Pharmaceuticals最新文献

{"title":"Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature.","authors":"Sandra Maria Barbalho, Beatriz Leme Boaro, Jéssica da Silva Camarinha Oliveira, Jiří Patočka, Caroline Barbalho Lamas, Masaru Tanaka, Lucas Fornari Laurindo","doi":"10.3390/ph18010133","DOIUrl":"10.3390/ph18010133","url":null,"abstract":"<p><p>Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like <i>Cleistocalyx nervosum</i> var. paniala, <i>Curcuma longa</i>, <i>Cannabis sativa</i>, and <i>Dioscorea nipponica</i> reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041276","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":"Critical Appraisal of Pharmaceutical Therapy in Diabetic Cardiomyopathy-Challenges and Prospectives.","authors":"Elina Khattab, Michaelia Kyriakou, Elena Leonidou, Stefanos Sokratous, Angeliki Mouzarou, Michael M Myrianthefs, Nikolaos P E Kadoglou","doi":"10.3390/ph18010134","DOIUrl":"10.3390/ph18010134","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a multifaceted disorder with a pandemic spread and a remarkable burden of cardiovascular mortality and morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction, which is accompanied by heart failure (HF) symptoms in the absence of obvious reasons like ischemic heart disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have been proposed, including metabolic disorders (e.g., glycation products), oxidative stress, low-grade inflammation, mitochondrial dysfunction, etc., which should guide the development of new therapeutic strategies. Up to now, HF treatment has not differed between patients with and without diabetes, which limits the expected benefits despite the high cardiovascular risk in the former group. However, DBCM patients may require different management, which prioritize anti-diabetic medications or testing other novel therapies. This review aims to appraise the challenges and prospectives of the individualized pharmaceutical therapy for DBCM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041166","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":"Copper Imparts a New Therapeutic Property to Resveratrol by Generating ROS to Deactivate Cell-Free Chromatin.","authors":"Salooni Khanvilkar, Indraneel Mittra","doi":"10.3390/ph18010132","DOIUrl":"10.3390/ph18010132","url":null,"abstract":"<p><p>Resveratrol, a bioactive phytoalexin, has been extensively studied as a pharmaceutical and nutraceutical candidate for the treatment of various diseases. Although its therapeutic effects have been largely attributed to its anti-oxidant properties, its underlying mechanisms and dose dependency are not well understood. Recent studies have shown that cell-free chromatin particles (cfChPs), which are released daily from billions of dying cells, can enter circulation and be internalized by healthy cells, wherein they trigger various damaging effects, including double-strand DNA breaks. Notably, deactivating cfChPs using a mixture of resveratrol and copper can neutralize their harmful effects. The addition of copper imparts a novel therapeutic property to resveratrol viz. the generation of reactive oxygen species (ROS), which are capable of deactivating cfChPs without damaging the genomic DNA. This perspective article discusses how the deactivation of cfChPs via the ROS generated by combining resveratrol with copper can have multiple therapeutic effects. Exploiting the damaging effects of ROS to deactivate cfChPs and ameliorate disease conditions may be a viable therapeutic approach.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041025","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":"Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications.","authors":"Alice Melani, Marco Bonaso, Letizia Biso, Benedetta Zucchini, Ciro Conversano, Marco Scarselli","doi":"10.3390/ph18010130","DOIUrl":"10.3390/ph18010130","url":null,"abstract":"<p><p>Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to their profound effects on consciousness, emotional processing, mood, and neural plasticity. This review explores the mechanisms underlying psychedelics' effects, focusing on their ability to modulate brain connectivity and neural circuit activity, including the default mode network (DMN), cortico-striatal thalamo-cortical (CSTC) loops, and the relaxed beliefs under psychedelics (REBUS) model. Advanced neuroimaging techniques reveal psychedelics' capacity to enhance functional connectivity between sensory cerebral areas while reducing the connections between associative brain areas, decreasing the rigidity and rendering the brain more plastic and susceptible to external changings, offering insights into their therapeutic outcome. The most relevant clinical trials of 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and lysergic acid diethylamide (LSD) demonstrate significant efficacy in treating treatment-resistant psychiatric conditions such as post-traumatic stress disorder (PTSD), depression, and anxiety, with favorable safety profiles. Despite these advancements, critical gaps remain in linking psychedelics' molecular actions to their clinical efficacy. This review highlights the need for further research to integrate mechanistic insights and optimize psychedelics as tools for both therapy and understanding human cognition.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041108","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":"p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.","authors":"Rui Ding, Tiffany C Edwards, Prithwish Goswami, Daniel J Wilson, Christine D Dreis, Yihong Ye, Robert J Geraghty, Liqiang Chen","doi":"10.3390/ph18010131","DOIUrl":"10.3390/ph18010131","url":null,"abstract":"<p><p><b>Background:</b> p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents. <b>Methods:</b> We designed and synthesized novel p97 inhibitors based on the rearrangement of the central fused ring of our previously reported p97 inhibitors. These compounds were tested for inhibition of p97, cytotoxicity, and antiviral activity against SARS-CoV-2. Molecular docking was also performed on selected inhibitors to shed light on their binding modes. <b>Results:</b> Among these new p97 inhibitors, two compounds possess enhanced anti-p97 activity over their parent compounds. More significantly, these two inhibitors exhibit strong antiviral activity against SARS-CoV-2 at doses with no significant cytotoxicity. Molecular docking reveals no major change of the binding mode relative to that of their parent compounds, further supporting our design strategy. <b>Conclusions:</b> These compounds are structurally novel p97 inhibitors that display low toxicity and possess promising antiviral activity against SARS-CoV-2 and potentially other viruses. Further structural exploration is therefore justified and improved analogs will serve as useful tools for studying p97 as a promising host antiviral target.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040862","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 Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study.","authors":"Hiroya Kitsunai, Yuka Shinozaki, Sho Furusawa, Naoyuki Kitao, Miki Ito, Hiroyoshi Kurihara, Chiho Oba-Yamamoto, Jun Takeuchi, Akinobu Nakamura, Yumi Takiyama, Hiroshi Nomoto","doi":"10.3390/ph18010129","DOIUrl":"10.3390/ph18010129","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated.</p><p><strong>Methods: </strong>A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired <i>t</i>-test or the Wilcoxon signed-rank test.</p><p><strong>Results: </strong>Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, <i>p</i> < 0.001) and FIB-4 index (from 1.04 to 0.96, <i>p</i> < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index.</p><p><strong>Conclusions: </strong>The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041219","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":"Examining Prenylated Xanthones as Potential Inhibitors Against Ketohexokinase C Isoform for the Treatment of Fructose-Driven Metabolic Disorders: An Integrated Computational Approach.","authors":"Tilal Elsaman, Magdi Awadalla Mohamed","doi":"10.3390/ph18010126","DOIUrl":"10.3390/ph18010126","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Fructose-driven metabolic disorders, such as obesity, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes, are significant global health challenges. Ketohexokinase C (KHK-C), a key enzyme in fructose metabolism, is a promising therapeutic target. α-Mangostin, a naturally occurring prenylated xanthone, has been identified as an effective KHK-C inhibitor, prompting exploration of its analogs for enhanced efficacy. This study aimed to identify α-Mangostin analogs with improved inhibitory properties against KHK-C to address these disorders. <b>Methods:</b> A library of 1383 analogs was compiled from chemical databases and the literature. Molecular docking, binding free energy calculations, pharmacokinetic assessments, molecular dynamics simulations, and quantum mechani-cal analyses were used to screen and evaluate the compounds. α-Mangostin's binding affinity (37.34 kcal/mol) served as the benchmark. <b>Results:</b> Sixteen analogs demonstrated binding affinities superior to α-Mangostin (from -45.51 to -61.3 kcal/mol), LY-3522348 (-45.36 kcal/mol), and reported marine-derived inhibitors (from -22.74 to -51.83 kcal/mol). Hits <b>7</b>, <b>8</b>, <b>9</b>, <b>13</b>, and <b>15</b> not only surpassed these benchmarks in binding affinity, but also exhibited superior pharmacokinetic properties compared to α-Mangostin, LY-3522348, and marine-derived inhibitors, indicating strong in vivo potential. Among these, hit <b>8</b> emerged as the best performer, achieving a binding free energy of -61.30 kcal/mol, 100% predicted oral absorption, enhanced metabolic stability, and stable molecular dynamics. <b>Conclusions:</b> Hit <b>8</b> emerged as the most promising candidate due to its superior binding affinity, favorable pharmacokinetics, and stable interactions with KHK-C. These findings highlight its potential for treating fructose-driven metabolic disorders, warranting further experimental validation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041149","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":"Impact of Oseltamivir and Diabetes Development.","authors":"Bor-Show Tzang, Chih-Chen Tzang, Pei-Hua Chuang, I-Ying Kuo, Yu-Chun Pan, Pei-Hsun Wu, Tsai-Ching Hsu","doi":"10.3390/ph18010128","DOIUrl":"10.3390/ph18010128","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Influenza is a major global health challenge, causing thousands of deaths annually. Antiviral drugs, particularly oseltamivir, a neuraminidase inhibitor, have become essential therapeutic options due to their oral bioavailability and efficacy. Previous studies suggest a potential association between oseltamivir use and the onset of diabetes mellitus. However, further investigation is needed to establish a definitive link. <b>Methods</b>: This retrospective cohort study utilized data from the Taiwan National Health Insurance Research Database (NHIRD), including 1,631,968 patients (815,984 oseltamivir users) between 1 January 2009 and 28 December 2018. All statistical analyses were performed using SAS 9.4M8 software (SAS Institute Inc., Cary, NC, USA). <b>Results</b>: Cox proportional hazards regression and multivariate analyses revealed a statistically significant association between oseltamivir use and overall diabetes risk (HR = 1.027, <i>p</i> = 0.0186). While no significant association was observed for Type 1 diabetes (HR = 1.021; <i>p</i> = 0.06795), oseltamivir users showed a higher incidence of Type 2 diabetes (HR = 1.024; <i>p</i> < 0.05). Oseltamivir was also linked to increased risks of comorbidities, including dyslipidemia (HR = 1.295, <i>p</i> < 0.0001), chronic liver disease (HR = 1.446, <i>p</i> < 0.0001), hypertension (HR = 1.586, <i>p</i> < 0.0001), and obesity (HR = 2.949, <i>p</i> < 0.0001). <b>Conclusions</b>: Oseltamivir is associated with an increased risk of Type 2 diabetes but not Type 1, and related comorbidities.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041261","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":"Recent Advances in Peptide-Loaded PLGA Nanocarriers for Drug Delivery and Regenerative Medicine.","authors":"Hossein Omidian, Renae L Wilson, Ana M Castejon","doi":"10.3390/ph18010127","DOIUrl":"10.3390/ph18010127","url":null,"abstract":"<p><p>Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine. Innovations in polymer chemistry, surface functionalization, and advanced manufacturing techniques, such as microfluidics and electrospraying, have further enhanced the efficacy and scalability of these systems. This review highlights the key physicochemical properties, preparation strategies, and proven benefits of peptide-loaded PLGA systems, emphasizing their role in sustained drug release, immune activation, and tissue regeneration. Despite remarkable progress, challenges such as production scalability, cost, and regulatory hurdles remain.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041172","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":"Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide.","authors":"Leah Bush, Anthonia Okolie, Jenaye Robinson, Fatima Muili, Catherine A Opere, Sunny E Ohia, Ya Fatou Njie Mbye","doi":"10.3390/ph18010117","DOIUrl":"10.3390/ph18010117","url":null,"abstract":"<p><p>Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. <b>Purpose:</b> The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (H₂O₂)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (H₂S) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. <b>Methods:</b> Isolated neural retinas from cows were exposed to oxidative damage using H₂O₂ (100 µM) for 10 min. When used, tissues were pretreated with methanandamide (1 nM-100 nM) and 2-AG (1-10 µM) for 30 min before a 10 min treatment with H₂O₂ (100 µM). In some experiments, retinas were pretreated with inhibitors of the biosynthesis of H₂S [cystathionine β-synthase/cystathionine γ-lyase (CBS/CSE), aminooxyacetic acid, AOAA 30 µM, or 3-mercaptopyruvate sulfurtransferase (3MST), α-keto-butyric acid, KBA 1 mM] and the CB1-receptor antagonist, AM251 (100 nM) for 30 min before treatment with methanandamide (1 nM-100 µM). Enzyme immunoassay measurement of 8-epi PGF2α (8-isoprostane) levels was performed to assess lipid peroxidation in retinal tissues. <b>Results:</b> In the presence of H₂O₂ (100 µM), methanandamide (1 nM-100 µM) and 2-AG (1-10 µM) significantly (<i>p</i> < 0.001) blocked the H₂O₂-induced elevation in 8-isoprostane levels in the isolated bovine retina. In the presence of the CB1 antagonist AM251 (100 nM), the effect of methanandamide (1 nM) on the H₂O₂-induced 8-isoprostane production was significantly (<i>p</i> < 0.001) attenuated. While AOAA (30 µM) had no significant (<i>p</i> > 0.05) effect on the inhibition of H₂O₂-induced oxidative stress elicited by methanandamide, KBA (1 mM) reversed the neuroprotective action of methanandamide. <b>Conclusions:</b> The cannabinoids, methanandamide and 2-AG can prevent H₂O₂-induced oxidative stress in the isolated bovine retina. The neuroprotective actions of cannabinoids are partially dependent upon the activation of the CB1 receptors and endogenous production of H₂S via the 3-MST/CAT pathway.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040045","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}