Pharmaceuticals最新文献

{"title":"Assessing Cardiovascular Target Attainment in Type 2 Diabetes Mellitus Patients in Tertiary Diabetes Center in Romania.","authors":"Teodor Salmen, Valeria-Anca Pietrosel, Delia Reurean-Pintilei, Mihaela Adela Iancu, Radu Cristian Cimpeanu, Ioana-Cristina Bica, Roxana-Ioana Dumitriu-Stan, Claudia-Gabriela Potcovaru, Bianca-Margareta Salmen, Camelia-Cristina Diaconu, Sanda Maria Cretoiu, Anca Pantea Stoian","doi":"10.3390/ph17091249","DOIUrl":"https://doi.org/10.3390/ph17091249","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) share a bidirectional link, and the innovative antidiabetic molecules GLP-1 Ras and SGLT-2is have proven cardiac and renal benefits, respectively. This study aimed to evaluate CV risk categories, along with lipid-lowering and antidiabetic treatments, in patients with T2DM from a real-life setting in Romania.</p><p><strong>Material and methods: </strong>A cross-sectional evaluation was conducted on 405 consecutively admitted patients with T2DM in an ambulatory setting, assessing them according to the 2019 ESC/EAS guidelines for moderate, high, and very high CV risk categories.</p><p><strong>Results: </strong>The average age of the group was 58 ± 9.96 years, with 38.5% being female. The mean HbA1C level was 7.2 ± 1.7%. Comorbidities included HBP in 88.1% of patients, with a mean SBP and DBP of 133.2 ± 13.7 mm Hg and 79.9 ± 9 mm Hg, respectively, and obesity in 66.41%, with a mean BMI of 33 ± 6.33 kg/m². The mean LDL-C levels varied by CV risk category: 90.1 ± 34.22 mg/dL in very high risk, 98.63 ± 33.26 mg/dL in high risk, and 105 ± 37.1 mg/dL in moderate risk. Prescribed treatments included metformin (100%), statins (77.5%), GLP-1 Ras (29.4%), and SGLT-2is (29.4%).</p><p><strong>Conclusions: </strong>In Romania, patients with T2DM often achieve glycemic control targets but fail to meet composite targets that include glycemic, BP, and lipid control. Additionally, few patients benefit from innovative glucose-lowering therapies with proven cardio-renal benefits or from statins.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352372","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 Anti-Vitiligo Effects of Feshurin In Vitro from <i>Ferula samarcandica</i> and the Mechanism of Action.","authors":"Mayire Nueraihemaiti, Zang Deng, Khamidulla Kamoldinov, Niu Chao, Maidina Habasi, Haji Akber Aisa","doi":"10.3390/ph17091252","DOIUrl":"https://doi.org/10.3390/ph17091252","url":null,"abstract":"<p><strong>Background: </strong>Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves <i>β</i>-catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. <i>Ferula</i> has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented.</p><p><strong>Methods: </strong>CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1.</p><p><strong>Results: </strong>The sesquiterpene coumarin feshurin was separated from <i>Ferula samarcandica</i>. Feshurin was shown to induce GSK-3<i>β</i> phosphorylation, resulting in the translocation of <i>β</i>-catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking.</p><p><strong>Conclusions: </strong>Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352450","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":"Comparative Assessment of Beeswax Alcohol and Coenzyme Q₁₀ (CoQ₁₀) to Prevent Liver Aging, Organ Damage, and Oxidative Stress in Hyperlipidemic Zebrafish Exposed to D-Galactose: A 12-Week Dietary Intervention.","authors":"Kyung-Hyun Cho, Ashutosh Bahuguna, Ji-Eun Kim, Yunki Lee, Sang Hyuk Lee","doi":"10.3390/ph17091250","DOIUrl":"https://doi.org/10.3390/ph17091250","url":null,"abstract":"<p><p>The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q₁₀ (CoQ₁₀) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ₁₀ and 1.0% CoQ₁₀ groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% (<i>p</i> < 0.001) and 41% (<i>p</i> < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ₁₀ group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% (<i>p</i> < 0.001) and 38% (<i>p</i> < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ₁₀ and 1.0% CoQ₁₀ groups showed similar TG levels as the control, suggesting that CoQ₁₀ supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ₁₀ group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ₁₀ group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352393","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":"Cancer Metastases to the Liver: Mechanisms of Tumor Cell Colonization.","authors":"Wiktoria Andryszkiewicz, Piotr Misiąg, Anna Karwowska, Zofia Resler, Aleksandra Wojno, Julita Kulbacka, Anna Szewczyk, Nina Rembiałkowska","doi":"10.3390/ph17091251","DOIUrl":"https://doi.org/10.3390/ph17091251","url":null,"abstract":"<p><p>The liver is one of the most common sites for metastasis, which involves the spread from primary tumors to surrounding organs and tissues in the human body. There are a few steps in cancer expansion: invasion, inflammatory processes allowing the hepatic niche to be created, adhesions to ECM, neovascularization, and secretion of enzymes. The spread of tumor cells depends on the microenvironment created by the contribution of many biomolecules, including proteolytic enzymes, cytokines, growth factors, and cell adhesion molecules that enable tumor cells to interact with the microenvironment. Moreover, the microenvironment plays a significant role in tumor growth and expansion. The secreted enzymes help cancer cells facilitate newly formed hepatic niches and promote migration and invasion. Our study discusses pharmacological methods used to prevent liver metastasis by targeting the tumor microenvironment and cancer cell colonization in the liver. We examine randomized studies focusing on median survival duration and median overall survival in patients administered placebo compared with those treated with bevacizumab, ramucirumab, regorafenib, and ziv-aflibercept in addition to current chemotherapy. We also include research on mice and their responses to these medications, which may suppress metastasis progression. Finally, we discuss the significance of non-pharmacological methods, including surgical procedures, radiotherapy, cryotherapy, radiofrequency ablation (RFA), and transarterial embolization (TAE). In conclusion, the given methods can successfully prevent metastases to the liver and prolong the median survival duration and median overall survival in patients suffering from cancer.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352380","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":"Real-Time Fluorescence Monitoring System for Optimal Light Dosage in Cancer Photoimmunotherapy.","authors":"Hideki Tanaka, Yoshikatsu Koga, Mayumi Sugahara, Hirobumi Fuchigami, Akihiro Ishikawa, Toru Yamaguchi, Akiko Banba, Takeshi Shinozaki, Kazuto Matsuura, Ryuichi Hayashi, Shingo Sakashita, Masahiro Yasunaga, Tomonori Yano","doi":"10.3390/ph17091246","DOIUrl":"https://doi.org/10.3390/ph17091246","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. <b>Methods</b>: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (-0.05%/s or -0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. <b>Results</b>: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. <b>Conclusions</b>: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336536","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 Silver Nanoparticles Functionalized with Spirulina Protein Extract on Rats.","authors":"Ludmila Rudi, Inga Zinicovscaia, Liliana Cepoi, Tatiana Chiriac, Dmitrii Grozdov, Alexandra Kravtsova","doi":"10.3390/ph17091247","DOIUrl":"https://doi.org/10.3390/ph17091247","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study investigates the biocompatibility and physiological impacts of silver nanoparticles (AgNPs) functionalized with Spirulina protein extract (SPE) on laboratory rats. The objective was to assess and compare the systemic distribution, organ accumulation, and changes in hematological and biochemical parameters between biofunctionalized and non-functionalized silver nanoparticles. <b>Methods:</b> AgNPs were functionalized with SPE. Adult Wistar rats were administered these nanoparticles to assess their distribution across various organs using ICP-MS analysis. Hematological and biochemical markers were measured to evaluate systemic effects. <b>Results</b>: Functionalized silver nanoparticles demonstrated preferential accumulation in the brain, liver, and testicles, with significant clearance observed post-administration. The persistence of AgNPs SPE in reproductive organs was established. Hematological analysis revealed moderate changes, suggesting mild immune activation. Biochemical tests indicated transient increases in liver enzymes, signaling reversible hepatic stress. <b>Conclusions</b>: The biofunctionalization of AgNPs with Spirulina protein extract modifies the nanoparticles' systemic behavior and organ distribution, enhancing their biocompatibility while inducing minimal physiological stress. These findings support the potential of Spirulina-based coatings to mitigate the toxicity and enhance the therapeutic efficacy of nanomedical agents.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352482","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":"Effects, Doses, and Applicability of Gestrinone in Estrogen-Dependent Conditions and Post-Menopausal Women.","authors":"Guilherme Renke, Mariana Antunes, Renato Sakata, Francisco Tostes","doi":"10.3390/ph17091248","DOIUrl":"https://doi.org/10.3390/ph17091248","url":null,"abstract":"<p><p>Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims to reevaluate the routes, doses, and applicability proposed for using gestrinone, including its use in new conditions such as menopause, lipedema, and sarcopenia. Here, we present the possible application of gestrinone as a long-acting therapeutic possibility through hormonal implants and the benefits and potential risks. Available evidence on the safety of doses and routes is limited. Gestrinone appears to be effective compared to other progestins and may have some advantages in the treatment of estrogen-dependent pathologies. Future research must evaluate gestrinone's long-term safety and potential therapeutic indications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352425","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":"Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies.","authors":"Cristina Ferreira Almeida, Andreia Palmeira, Maria João Valente, Georgina Correia-da-Silva, Anne Marie Vinggaard, Maria Emília Sousa, Natércia Teixeira, Cristina Amaral","doi":"10.3390/ph17091245","DOIUrl":"https://doi.org/10.3390/ph17091245","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands the development of novel therapeutic approaches. Due to key estrogen signaling, estrogen receptor-positive (ER⁺) breast cancer treatment has always been focused on aromatase inhibition and ER modulation. Lately, the effects of phytocannabinoids, mainly Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, <i>Cannabis sativa</i> contains more than 120 phytocannabinoids less researched and understood.</p><p><strong>Methods: </strong>Here, we evaluated, both in silico and in vitro, the ability of 129 phytocannabinoids to modulate important molecular targets in ER⁺ breast cancer: aromatase, ER, and androgen receptor (AR).</p><p><strong>Results: </strong>In silico results suggested that some cannabinoids may inhibit aromatase and act as ERα antagonists. Nine selected cannabinoids showed, in vitro, potential to act either as ER antagonists with inverse agonist properties, or as ER agonists. Moreover, these cannabinoids were considered as weak aromatase inhibitors and AR antagonists with inverse agonist action.</p><p><strong>Conclusions: </strong>Overall, we present, for the first time, a comprehensive analysis of the actions of the phytocannabinoids in targets of ER⁺ breast tumors, pointing out their therapeutic potential in cancer and in other diseases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352383","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":"Comprehensive Analysis of Characteristics of Cuproptosis-Related LncRNAs Associated with Prognosis of Lung Adenocarcinoma and Tumor Immune Microenvironment.","authors":"Feihong Chen, Xin Wen, Jiani Wu, Min Feng, Shicheng Feng","doi":"10.3390/ph17091244","DOIUrl":"https://doi.org/10.3390/ph17091244","url":null,"abstract":"<p><p>As a novel discovered mechanism of cell death, cuproptosis is copper-dependent and induces protein toxicity related to advanced tumors, disease prognosis, and human innate and adaptive immune response. However, it has not yet been fully established how the prognosis of lung adenocarcinoma (LUAD) is related to the immune microenvironment of cuproptosis-related lncRNAs using several bioinformatic techniques. In the study, 19 genes related to cuproptosis were collected. Subsequently, 783 lncRNAs related to the co-expression of cuproptosis were obtained. Moreover, the Cox model revealed and constructed four lncRNA (<i>AC012020.1</i>, <i>AC114763.1</i>, <i>AL161431.1</i>, <i>AC010260.1</i>) prognostic markers related to cuproptosis. Based on the median risk score (RS) values, patients were categorized into two groups: high risk and low risk. The Kaplan-Meier (KM) survival curve depicted a statistically significant overall survival (OS) rate among two groups. Principal component analysis (PCA) and receiver operator characteristic curve (ROC) proved that the model had promising ability in prognosis. The analysis of univariate and multivariate Cox regression revealed that RS served as an independent prognostic factor. Moreover, multivariate Cox regression was employed for the establishment of a nomogram of prognostic indicators. The tumor mutational burden (TMB) depicted a considerable difference between the two risk groups. The immunotherapy response of LUAD patients with high risk was improved compared to low risk patients. The study also revealed that drug sensitivity associated with LUAD was significantly linked to RS. The findings could be helpful to establish a good diagnosis, prognosis, and management regime for patients with LUAD.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352396","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":"Efficacy of Diterpene Polyalthic Acid Combined with Amphotericin B against <i>Leishmania amazonensis</i> In Vitro.","authors":"Ana Carolina Bolela Bovo Candido, Mariana Cintra Pagotti, Daiane Albino Dos Santos, Lucas Antonio de Lima Paula, Rodrigo Cássio Sola Veneziani, Jairo Kenupp Bastos, Sérgio Ricardo Ambrósio, Lizandra Guidi Magalhães","doi":"10.3390/ph17091243","DOIUrl":"https://doi.org/10.3390/ph17091243","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Leishmaniasis, a neglected disease caused by <i>Leishmania</i> spp. including <i>L. amazonensis</i>, urgently requires new treatments. Polyalthic acid (PA), a natural diterpene from <i>Copaifera</i> spp., has previously demonstrated significant antiparasitic potential. This study evaluated the leishmanicidal effects of polyalthic acid (PA), alone and with amphotericin B (AmpB), on <i>L. amazonensis</i> promastigote and amastigote forms. <b>Results:</b> PA showed significant activity against promastigotes, with 50% effective concentration (EC₅₀) values of 2.01 μM at 24 h and an EC₅₀ of 3.22 μM against amastigotes after 48 h. The PA and AmpB combination exhibited a synergistic effect on both forms without inducing cytotoxicity or hemolysis. Morphological changes in promastigotes, including vacuole formation and cell rounding, were more pronounced with the combination. <b>Conclusions:</b> These findings suggest that PA and AmpB together could form a promising new treatment strategy against <i>Leishmania</i> infections, offering enhanced efficacy without added toxicity.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352437","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}