Pharmaceuticals最新文献

{"title":"Antioxidant Peptides Derived from Woody Oil Resources: Mechanisms of Redox Protection and Emerging Therapeutic Opportunities.","authors":"Jia Tu, Jie Peng, Li Wen, Changzhu Li, Zhihong Xiao, Ying Wu, Zhou Xu, Yuxi Hu, Yan Zhong, Yongjun Miao, Jingjing Xiao, Sisi Liu","doi":"10.3390/ph18060842","DOIUrl":"10.3390/ph18060842","url":null,"abstract":"<p><p>Antioxidant peptides derived from woody oil resource by-products exhibit strong free radical scavenging abilities and offer potential applications in functional foods, nutraceuticals, and cosmetics. This review summarizes the latest advances in preparation technologies, including enzymatic hydrolysis, microbial fermentation, chemical synthesis, recombinant expression, and molecular imprinting, each with distinct advantages in yield, selectivity, and scalability. The structure-activity relationships of antioxidant peptides are explored with respect to amino acid composition, molecular weight, and 3D conformation, which collectively determine their bioactivity and stability. Additionally, emerging delivery systems-such as nanoliposomes, microencapsulation, and cell-penetrating peptides-are discussed for their role in enhancing peptide stability, absorption, and targeted release. Mechanistic studies reveal that antioxidant peptides from woody oil resources act through network pharmacology, engaging core signaling pathways, including Nrf2/ARE, PI3K/Akt, AMPK, and JAK/STAT, to regulate oxidative stress, mitochondrial health, and inflammation. Preliminary safety data from in vitro, animal, and early clinical studies suggest low toxicity and favorable tolerability. The integration of omics technologies, molecular docking, and bioinformatics is accelerating the mechanism-driven design and functional validation of peptides. In conclusion, antioxidant peptides derived from woody oil resources represent a sustainable, multifunctional, and scalable solution for improving human health and promoting a circular bioeconomy. Future research should focus on structural optimization, delivery enhancement, and clinical validation to facilitate their industrial translation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507659","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":"Natural Nanoparticles for Drug Delivery: Proteomic Insights and Anticancer Potential of Doxorubicin-Loaded Avocado Exosomes.","authors":"Dina Salem, Shaimaa Abdel-Ghany, Eman Mohamed, Nada F Alahmady, Amany Alqosaibi, Ibtesam S Al-Dhuayan, Mashal Meshal Alnamshan, Rebekka Arneth, Borros Arneth, Hussein Sabit","doi":"10.3390/ph18060844","DOIUrl":"10.3390/ph18060844","url":null,"abstract":"<p><p><b>Background</b>: Exosomes have recently attracted significant attention for their potential in drug delivery. Plant-derived exosomes, in particular, may serve as direct anticancer agents due to their unique characteristics, including immunogenicity, biocompatibility, safety, cell-free nature, and nanoscale structure. <b>Methods</b>: This study characterizes <i>Persea americana</i> (avocado)-derived exosomes, exploring their anticancer properties, proteomic profile, and therapeutic potential. <b>Results</b>: Isolated exosomes exhibited a diameter of 99.58 ± 5.09 nm (non-loaded) and 151.2 ± 6.36 nm (doxorubicin (DOX)-loaded), with zeta potentials of -17 mV and -28 mV, respectively. Proteomic analysis identified 47 proteins, including conserved exosome markers (GAPDH, tubulin) and stress-response proteins (defensin, endochitinase). Functional enrichment revealed roles in photosynthesis, glycolysis, ATP synthesis, and transmembrane transport, supported by protein-protein interaction networks highlighting energy metabolism and cellular trafficking. DOX encapsulation efficiency was 18%, with sustained release (44.4% at 24 h). In vitro assays demonstrated reduced viability in breast cancer (MCF-7, T47D, 4T1) and endothelial (C166) cells, enhanced synergistically by DOX (Av+DOX). Gene expression analysis revealed cell-specific modulation: Av+DOX upregulated <i>TP53</i> and <i>STAT</i> in T47D but suppressed both in 4T1/C166, suggesting context-dependent mechanisms. <b>Conclusions</b>: These findings underscore avocado exosomes as promising nanovehicles for drug delivery, combining biocompatibility, metabolic functionality, and tunable cytotoxicity. Their plant-derived origin offers a scalable, low-cost alternative to mammalian exosomes, with potential applications in oncology and targeted therapy. Further optimization of loading efficiency and in vivo validation are warranted to advance translational prospects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507714","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 Taste Disorders in Rats with Type 2 Diabetes Mellitus by Increasing the Number of Taste Buds and the Expression of Signaling Molecules in Taste Transduction Pathways.","authors":"Zhen-Ran Hu, Xiang-Ke Li, Guo-Jun Fei, Ming-Yu Wang, Meng-Juan Luo, Xin-Xin Zeng, Liang Wang, Ze-Min Yang","doi":"10.3390/ph18060838","DOIUrl":"10.3390/ph18060838","url":null,"abstract":"<p><p><b>Background:</b> Taste disorders in patients with type 2 diabetes mellitus (T2DM) have a negative impact on their quality of life and glycemic control, and treatment options are limited. Buzhong yiqi formula (BZYQF) improves T2DM symptoms but its effects on T2DM-induced taste disorders have not been sufficiently studied. <b>Methods</b>: Molecular docking was utilized to evaluate binding activity between the compounds in BZYQF and the sweet taste receptors (STRs). T2DM was induced in rats through the administration of high-fat diet and streptozotocin, and the rats were then treated with BZYQF for 8 weeks. Daily indicators and serum biochemical factors were monitored. Taste preferences for sweet, bitter, salty, and sour solutions were assessed using a two-bottle test. The morphology of lingual papillae and the numbers of taste buds were examined using HE staining. A high-glucose (HG) model of taste bud organoids was established to measure sucrose-evoked ATP release. The expression of signaling molecules in the sweet taste receptors (STRs) pathway was determined via RT-qPCR, Western blot, and immunofluorescence in lingual papillae and organoids. <b>Results</b>: A total of 508 compounds in BZYQF indicated good binding activity to T1R2, T1R3 or heterodimers of T1R2/T1R3, and 60 compounds had good binding activity to all three forms of STRs. BZYQF alleviated T2DM symptoms and improved taste perception for maltose (10 mM, 50 mM), quinine (0.03 mM, 0.1 mM), and citric acid (1 mM) solutions. BZYQF improved the morphological structure of lingual papillae and increased taste bud numbers in T2DM rats. BZYQF enhanced ATP release responses to sucrose solution in the taste bud organoids of the HG model. Gene expression determination showed that BZYQF upregulated the expression of signaling molecules in the STRs pathway (T1R2, T1R3, IP3R, α-gustducin, TRPM5) in the lingual papillae of the T2DM rats and in the taste bud organoids of the HG model. <b>Conclusions</b>: BZYQF alleviates T2DM-induced taste disorders by increasing the numbers of taste buds and upregulating STR signaling molecules, in which various compounds, especially flavonoids, exhibit a synergistic effect.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507671","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":"New Insights into the Anticancer Effects and Toxicogenomic Safety of Two β-Lapachone Derivatives.","authors":"José Rivaldo De Lima, Alexandre José Da Silva Góes, Elizabeth Fernanda De Oliveira Borba, Meykson Alexandre da Silva, Rodrigo Ribeiro Alves Caiana, Maria do Desterro Rodrigues, Mariza Severina De Lima Silva, Cristiano Aparecido Chagas, Blandine Baratte, Thomas Robert, Stéphane Bach, Isabelle Ourliac-Garnier, Pascal Marchand, Teresinha Gonçalves Da Silva","doi":"10.3390/ph18060837","DOIUrl":"10.3390/ph18060837","url":null,"abstract":"<p><p><b>Background/Objectives:</b> β-Lapachone (β-lap) is an <i>o</i>-naphthoquinone with potent antitumor activity. However, its clinical application is hindered by poor solubility and toxicity. Thiosemicarbazone derivatives of β-lap (BV3 and BV5) have demonstrated enhanced selectivity and anticancer efficacy in leukemia cells. Therefore, this study aimed to evaluate the therapeutic potential of these derivatives in solid tumors. Furthermore, the mechanism of tumor cell death, the involvement of protein kinase inhibition, and the toxicogenetic safety of BV3 and BV5 were investigated. <b>Methods</b>: The cytotoxic effects of BV3 and BV5 were assessed in cancer cell lines and a non-cancerous cell line. The compounds were most effective against HeLa (human cervical adenocarcinoma) cells. For that reason, this type of cell was chosen to study how the compounds might cause cell death, using flow cytometry. Kinase inhibition assays were conducted in vitro and in silico, followed by genotoxicity assessments to determine toxicogenetic safety. <b>Results</b>: BV3 and BV5 derivatives significantly inhibited cancer cell proliferation after 72 h, with IC₅₀ values ranging from 2.8 to 36.9 µM. BV3 demonstrated superior selectivity (selectivity index: 15.6) when compared to β-lap (selectivity index: 1.9) in HeLa cells. Morphological changes and flow cytometry analysis revealed features of apoptosis and/or necrosis in HeLa cells treated with the compounds BV3 and BV5. Furthermore, among the kinases tested, BV3 and BV5 were more effective in inhibiting the activity of the protein kinases JAK3 and GSK3β. This result was also confirmed by the in silico studies. Additionally, genotoxicity assays indicated an overall favorable toxicogenetic safety profile; however, BV5 exhibited potential genotoxicity at high concentrations. <b>Conclusions</b>: The findings underscore the anticancer potential of BV3 and BV5 in solid tumors and highlight their mechanism of action, which involves protein kinases. The findings also show that the drugs are selective and relatively safe.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507727","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":"Khellin Mitigates Cisplatin-Induced Renal Injury by Targeting Oxidative Stress, Inflammation, and Apoptosis: Integration of Network Pharmacology, Molecular Docking, and Preclinical Validation.","authors":"Zeina W Sharawi, Shimaa A Abass, Manal A Zubair, Rabab A Hegazy, Foad A Farrag, Abdelrahman Hamdi, Mohammed A El-Magd, Abdullah A Elgazar","doi":"10.3390/ph18060836","DOIUrl":"10.3390/ph18060836","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The present study aimed to evaluate the nephroprotective role of Khellin (Khe) against cisplatin (CDDP)-mediated nephrotoxicity in rats. <b>Methods</b>: We assessed oxidative stress markers (MDA, CAT, SOD, GPx, and iNOs), inflammatory markers (TNFα, IL6, IL10, and MCP1), apoptotic markers (Bax and Bcl2), and the renal damage marker (Kim1). Network pharmacology and molecular docking studies were performed. In vitro, Khe effects were tested on normal kidney cells (Vero) and liver cancer cells (HepG2) treated with CDDP. <b>Results</b>: Network pharmacology and docking suggested Khe's activity primarily affects oxidative stress and inflammatory pathways, notably through MAPK14 and PI3K downregulation. In vitro, Khe reduced CDDP's cytotoxicity in Vero cells while maintaining anti-proliferative effects on HepG2 cells. In vivo, CDDP significantly increased serum creatinine, urea, Kim1, oxidative stress markers (MDA and iNOS), and inflammatory markers (TNFα, IL6, and MCP1) while decreasing antioxidant markers (SOD, GPx, CAT, and SOD3) and anti-inflammatory cytokine (IL10) levels. Khe treatment dose-dependently attenuated these changes, with the 100 mg/kg dose showing the most significant renoprotection. Histopathological analysis confirmed improved renal tissue integrity in Khe-treated groups. <b>Conclusions</b>: This study demonstrates that Khe exerts significant nephroprotective effects against CDDP-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis while improving renal function and structure. These findings suggest Khe as a promising therapeutic candidate for preventing CDDP-related kidney injury.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507694","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":"<i>Rhodococcus rhodochrous</i> IEGM 1362 Immobilized in Macroporous PVA Cryogel as an Effective Biocatalyst for the Production of Bioactive (-)-Isopulegol Compounds.","authors":"Polina Y Maltseva, Natalia A Plotnitskaya, Alexandra A Chudinova, Irina V Ilyina, Konstantin P Volcho, Nariman F Salakhutdinov, Irina B Ivshina","doi":"10.3390/ph18060839","DOIUrl":"10.3390/ph18060839","url":null,"abstract":"<p><p><b>Background</b>: This study explored the biotransformation of (-)-isopulegol using immobilized cells of <i>Rhodococcus rhodochrous</i> IEGM 1362 to optimize the production of new bioactive compounds. <b>Methods</b>: An efficient biocatalyst based on <i>R</i>. <i>rhodochrous</i> IEGM 1362 cells immobilized in a macroporous polyvinyl alcohol (PVA) cryogel matrix was developed for the production of bioactive derivatives of (-)-isopulegol. The biological characteristics of the immobilized cells were investigated using scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy methods. <b>Results</b>: The use of the biocatalyst increased the overall yield of target products from 54% with free cells to 87% with immobilized cells in a single cycle. Major derivatives identified included (1<i>R</i>,2<i>S</i>,5<i>R</i>)-5-(hydroxymethyl)-2-(prop-1-en-2-yl)cyclohexanol and (1<i>R</i>,3<i>R</i>,4<i>S</i>)-3-hydroxy-4-(prop-1-en-2-yl)cyclohexanecarboxylic acid, both exhibiting potential pharmacological activity. The biocatalyst retained functional activity toward monoterpenoid over 13 exploitation cycles, meeting industrial biotechnology requirements. Immobilized cells were characterized by the absence of endogenous reserve inclusions (in particular lipids) and a high intracellular iron content. <b>Conclusions</b>: The developed immobilized biocatalyst is promising for scaling up the production of biologically active compounds.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507642","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 Effect of Metformin on Pituitary Function in Postmenopausal Women with Subclinical Hypothyroidism and Macroprolactinemia: A Single-Center Prospective Case-Control Study.","authors":"Robert Krysiak, Witold Szkróbka, Karolina Kowalcze, Bogusław Okopień","doi":"10.3390/ph18060834","DOIUrl":"10.3390/ph18060834","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Metformin inhibits secretory function of overactive thyrotrophs, gonadotrophs, and lactotrophs. The clinical significance of an excess of high-molecular-weight prolactin (macroprolactinemia) remains unclear. The aim of the current study was to investigate for the first time whether macroprolactinemia determines the pituitary effects of this drug. <b>Methods:</b> This single-center prospective case-control study included two groups of postmenopausal women with subclinical hypothyroidism, who were matched for age, insulin sensitivity, and plasma concentrations of gonadotropins and TSH. Group A enrolled women with normal prolactin status, while group B included women with macroprolactinemia. Owing to concomitant type 2 diabetes or prediabetes, all the participants received metformin for six months. The outcomes of interest included glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA-IR), plasma prolactin (total and monomeric), macroprolactin, other pituitary hormones (FSH, LH, TSH, and ACTH), and peripheral hormones (estradiol, free thyroid hormones, and IGF-1). <b>Results:</b> Before metformin treatment, the study groups differed only in concentrations of total prolactin and macroprolactin. Metformin decreased FSH and TSH and tended to decrease LH only in group A, and the strength of this effect showed correlations with the baseline levels of these hormones, the degree of improvement in insulin sensitivity, and the macroprolactin content (only in group B). The decrease in fasting glucose, glycated hemoglobin, and HOMA-IR was more pronounced in group A than group B. There were no differences between the pretreatment and posttreatment values of total prolactin, monomeric prolactin, macroprolactin, ACTH, estradiol, free thyroid hormones, and IGF-1. <b>Conclusions:</b> The obtained results suggest that macroprolactinemia may counteract the pituitary effects of metformin.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507792","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":"Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib.","authors":"Ya-Dong Yang, Chen Zhao, Liang-Peng Li, Yi-Xin Lv, Bei-Bei Yang, Xin Li, Ru Wang, Li Li","doi":"10.3390/ph18060833","DOIUrl":"10.3390/ph18060833","url":null,"abstract":"<p><p><b>Background/Objective</b>: Avapritinib is an orally bioavailable tyrosine kinase inhibitor and was approved by the FDA in 2020 for gastrointestinal stromal tumor treatments. Although avapritinib is known to be chiral, its stereochemistry was initially established randomly. This study aims to develop a definitive method for determining avapritinib's absolute configuration and propose a universal methodology for stereochemical characterization of flexible chiral drugs. <b>Methods</b>: The absolute configuration of avapritinib was determined through an integrated approach combining chiral resolution, chiroptical spectroscopy and synthetic validation. Enantiomeric separation was achieved via chiral liquid chromatography, followed by comprehensive chiroptical characterization including electronic circular dichroism (ECD), specific optical rotation and optical rotatory dispersion. Conformational analysis and density functional theory (DFT) calculations correlated experimental spectra with theoretical predictions, facilitating definitive configurational assignment. The stereochemical determination were further verified through ECD derivatization and chemical synthesis. Finally, the enantiomers' kinase inhibition profiles against c-KIT D816V were quantitatively assessed. <b>Results</b>: Two enantiomers of avapritinib were resolved via chiral HPLC and a Chiralpak IG column. Through combined experimental ECD spectra and time-dependent DFT calculations employing the core extraction method, the <i>levo</i>-isomer was unambiguously determined as <i>S</i> configuration. This stereochemical assignment was confirmed by <i>p</i>-cyanobenzaldehyde derivatization and de novo synthesis. Biological evaluation revealed (<i>S</i>)-(-)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (<i>R</i>)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. <b>Conclusions</b>: This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507603","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":"Amphiphilic Bioactives of Freshwater Aquatic Plants <i>Nelumbo nucifera</i> (Indian Lotus) and <i>Lemna</i> sp. with Antioxidant, Anti-Inflammatory and Antithrombotic Activities: In Vitro Study.","authors":"Marina Seferli, Melina Lefkaki, Vasileios Manousakis, Anna Ofrydopoulou, Katie Shiels, Sushanta Kumar Saha, Grigorios Krey, Nikolaos Kamidis, Nikolaos Stamatis, Chryssa Anastasiadou, Alexandros Tsoupras","doi":"10.3390/ph18060835","DOIUrl":"10.3390/ph18060835","url":null,"abstract":"<p><p><b>Background-Objectives:</b> Chronic diseases linked to inflammation, such as cardiovascular disease (CVD) and cancer, continue to pose major public health challenges due to their high mortality rates. There is growing interest in natural bioactive compounds, particularly those derived from plants, as potential therapeutic or preventive agents due to their low toxicity profiles. This study aimed to explore two freshwater plants-<i>Nelumbo nucifera</i> (Indian lotus) and <i>Lemna</i> sp.-as potential sources of bioactive compounds with antioxidant, anti-inflammatory, and antithrombotic properties. While <i>N. nucifera</i> has established but incompletely characterized biofunctional properties, <i>Lemna</i> sp. remains largely unexplored in this context. <b>Methods:</b> Amphiphilic extracts from both plant species were analyzed for phenolic and lipid constituents, including unsaturated fatty acids, polar lipids, and carotenoids. Antioxidant capacity was evaluated using DPPH, ABTS, and FRAP assays. Anti-inflammatory and antithrombotic activities were assessed via platelet aggregation assays using PAF and ADP agonists. Structural characterization was performed using <b>Fourier transform infrared spectroscopy</b> (FT-IR) and liquid chromatography-mass spectroscopy (LC-MS) to support structure-activity relationship (SAR) analysis. <b>Results:</b> Extracts, particularly from <i>Lemna</i> sp., showed potent antiplatelet activity against PAF and ADP. LC-MS revealed the presence of polar lipids rich in monounsaturated and omega-3 polyunsaturated fatty acids, with a favorable omega-6/omega-3 ratio, especially in <i>Lemna</i> sp., correlating with strong anti-inflammatory potential. High levels of total phenolics and carotenoids were observed, aligning with substantial antioxidant capacity in both species. <b>Conclusions:</b> These findings suggest that <i>N. nucifera</i> and <i>Lemna</i> sp. are promising sources of bioactive compounds with potential applications in functional foods, cosmetics, and pharmaceuticals targeting inflammation- and thrombosis-related chronic diseases. Further studies are warranted to confirm their safety and efficacy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507655","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":"Effect of Tegoprazan on Tacrolimus and Mycophenolate Levels in Kidney Transplant Recipients: A Randomized Controlled Study Using a Smart Trial Platform.","authors":"Seong-Wook Lee, You Hyun Jeon, Jeong-Hoon Lim, Jung Ju Seo, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Yong-Lim Kim, Jang-Hee Cho","doi":"10.3390/ph18060830","DOIUrl":"10.3390/ph18060830","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Potassium-competitive acid blockers (P-CABs) offer rapid gastric acid inhibition and lower toxicity compared to proton pump inhibitors (PPIs). This study investigates the drug-drug interaction between P-CABs and immunosuppressants tacrolimus and mycophenolate in kidney transplant recipients (KTRs). <b>Methods</b>: Sixty-two KTRs were randomized to receive either 50 mg of tegoprazan or 20 mg of pantoprazole. Patients were monitored using a smart clinical trial platform incorporating remote monitoring and safety management systems, which tracked drug adherence and vital signs. General and gastrointestinal (GI) symptoms were surveyed via a self-developed app on patients' phones. Trough levels of tacrolimus and mycophenolate were measured every 4 weeks over 12 weeks. <b>Results</b>: Medication adherence was 100% in both groups. A total of 13,726 biometric data points and 5031 questionnaire responses were collected, with 5704 feedback messages and 56 video visits conducted. At 12 weeks, the mean trough levels of tacrolimus and mycophenolate were similar between the tegoprazan and pantoprazole groups (5.5 ± 1.6 vs. 5.8 ± 2.0 ng/mL, <i>p</i> = 0.50 and 2.7 ± 1.4 vs. 2.6 ± 1.4 µg/mL, <i>p</i> = 0.57, respectively). The intragroup difference in trough levels from baseline to week 12 was not significant in either group. GI symptoms scores, vital signs, and allograft function remained stable and comparable between groups. <b>Conclusions</b>: Tegoprazan does not alter the blood trough levels of tacrolimus and mycophenolate during the 12-week follow-up in KTRs and has a similar impact on GI symptoms as pantoprazole. This study confirms the feasibility and safety of using a smart clinical trial system with remote monitoring for randomized trials.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507715","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}