the applications of the equations and the process of screening and selection of articles, 95 references were compiled. The main results related to bioactive compounds were classified into food-derived components, nutraceuticals, symbiotics, active substances of marine origin, and substances from plant extracts). There are several factors that indicate that the use of bioactive compounds are interesting for skin health, highlighting some dietary nutrients, substances obtained from plant extracts and metabolites of marine origin that, showing anti-inflammatory and antimicrobial effects, are related to the improvement of some skin conditions or are active principles for cosmetics.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721118","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":"Gambogenic Acid Suppresses Malignant Progression of Non-Small Cell Lung Cancer via GCH1-Mediated Ferroptosis.","authors":"Menghan Wang, Jiao Liu, Wenxi Yu, Jiancang Shao, Yang Bao, Mingming Jin, Qingqing Huang, Gang Huang","doi":"10.3390/ph18030374","DOIUrl":"10.3390/ph18030374","url":null,"abstract":"<p><p><b>Introduction:</b> Non-small cell lung cancer (NSCLC) is a lethal type of lung cancer (LC) with a 5-year survival rate of 19%. Because drug resistance typically develops following chemotherapy, radiotherapy, and immunotherapy, a novel NSCLC therapeutic strategy is urgently demanded. Gambogenic acid (GNA), a major bioactive ingredient isolated from gamboge, has multipotent antitumor effects, although activity against NSCLC is unknown. <b>Methods:</b> CCK8, ethynyl deoxyuridine (EdU), the plate colony formation assay, and the transwell and wound healing (WH) assay were used to study the effect of GNA on the proliferation and migration ability of NSCLC. Flow cytometry was used to detect apoptosis and the cell cycle. Proteomic analysis and LiP-SMap were used to detect the downstream target of GNA. Ferroptosis inhibitor ferrostatin-1 was used to detect the effect of GNA on NSCLC ferroptosis. Overexpressing GCH1 was used for a rescue experiment. Subcutaneous tumor and pulmonary metastasis in a mouse model were used to study the effect of GNA on NSCLC growth and metastasis. <b>Results:</b> The results of the present study showed that GNA inhibited the proliferation and migration of NSCLC cells in a dose- and time-dependent manner, which arrested the cell cycle in the G0/G1 phase. In vivo data revealed that GNA inhibited tumor growth and lung metastasis. Proteomic analysis found that GNA significantly inhibited the expression of GTP cyclohydrolase 1 (GCH1). LiP-SMap analysis showed that GNA interacted with ILE248 and ARG249 of GCH1. GCH1 overexpression had a similar role to the ferroptosis inhibitor ferrostatin-1 and restored cell proliferation and migration after GNA treatment. Also, GNA promoted reactive oxygen species (ROS) accumulation, which reduced mitochondrial membrane potential. GCH1 overexpression or ferrostatin-1 treatment reversed GNA regulation of ROS accumulation and mitochondrial membrane potential inhibition. <b>Conclusions:</b> Taken together, these findings confirmed that GNA suppressed the malignant progression of NSCLC by inducing GCH1-mediated ferroptosis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721111","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":"A Preliminary Report on the Effects of Daridorexant in Patients with Comorbid Insomnia and Substance Use Disorders.","authors":"Marco Di Nicola, Maria Pepe, Lorenzo Bonomo, Miriam Milintenda, Isabella Panaccione, Roberto Brugnoli, Gabriele Sani","doi":"10.3390/ph18030378","DOIUrl":"10.3390/ph18030378","url":null,"abstract":"<p><p><b>Background</b>. Sleep disturbances are frequent in patients with substance use disorders (SUDs) and are associated with craving and addiction relapses, leading to increased clinical severity and detrimental outcomes. Daridorexant, a selective dual orexin receptor antagonist, has been approved for persistent insomnia disorder (ID), but specific insights on patients with SUDs are lacking. <b>Methods</b>. This observational, retrospective study investigated the effects of a three-month treatment with daridorexant (50 mg/day) in 41 outpatients with comorbid IDs and SUDs. Improvement in subjective sleep measures, assessed with the Insomnia Severity Index (ISI) and subjective total sleep time, was the primary outcome measure. Changes in anxiety and depression symptoms, quality of life, clinical global severity, and craving were also investigated through the following: Hamilton Anxiety and Depression Rating Scale; Five-item World Health Organization Well-Being Index; Clinical Global Impression Severity Scale; Visual Analog Scale for Craving. <b>Results</b>. All sleep outcomes significantly improved throughout treatment, which was generally safe and well tolerated, with mild and transient drowsiness and sluggishness reported in 21.1% of patients. Similar improvements were observed in psychopathology, quality of life, and craving, and positive correlations were found among ISI scores and anxiety/depression symptoms and craving. An abstinence rate (i.e., absence of any substance use, regardless of the amount, throughout treatment) of 65.8% was also detected at the endpoint. <b>Conclusions</b>. These preliminary findings suggest that daridorexant might represent a promising tool for treating insomnia in patients with SUDs. Identifying interventions effectively targeting insomnia with a good safety/tolerability profile in SUDs is crucial to achieve remission and full functional recovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720930","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":"A 5-Year Update on the Clinical Development of Cancer Cell-Based Vaccines for Glioblastoma Multiforme.","authors":"Almohanad A Alkayyal, Ahmad Bakur Mahmoud","doi":"10.3390/ph18030376","DOIUrl":"10.3390/ph18030376","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is considered one of the most aggressive forms of brain cancer with a 15-month median survival, despite advancements in surgery, radiotherapy, and chemotherapy. The immune-suppressed tumor microenvironment and the blood-brain barrier are major contributors to its poor prognosis and treatment resistance. In the last decade, significant progress has been made in developing cell-based vaccines to boost immune responses against GBM. This review provides an extensive update on recent clinical trials involving various cancer cell vaccines, including ICT-107, the α-type-1 DC vaccine, and others. Although these trials have demonstrated potential improvements in progression-free survival (PFS) and overall survival (OS), the diverse and immune-suppressed nature of GBM poses challenges for consistent therapeutic success. We discuss the details of these trials along with the potential mechanism of vaccine efficacy and immune activations. The findings of these trials highlight the significance of a personalized immunotherapy approach and suggest that patient stratification could significantly advance the clinical management of GBM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720635","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":"Anti-Inflammatory Activity of <i>Cannabis sativa</i> L. Extract in 2,4-Dinitrochlorobenzene-Induced Dermatitis in Rats.","authors":"Renata Wolińska, Maria Zalewska, Piotr Poznański, Agata Nawrocka, Agnieszka Kowalczyk, Mariusz Sacharczuk, Magdalena Bujalska-Zadrożny","doi":"10.3390/ph18030370","DOIUrl":"10.3390/ph18030370","url":null,"abstract":"<p><p><b>Background:</b><i>Cannabis sativa</i> L. and its products are becoming popular for the treatment of inflammatory diseases. One of the main phytocannabinoids contained in cannabis is cannabidiol (CBD), which is a component of numerous cosmetic preparations used to treat inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. However, current data regarding the efficacy and safety of CBD for dermatological indications are limited. Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of high-CBD <i>Cannabis sativa</i> L. extract (eCBD) in a model of AD. <b>Methods:</b> Dermatitis was induced by repeated application of 2,4-dinitrochlorobenzene (DNCB) to the skin of the rats' ears. The therapeutic effect of eCBD was evaluated in behavioral, histopathological, and hematological studies following topical application as an ointment containing 2% CBD. <b>Results:</b> Application of the ointment containing eCBD resulted in attenuation of DNCB-induced inflammation. Interestingly, an anti-edematous effect was more pronounced in rats treated with the eCBD than in rats treated with 1% hydrocortisone ointment. However, eCBD did not reduce the frequency of DNCB-induced scratching, while there was a visible antipruritic effect of 1% hydrocortisone application. Histopathological analysis revealed that both eCBD and 1% hydrocortisone ointments significantly decreased mast cell count compared with the Vaseline control group. Furthermore, treatment with an ointment containing eCBD resulted in a decrease in the number of leukocytes in the blood. <b>Conclusions:</b> Topically administered eCBD had a stronger anti-edematous effect than glucocorticosteroid and differently affected hematological parameters. It is suggested that eCBD has therapeutic potential for the treatment of AD.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721071","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":"A New Era of Muscarinic Acetylcholine Receptor Modulators in Neurological Diseases, Cancer and Drug Abuse.","authors":"Helena Tsimpili, Grigoris Zoidis","doi":"10.3390/ph18030369","DOIUrl":"10.3390/ph18030369","url":null,"abstract":"<p><p>The cholinergic pathways in the central nervous system (CNS) play a pivotal role in different cognitive functions of the brain, such as memory and learning. This review takes a dive into the pharmacological side of this important part of CNS function, taking into consideration muscarinic receptors and cholinesterase enzymes. Targeting a specific subtype of five primary muscarinic receptor subtypes (M1-M5) through agonism or antagonism may benefit patients; thus, there is a great pharmaceutical research interest. Inhibition of AChE and BChE, orthosteric or allosteric, or partial agonism of M1 mAChR are correlated with Alzheimer's disease (AD) symptoms improvement. Agonism or antagonism on different muscarinic receptor subunits may lessen schizophrenia symptoms (especially positive allosteric modulation of M4 mAChR). Selective antagonism of M4 mAChR is a promising treatment for Parkinson's disease and dystonia, and the adverse effects are limited compared to inhibition of all five mAChR. Additionally, selective M5 antagonism plays a role in drug independence behavior. M3 mAChR overexpression is associated with malignancies, and M3R antagonists seem to have a therapeutic potential in cancer, while M1R and M2R inhibition leads to reduction of neoangiogenesis. Depending on the type of cancer, agonism of mAChR may promote cancer cell proliferation (as M3R agonism does) or protection against further tumor development (M1R agonism). Thus, there is an intense need to discover new potent compounds with specific action on muscarinic receptor subtypes. Chemical structures, chemical modification of function groups aiming at action enhancement, reduction of adverse effects, and optimization of Drug Metabolism and Pharmacokinetics (DMPK) will be further discussed, as well as protein-ligand docking.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720694","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}