Pharmaceuticals最新文献

{"title":"Investigation on Human Carbonic Anhydrase IX and XII Inhibitory Activity and A549 Antiproliferative Activity of a New Class of Coumarinamides.","authors":"Davide Moi, Simone Carradori, Marialucia Gallorini, Noemi Mencarelli, Alberto Deplano, Andrea Angeli, Serena Vittorio, Claudiu T Supuran, Valentina Onnis","doi":"10.3390/ph18030372","DOIUrl":"10.3390/ph18030372","url":null,"abstract":"<p><p><b>Background</b>-Aggressive solid tumors are commonly characterized by both basic intracellular pH and acidic extracellular pH, which increase cell survival and proliferation. As carbonic anhydrases IX/XII are involved in this pH regulation, their inhibition is an appealing approach in cancer therapy, avoiding cancer cell survival and proliferation. Substituted coumarins are selective non-classical CA IX and CA XII inhibitors. <b>Methods</b>-In this study, new 7-hydroxycoumarinamides were synthesized and assayed for CA inhibition and antiproliferative activity. <b>Results</b>-All of the coumarinamides showed human CA IX and CA XII selective inhibition over the off-target CA I and CA II isoforms. Coumarin acts as a suicide inhibitor because its heterocyclic ring can be hydrolyzed by CA esterase activity to give the corresponding 2-hydroxycinnamic acid derivative which blocks the entrance of the active site. The 2-hydroxycinnamic acid derivatives deriving from the most potent and selective coumarinamides were docked into CA IX and XII to better understand the activity and selectivity against the two CA isoforms. The most active coumarinamides also produced a decrease of A549 cell proliferation and were able to arrest cells at the G1/S checkpoint. <b>Conclusions</b>-These results may open new perspectives for developing coumarin-based CA IX/XII inhibitors.</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/PMC11944513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720639","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":"Exosomes in Ovarian Cancer: Towards Precision Oncology.","authors":"Maria Grazia Perrone, Silvana Filieri, Amalia Azzariti, Domenico Armenise, Olga Maria Baldelli, Anselma Liturri, Anna Maria Sardanelli, Savina Ferorelli, Morena Miciaccia, Antonio Scilimati","doi":"10.3390/ph18030371","DOIUrl":"10.3390/ph18030371","url":null,"abstract":"<p><p><b>Background</b>: Identification of targetable biomarkers to improve early disease detection and overall patient outcomes is becoming an urgent need in clinical oncology. Ovarian cancer (OC) has one of the highest mortality rates among gynecological cancers. It is asymptomatic and almost always diagnosed at an advanced stage (III or IV), leading to a 5-year survival rate of approximately 35%. <b>Methods</b>: Current therapeutic approaches for OC are very limited and mainly consist of cytoreductive surgery and cisplatin plus taxane-based chemotherapy. No gender and tumor specific biomarkers are known. Exosomes, lipid bilayer vesicles of endocytic origin secreted by most cell types, represent sources of information for their involvement in the onset and progression of many diseases. Hence, research on exosome contents as tools and targets in precise oncology therapy provides knowledge essential to improving diagnosis and prognosis of the disease. <b>Results</b>: This review attempts to give an overview of how exosomes are implicated in ovarian carcinoma pathogenesis to trigger further cancer exosome-based investigations aimed at developing ovarian cancer fine-tuning diagnostic methodologies. <b>Conclusions</b>: It is essential to investigate exosome-based cancer drugs to advance understanding, improve treatment plans, create personalized strategies, ensure safety, and speed up clinical translation to increase patients' overall survival and quality of life. Papers published in PubMed and Web of Science databases in the last five years (2020-2024) were used as a bibliographic source.</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/PMC11946531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721066","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":"Beyond Conventional Antifungals: Combating Resistance Through Novel Therapeutic Pathways.","authors":"Helal F Hetta, Tameem Melhem, Hashim M Aljohani, Ayman Salama, Rehab Ahmed, Hassabelrasoul Elfadil, Fawaz E Alanazi, Yasmin N Ramadan, Basem Battah, Michelangelo Rottura, Matthew Gavino Donadu","doi":"10.3390/ph18030364","DOIUrl":"10.3390/ph18030364","url":null,"abstract":"<p><p>The rising burden of fungal infections presents a significant challenge to global healthcare, particularly with increasing antifungal resistance limiting treatment efficacy. Early detection and timely intervention remain critical, yet fungal pathogens employ diverse mechanisms to evade host immunity and develop resistance, undermining existing therapeutic options. Limited antifungal options and rising resistance necessitate novel treatment strategies. This review provides a comprehensive overview of conventional antifungal agents, their mechanisms of action, and emerging resistance pathways. Furthermore, it highlights recently approved and investigational antifungal compounds while evaluating innovative approaches such as nanotechnology, drug repurposing, and immunotherapy. Addressing antifungal resistance requires a multifaceted strategy that integrates novel therapeutics, enhanced diagnostic tools, and future research efforts to develop sustainable and effective treatment solutions.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721115","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":"Seaweed in the Diet as a Source of Bioactive Metabolites and a Potential Natural Immunity Booster: A Comprehensive Review.","authors":"Amiya Kumar Mandal, Sudhamayee Parida, Akshaya Kumar Behera, Siba Prasad Adhikary, Andrey A Lukatkin, Alexander S Lukatkin, Mrutyunjay Jena","doi":"10.3390/ph18030367","DOIUrl":"10.3390/ph18030367","url":null,"abstract":"<p><p>Seaweed plays an essential role in the survival of marine life, provides habitats and helps in nutrient recycling. It is rich in valuable nutritious compounds such as pigments, proteins, polysaccharides, minerals, vitamins, omega-rich oils, secondary metabolites, fibers and sterols. Pigments like fucoxanthin and astaxanthin and polysaccharides like laminarin, fucoidan, galactan and ulvan possess immune-modulatory and immune-enhancing properties. Moreover, they show antioxidative, antidiabetic, anticancer, anti-inflammatory, antiproliferative, anti-obesity, antimicrobial, anticoagulation and anti-aging properties and can prevent diseases such as Alzheimer's and Parkinson's and cardiovascular diseases. Though seaweed is frequently consumed by Eastern Asian countries like China, Japan, and Korea and has gained the attention of Western countries in recent years due to its nutritional properties, its consumption on a global scale is very limited because of a lack of awareness. Thus, to incorporate seaweed into the global diet and to make it familiar as a functional food, issues such as large-scale cultivation, processing, consumer acceptance and the development of seaweed-based food products need to be addressed. This review is intended to give a brief overview of the present status of seaweed, its nutritional value and its bioactive metabolites as functional foods for human health and diseases owing to its immunity-boosting potential. Further, seaweed as a source of sustainable food and its prospects along with its issues are discussed in this review.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721104","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":"Correction: Khan et al. Anti-Oxidative and Anti-Apoptotic Oligosaccharides from <i>Pichia pastoris</i>-Fermented Cress Polysaccharides Ameliorate Chromium-Induced Liver Toxicity. <i>Pharmaceuticals</i> 2024, <i>17</i>, 958.","authors":"Imdad Ullah Khan, Aqsa Aqsa, Yusra Jamil, Naveed Khan, Amjad Iqbal, Sajid Ali, Muhammad Hamayun, Abdulwahed Fahad Alrefaei, Turki Kh Faraj, Bokyung Lee, Ayaz Ahmad","doi":"10.3390/ph18030365","DOIUrl":"10.3390/ph18030365","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721144","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":"Antimicrobial and Antiherpetic Properties of Nanoencapsulated <i>Hypericum perforatum</i> Extract.","authors":"Yoana Sotirova, Nadezhda Ivanova, Neli Ermenlieva, Neli Vilhelmova-Ilieva, Lora Simeonova, Miroslav Metodiev, Viliana Gugleva, Velichka Andonova","doi":"10.3390/ph18030366","DOIUrl":"10.3390/ph18030366","url":null,"abstract":"<p><p><b>Background/Objectives:</b> This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich <i>Hypericum perforatum</i> L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. <b>Methods</b>: Two established NLC specimens, comprising glyceryl behenate and almond oil or borage oil, and their extract-loaded counterparts (HP-NLCs) were utilized. Their minimal bactericidal/fungicidal concentrations (MBC; MFC) were investigated against <i>Escherichia coli</i> ATCC 25922, <i>Staphylococcus aureus</i> ATCC 25923, <i>Pseudomonas aeruginosa</i> ATCC 10145, <i>Klebsiella pneumoniae</i> ATCC 10031, and <i>Candida albicans</i> ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. <b>Results</b>: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against <i>S. aureus</i> (MBC 6.3 mg/mL), <i>K. pneumoniae</i> (MBC 97.7 µg/mL), and <i>C. albicans</i> (MFC < 48.8 µg/mL), unlike the almond oil-containing sample (HP-NLC1), which showed only weak inhibition of the fungal growth. HP-NLC2 was found to be less cytotoxic and to suppress HSV-1 replication slightly more than HP-NLC1, but generally, the effects were weak. Neither the empty lipid nanoparticles nor the HP extract-loaded carriers expressed activity against <i>E. coli</i>, <i>P. aeruginosa</i>, the HSV-1 extracellular virions, or viral adhesion. <b>Conclusions</b>: It could be concluded that both HP-NLC samples revealed only minor antiherpetic potential of the hyperforin-rich extract, but HP-NLC2 demonstrated significant antibacterial and antimycotic activity. Therefore, the latter was featured as a more convenient HP-carrier system for nano-designed dermal pharmaceutical formulations. Such a thorough investigation of hyperforin-determined anti-HSV-1 effects and antibacterial and antimycotic properties, being the first of its kind, contributes to the fundamental knowledge of HP and reveals new perspectives for the utilization, limitations, and therapeutic designation of its non-polar components.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721074","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":"Usage Frequency and Ecotoxicity of Skin Depigmenting Agents.","authors":"Sandra Mota, Liliana Rego, Emília Sousa, Maria Teresa Cruz, Isabel Martins de Almeida","doi":"10.3390/ph18030368","DOIUrl":"10.3390/ph18030368","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Depigmenting cosmetic products are a fast-growing segment of the health products market, driven by consumer demand to address skin hyperpigmentation. Simultaneously, interest in products with a reduced environmental impact is increasing. However, the potential environmental risks, especially in aquatic ecosystems, of depigmenting products remain unexplored. This study assesses the usage frequency of skin depigmenting agents in cosmetic products and compiles data on the biodegradability and acute aquatic toxicity of the most prevalent compounds. <b>Methods:</b> A market analysis of Portuguese pharmacies and parapharmacies in 2022 identified prevalent depigmenting agents. Scientific evidence on their biodegradability and acute aquatic toxicity was compiled, and when data was unavailable, in silico predictions were conducted. <b>Results:</b> The study identified the ten most-used depigmenting agents in cosmetic products, including hydroxy/keto acids, as well as vitamin C and derivatives, with a usage frequency surpassing 50%. While most were naturally derived and showed low environmental risk, synthetic and highly lipophilic depigmenting agents found in 35 of 70 products (ascorbyl tetraisopalmitate/tetrahexyldecyl ascorbate and resorcinol derivatives) showed a higher potential for environmental hazard. <b>Conclusions:</b> The findings underscore the need for further research on the presence of these cosmetic ingredients in aquatic ecosystems and a reassessment of regulatory frameworks concerning their environmental impact. Mitigation strategies should emphasize biodegradable alternatives, renewable sources, and molecular modifications to reduce toxicity while maintaining depigmenting efficacy and skin safety. This study provides original insights into commonly used depigmenting agents in the health products market and their chemical structures, offering valuable opportunities for innovation in chemical/pharmaceutical industries.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721209","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":"Cortical Potentiation in Chronic Neuropathic Pain and the Future Treatment.","authors":"Shun Hao, Shen Lin, Wucheng Tao, Min Zhuo","doi":"10.3390/ph18030363","DOIUrl":"10.3390/ph18030363","url":null,"abstract":"<p><p>Pain, or the ability to feel pain and express the unpleasantness caused by peripheral injuries, are functions of the central nervous system. From peripheral sensory nerve terminals to certain cortical regions of the brain, activation of related neural networks underlies the sensory process. Recently, our knowledge of pain has been increasing dramatically, due to the advancement of scientific approaches. We no longer see the brain as a random matrix for pain but, rather, we are able to identify the step-by-step selective signaling proteins, neurons, and networks that preferentially contribute to the process of chronic pain and its related negative emotions, like anxiety and fear. However, there is still lacking the selective and effective drugs and methods for the treatment of chronic pain clinically. While first-line drugs for acute pain and mental diseases are also applied for the clinical management of chronic pain, their prolonged usage always causes serious side effects. In this short review, we will update and summarize the recent progress in this field and mainly focus on the roles of neural networks and synaptic mechanisms in chronic neuropathic pain. Furthermore, potential drug targets (such as plasticity-related signaling molecules, ionic channels, cytokines, and neuropeptides) and methods for the management of chronic neuropathic pain will be discussed as well. We hope this review can provide new, valuable insight into the treatment of chronic neuropathic pain.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721146","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":"Synergistic Efficacy of Policosanol (Raydel^®) and Banaba Leaf Extract to Treat Hyperglycemia and Dyslipidemia in Streptozotocin-Induced Diabetic and Hyperlipidemic Zebrafish (<i>Danio rerio</i>): Protection of Liver and Kidney with Enhanced Tissue Regeneration.","authors":"Kyung-Hyun Cho, Sang Hyuk Lee, Yunki Lee, Ashutosh Bahuguna, Ji-Eun Kim","doi":"10.3390/ph18030362","DOIUrl":"10.3390/ph18030362","url":null,"abstract":"<p><p><b>Background:</b> The efficacy of banaba leaf extract was tested against carboxymethyllysine (CML)-induced toxicity in embryos and adult zebrafish. Additionally, the individual and combined effects of banaba (BNB) and policosanol (PCO) were analyzed to alleviate dyslipidemia, hyperglycemia, and associated effects in streptozotocin (STZ)-induced hyperlipidemic diabetic zebrafish. <b>Methodology:</b> The high cholesterol diet (HCD, final 4%, <i>w</i>/<i>w</i>)-fed zebrafish were injected with STZ to develop diabetes and were subsequently fed with either HCD or HCD+BNB (final 0.1% <i>w</i>/<i>w</i>) or HCD+PCO (final 0.1% <i>w</i>/<i>w</i>) or HCD+BNB+PCO (each final 0.1%, <i>w</i>/<i>w</i>) each for 14 days. The zebrafish tail fin was amputated to assess tissue regeneration, while the organs and blood were collected for histological and biochemical analysis. <b>Results:</b> Severely compromised embryo survivability and developmental defects were noticed in the CML-injected group that significantly improved following BNB exposure. Similarly, CML-induced acute paralysis and mortality of adult zebrafish were effectively mitigated by the treatment with BNB. In the hyperlipidemic diabetic zebrafish, both BNB and PCO supplementation displayed the hypoglycemic effect; however, a remarkable reduction (<i>p</i> < 0.05) in blood glucose levels was observed in the BNB+PCO group, around 14% and 16% less than the BNB group and PCO group, respectively. Likewise, higher tail fin regeneration was noticed in response to BNB+PCO supplementation. Both BNB and PCO have a substantial counter-effect against HCD+STZ-induced dyslipidemia. However, the combined supplementation (BNB+PCO) displayed a significantly better effect than that of BNB and PCO alone to alleviate total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). The most impressive impact of BNB+PCO was noticed in the elevation of high-density lipoprotein cholesterol (HDL-C), which was ~1.5 times higher than the HDL-C level in response to BNB and PCO. Also, BNB+PCO effectively reduced the malondialdehyde (MDA) and elevated the plasma sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Histological analyses revealed a significant effect of BNB+PCO in preventing inflammatory infiltration, fatty liver changes, and interleukin-6 production. Similarly, a notably better effect of BNB+PCO compared to their individual effect was noticed in preventing kidney damage and mitigation of ROS generation, apoptosis, and cellular senescence. <b>Conclusions:</b> The finding establishes the substantial effect of BNB and PCO in countering hyperglycemia, dyslipidemia, and associated disorders, which synergistically improved following the combined supplementation with BNB+PCO.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721220","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 Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats.","authors":"Hanan Abdelmawgoud Atia, Hemat A Elariny, Marwa H Abdallah, Amany M Khalifa, Remon S Estfanous, Maaly A Abd Elmaaboud, Ahmed M Kabel","doi":"10.3390/ph18030358","DOIUrl":"10.3390/ph18030358","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Methotrexate is a folate antagonist that has proven efficacy as an anticancer and immunomodulatory agent. However, the possible incidence of overt hepatotoxicity represents a challenge for its clinical use. Up till now, no single remedy has been considered an effective solution to this important adverse effect. Perindopril is an angiotensin-converting enzyme inhibitor that is widely used for the treatment of hypertension. Due to the involvement of the renin-angiotensin system in the pathogenesis of methotrexate-elicited hepatotoxicity, investigating the efficacy of perindopril in this condition may be of particular interest. The current work aimed at an evaluation of the potential effects of perindopril in a rat model of methotrexate-induced hepatotoxicity and tried to precisely determine the molecular mechanisms that may represent the basis of these effects. <b>Methods:</b> In a model of methotrexate-elicited hepatotoxicity in male Wistar rats, the effects of different doses of perindopril were evaluated at the level of the biochemical measurements and the morphological examination. <b>Results:</b> Oral administration of perindopril to methotrexate-injected rats exhibited a dose-dependent significant improvement in daily food intake; the restoration of the functions of hepatocytes; the potentiation of antioxidant defense mechanisms; the abrogation of the different signaling pathways involved in liver inflammation, apoptosis, and fibrosis; and an enhancement in AMPK/mTOR-driven autophagy when compared to animals that received only a methotrexate injection. These events were reflected in the morphological appearance of the different studied groups. <b>Conclusions:</b> This study presents perindopril as a promising remedy for mitigation of the hepatotoxic effects that occur as a consequence of treatment with methotrexate.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721128","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}