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Exploring the Mechanism of Sempervirine Inhibiting Glioblastoma Invasion Based on Network Pharmacology and Bioinformatics. 基于网络药理学和生物信息学探索森佩尔韦林抑制胶质母细胞瘤侵袭的机制
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-02 DOI: 10.3390/ph17101318
Bingqiang Zhang, Wenyi Wang, Yu Song, Huixian Chen, Xinxin Lin, Jingjing Chen, Ying Chen, Jinfang Huang, Desen Li, Shuisheng Wu
{"title":"Exploring the Mechanism of Sempervirine Inhibiting Glioblastoma Invasion Based on Network Pharmacology and Bioinformatics.","authors":"Bingqiang Zhang, Wenyi Wang, Yu Song, Huixian Chen, Xinxin Lin, Jingjing Chen, Ying Chen, Jinfang Huang, Desen Li, Shuisheng Wu","doi":"10.3390/ph17101318","DOIUrl":"https://doi.org/10.3390/ph17101318","url":null,"abstract":"<p><p><b>Background</b>: Invasion is an important characteristic of the malignancy of glioblastoma (GBM) and a significant prognostic factor. Sempervirine (SPV), a yohimbine-type alkaloid, has been proven to inhibit GBM cells proliferation in previous research and found to have a potential effect in anti-invasion, but its mechanism of anti-invasion is still unknown. <b>Methods</b>: To explore its pharmacodynamics in inhibiting GBM cell invasion in this study, we combined network pharmacology and bioinformatics to comprehensive exploratory analysis of SPV and verified the mechanism in vitro. <b>Results</b>: Firstly, targets of SPV and invasion-related genes were collected from public databases. Moreover, GBM samples were obtained to analyze differentially expressed genes (DEGs) from The Cancer Genome Atlas (TCGA). Then, the relevant targets of SPV inhibiting GBM invasion (SIGI) were obtained through the intersection of the three gene sets. Further, GO and KEGG analysis showed that the targets of SIGI were heavily enriched in the AKT signaling pathway. Subsequently, based on the method of machine learning, a clinical prognostic model of the relevant targets of SIGI was constructed using GBM samples from TCGA and the Gene Expression Omnibus (GEO). A four-genes model (<i>DUSP6</i>, <i>BMP2</i>, <i>MMP2</i>, and <i>MMP13</i>) was successfully constructed, and Vina Scores of MMP2 and MMP13 in molecular docking were higher, which may be the main targets of SIGI. Then, the effect of SIGI was confirmed via functional experiments on invasion, migration, and adhesion assay, and the effect involved changes in the expressions of p-AKT, MMP2 and MMP13. Finally, combined with AKT activator (SC79) and inhibitor (MK2206), we further confirmed that SPV inhibits GBM invasion through AKT phosphorylation. <b>Conclusions</b>: This study provides valuable and an expected point of view into the regulation of AKT phosphorylation and inhibition of GBM invasion by SPV.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506306","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}
引用次数: 0
Arylpiperazine Derivatives and Cancer: A New Challenge in Medicinal Chemistry. 芳基哌嗪衍生物与癌症:药物化学的新挑战。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-02 DOI: 10.3390/ph17101320
Giorgia Andreozzi, Angela Corvino, Beatrice Severino, Elisa Magli, Elisa Perissutti, Francesco Frecentese, Vincenzo Santagada, Giuseppe Caliendo, Ferdinando Fiorino
{"title":"Arylpiperazine Derivatives and Cancer: A New Challenge in Medicinal Chemistry.","authors":"Giorgia Andreozzi, Angela Corvino, Beatrice Severino, Elisa Magli, Elisa Perissutti, Francesco Frecentese, Vincenzo Santagada, Giuseppe Caliendo, Ferdinando Fiorino","doi":"10.3390/ph17101320","DOIUrl":"https://doi.org/10.3390/ph17101320","url":null,"abstract":"<p><p><b>Background:</b> In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of arylpiperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. <b>Aim:</b> Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine compounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. <b>Conclusion:</b> This review, providing a careful analysis of different arylpiperazines and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506301","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}
引用次数: 0
Exploring Deep Eutectic Solvents as Pharmaceutical Excipients: Enhancing the Solubility of Ibuprofen and Mefenamic Acid. 探索作为药用辅料的深共晶溶剂:提高布洛芬和甲灭酸的溶解度。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-02 DOI: 10.3390/ph17101316
Mihaela-Alexandra Nica, Valentina Anuța, Cristian Andi Nicolae, Lăcrămioara Popa, Mihaela Violeta Ghica, Florentina-Iuliana Cocoș, Cristina-Elena Dinu-Pîrvu
{"title":"Exploring Deep Eutectic Solvents as Pharmaceutical Excipients: Enhancing the Solubility of Ibuprofen and Mefenamic Acid.","authors":"Mihaela-Alexandra Nica, Valentina Anuța, Cristian Andi Nicolae, Lăcrămioara Popa, Mihaela Violeta Ghica, Florentina-Iuliana Cocoș, Cristina-Elena Dinu-Pîrvu","doi":"10.3390/ph17101316","DOIUrl":"https://doi.org/10.3390/ph17101316","url":null,"abstract":"<p><p><b>Objectives</b>: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. <b>Methods</b>: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. <b>Results</b>: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812<sup>®</sup>N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. <b>Conclusions</b>: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506349","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}
引用次数: 0
Recent Advances in Ocular Drug Delivery: Insights into Lyotropic Liquid Crystals. 眼部给药的最新进展:对 Lyotropic 液晶的见解。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-02 DOI: 10.3390/ph17101315
Samer Adwan, Madeiha Qasmieh, Faisal Al-Akayleh, Ahmed Saad Abdulbari Ali Agha
{"title":"Recent Advances in Ocular Drug Delivery: Insights into Lyotropic Liquid Crystals.","authors":"Samer Adwan, Madeiha Qasmieh, Faisal Al-Akayleh, Ahmed Saad Abdulbari Ali Agha","doi":"10.3390/ph17101315","DOIUrl":"https://doi.org/10.3390/ph17101315","url":null,"abstract":"<p><p><b>Background/Objectives:</b> This review examines the evolution of lyotropic liquid crystals (LLCs) in ocular drug delivery, focusing on their ability to address the challenges associated with traditional ophthalmic formulations. This study aims to underscore the enhanced bioavailability, prolonged retention, and controlled release properties of LLCs that significantly improve therapeutic outcomes. <b>Methods:</b> This review synthesizes data from various studies on both bulk-forming LLCs and liquid crystal nanoparticles (LCNPs). It also considers advanced analytical techniques, including the use of machine learning and AI-driven predictive modeling, to forecast the phase behavior and molecular structuring of LLC systems. Emerging technologies in biosensing and real-time diagnostics are discussed to illustrate the broader applicability of LLCs in ocular health. <b>Results:</b> LLCs are identified as pivotal in promoting targeted drug delivery across different regions of the eye, with specific emphasis on the tailored optimization of LCNPs. This review highlights principal categories of LLCs used in ocular applications, each facilitating unique interactions with physiological systems to enhance drug efficacy and safety. Additionally, novel applications in biosensing demonstrate LLCs' capacity to improve diagnostic processes. <b>Conclusions:</b> Lyotropic liquid crystals offer transformative potential in ocular drug delivery by overcoming significant limitations of conventional delivery methods. The integration of predictive technologies and biosensing applications further enriches the utility of LLCs, indicating a promising future for their use in clinical settings. This review points to continued advancements and encourages further research in LLC technology to maximize its therapeutic benefits.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506392","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}
引用次数: 0
The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres. 炎症性肠病患者从阿达木单抗原研药非医疗转换后的疗效、安全性和持续性:来自两家三级医疗中心的实际经验。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-02 DOI: 10.3390/ph17101319
Teodora Spataru, Remus Popescu, Monica State, Mihai Pahomeanu, Bogdan Mateescu, Lucian Negreanu
{"title":"The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres.","authors":"Teodora Spataru, Remus Popescu, Monica State, Mihai Pahomeanu, Bogdan Mateescu, Lucian Negreanu","doi":"10.3390/ph17101319","DOIUrl":"https://doi.org/10.3390/ph17101319","url":null,"abstract":"<p><p>During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. <b>Materials and Methods:</b> This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. <b>Aims:</b> The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. <b>Results:</b> No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. <b>Conclusions</b>: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506425","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}
引用次数: 0
The Therapeutic Potential of Glucagon-like Peptide 1 Receptor Agonists in Traumatic Brain Injury. 胰高血糖素样肽 1 受体激动剂在创伤性脑损伤中的治疗潜力。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-01 DOI: 10.3390/ph17101313
Anja Harej Hrkać, Kristina Pilipović, Andrej Belančić, Lea Juretić, Dinko Vitezić, Jasenka Mršić-Pelčić
{"title":"The Therapeutic Potential of Glucagon-like Peptide 1 Receptor Agonists in Traumatic Brain Injury.","authors":"Anja Harej Hrkać, Kristina Pilipović, Andrej Belančić, Lea Juretić, Dinko Vitezić, Jasenka Mršić-Pelčić","doi":"10.3390/ph17101313","DOIUrl":"https://doi.org/10.3390/ph17101313","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), which is a global public health concern, can take various forms, from mild concussions to blast injuries, and each damage type has a particular mechanism of progression. However, TBI is a condition with complex pathophysiology and heterogenous clinical presentation, which makes it difficult to model for in vitro and in vivo studies and obtain relevant results that can easily be translated to the clinical setting. Accordingly, the pharmacological options for TBI management are still scarce. Since a wide spectrum of processes, such as glucose homeostasis, food intake, body temperature regulation, stress response, neuroprotection, and memory, were demonstrated to be modulated after delivering glucagon-like peptide 1 (GLP-1) or GLP-1 receptor agonists into the brain, we aimed to speculate on their potential role in TBI management by comprehensively overviewing the preclinical and clinical body of evidence. Based on promising preclinical data, GLP-1 receptor agonists hold the potential to extend beyond metabolic disorders and address unmet needs in neuroprotection and recovery after TBI, but also other types of central nervous system injuries such as the spinal cord injury or cerebral ischemia. This overview can lay the basis for tailoring new research hypotheses for future in vitro and in vivo models in TBI settings. However, large-scale clinical trials are crucial to confirm their safety and efficacy in these new therapeutic applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506432","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}
引用次数: 0
Neuroprotective Actions of Hydrogen Sulfide-Releasing Compounds in Isolated Bovine Retinae. 硫化氢释放化合物对离体牛视网膜的神经保护作用
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-01 DOI: 10.3390/ph17101311
Leah Bush, Jenaye Robinson, Anthonia Okolie, Fatima Muili, Catherine A Opere, Matthew Whiteman, Sunny E Ohia, Ya Fatou Njie Mbye
{"title":"Neuroprotective Actions of Hydrogen Sulfide-Releasing Compounds in Isolated Bovine Retinae.","authors":"Leah Bush, Jenaye Robinson, Anthonia Okolie, Fatima Muili, Catherine A Opere, Matthew Whiteman, Sunny E Ohia, Ya Fatou Njie Mbye","doi":"10.3390/ph17101311","DOIUrl":"https://doi.org/10.3390/ph17101311","url":null,"abstract":"<p><p><b>Background:</b> We have evidence that hydrogen sulfide (H<sub>2</sub>S)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since H<sub>2</sub>S has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of H<sub>2</sub>S-releasing compounds against hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced oxidative stress in an isolated bovine retina. <b>Materials and Methods:</b> The isolated neural retinae were pretreated with a substrate for H<sub>2</sub>S biosynthesis called L-cysteine, with the fast H<sub>2</sub>S-releasing compound sodium hydrosulfide, and with a mitochondrial-targeting H<sub>2</sub>S-releasing compound, AP123, for thirty minutes before a 30-min oxidative insult with H<sub>2</sub>O<sub>2</sub> (100 µM). Lipid peroxidation was assessed via an enzyme immunoassay by measuring the stable oxidative stress marker, 8-epi PGF2α (8-isoprostane), levels in the retinal tissues. To determine the role of endogenous H<sub>2</sub>S, studies were performed using the following biosynthesis enzyme inhibitors: aminooxyacetic acid (AOAA, 30 µM); a cystathione-β-synthase/cystathionine-γ-lyase (CBS/CSE) inhibitor, α-ketobutyric acid (KBA, 1 mM); and a 3-mercaptopyruvate-s-sulfurtransferase (3-MST) inhibitor, in the absence and presence of H<sub>2</sub>S-releasing compounds. <b>Results:</b> Exposure of the isolated retinas to H<sub>2</sub>O<sub>2</sub> produced a time-dependent (10-40 min) and concentration-dependent (30-300 µM) increase in the 8-isoprostane levels when compared to the untreated tissues. L-cysteine (10 nM-1 µM) and NaHS (30 -100 µM) significantly (<i>p</i> < 0.001; n = 12) prevented H<sub>2</sub>O<sub>2</sub>-induced oxidative damage in a concentration-dependent manner. Furthermore, AP123 (100 nM-1 µM) attenuated oxidative H<sub>2</sub>O<sub>2</sub> damage resulted in an approximated 60% reduction in 8-isoprostane levels compared to the tissues treated with H<sub>2</sub>O<sub>2</sub> alone. While AOAA (30 µM) and KBA (1 mM) did not affect the L-cysteine evoked attenuation of H<sub>2</sub>O<sub>2</sub>-induced oxidative stress, KBA reversed the antioxidant responses caused by AP123. <b>Conclusions:</b> In conclusion, various forms of H<sub>2</sub>S-releasing compounds and the substrate, L-cysteine, can prevent H<sub>2</sub>O<sub>2</sub>-induced lipid peroxidation in an isolated bovine retina.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506270","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}
引用次数: 0
Chemical Investigation and Regulation of Adipogenic Differentiation of Cultivated Moringa oleifera. 对栽培辣木脂肪分化的化学研究与调控
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-01 DOI: 10.3390/ph17101310
Duc Dat Le, Eunbin Kim, Thinhulinh Dang, Jiseok Lee, Choon Ho Shin, Jin Woo Park, Seul-Gi Lee, Jong Bae Seo, Mina Lee
{"title":"Chemical Investigation and Regulation of Adipogenic Differentiation of Cultivated <i>Moringa oleifera</i>.","authors":"Duc Dat Le, Eunbin Kim, Thinhulinh Dang, Jiseok Lee, Choon Ho Shin, Jin Woo Park, Seul-Gi Lee, Jong Bae Seo, Mina Lee","doi":"10.3390/ph17101310","DOIUrl":"https://doi.org/10.3390/ph17101310","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Moringa oleifera</i> is a matrix plant with the high potential to cure several diseases with its medicinal and ethnopharmacological value and nutraceutical properties. In this study, we investigated the chemical and biological properties of this plant cultivated in our local region. <b>Methods</b>: Leaves, roots, seeds, stem bark, and twigs of <i>oleifera</i> were extracted and evaluated bioactivities targeting intracellular lipid accumulation and adipocyte differentiation in 3T3-L1 preadipocytes, and UHPLC-ESI-Orbitrap-MS/MS-Based molecular networking guided isolation and dereplication of metabolites from these extracts. <b>Results</b>: Five extracts of different organs of <i>M</i>. <i>oleifera</i> significantly stimulated intracellular lipid accumulation and adipocyte differentiation in 3T3-L1 preadipocytes in a concentration-dependent manner. These extracts markedly increased the expression of genes related to adipogenesis and lipogenesis. Notably, these extracts promoted peroxisome proliferator-activated receptor γ (PPARγ) activity and the expression of its target genes, including phosphoenolpyruvate carboxykinase, fatty acid-binding protein 4, and perilipin-2. These adipogenic and lipogenic effects of Moringa extracts through the regulation of PPARγ activity suggests their potential efficacy in preventing or treating type 2 diabetes. Furthermore, chemical investigation revealed high contents of phytonutrients as rich sources of secondary metabolites including glycosides, flavones, fatty acids, phenolics, and other compounds. In addition, in silico studies on major components of these extracts revealed the bioavailability of major components through their binding affinity to respective proteins targeting adipocyte differentiation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506314","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}
引用次数: 0
Locally Injectable Chitosan/β-Glycerophosphate Hydrogel Doped with Triptolide-Human Serum Albumin Nanoparticles for Treating Rheumatoid Arthritis. 局部注射壳聚糖/β-甘油磷酸酯水凝胶掺杂曲托列汀-人血清白蛋白纳米粒子用于治疗类风湿性关节炎
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-01 DOI: 10.3390/ph17101312
Pu Yao, Zirui Tan, Bangbi Weng, Xiaowen Wang, Hongping Wang, Ge Yang, Fengjun Sun, Ying Zhao
{"title":"Locally Injectable Chitosan/β-Glycerophosphate Hydrogel Doped with Triptolide-Human Serum Albumin Nanoparticles for Treating Rheumatoid Arthritis.","authors":"Pu Yao, Zirui Tan, Bangbi Weng, Xiaowen Wang, Hongping Wang, Ge Yang, Fengjun Sun, Ying Zhao","doi":"10.3390/ph17101312","DOIUrl":"https://doi.org/10.3390/ph17101312","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) tends to occur in symmetrical joints and is always accompanied by synovial hyperplasia and cartilage damage. Triptolide (TP), an extract from <i>Tripterygium</i>, has anti-inflammatory and immunomodulatory properties and could be used in the treatment of RA. However, its poor water solubility and the multi-system lesions caused by the use of this substance limit its clinical application. Therefore, it would be of great significance to assemble a composite nanoparticle hydrogel and apply it to a collagen-induced arthritis (CIA) mouse model to investigate the therapeutic effect and biosafety of this compound.</p><p><strong>Method: </strong>TP@HSA nanoparticles (TP@HSA NPs) were fabricated with a self-assembly method; a thermosensitive hydrogel loaded with the TP@HSA NPs (TP@HSA NP hydrogel) was prepared by using chitosan and beta- glycerophosphate (β-GP) and was then intra-articularly injected into CIA mice. The changes in joint swelling were measured with a digital caliper, and inflammation and cartilage damage were evaluated by using hematoxylin and eosin (H&E) and safranin O-fast green (SO&FG) staining, respectively.</p><p><strong>Results: </strong>TP@HSA NPs with an average diameter of 112 ± 2 nm were successfully assembled, and their encapsulation efficiency and drug loading efficiency were 47.6 ± 1.5% and 10.6 ± 3.3%, respectively. The TP@HSA NP hydrogel had a gelation temperature of 30.5 ± 0.2 °C, which allows for its injection at low temperatures and its sol-gel transformation under physiological conditions within 2 min, making it a suitable drug depot. The TP@HSA NP hydrogel was intra-articularly injected into CIA mice; it released TP locally and exerted anti-inflammatory and immunomodulatory effects, alleviating synovial inflammation and cartilage damage effectively.</p><p><strong>Conclusions: </strong>We successfully fabricated a TP@HSA NP-loaded thermosensitive hydrogel with good biosafety, which can release TP slowly for the treatment of RA. Our study provides a basis for the development of TP-based innovative preparations and has good application prospects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506361","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}
引用次数: 0
Radiopharmaceuticals for Pancreatic Cancer: A Review of Current Approaches and Future Directions. 治疗胰腺癌的放射性药物:当前方法和未来方向综述》。
IF 4.3 3区 医学
Pharmaceuticals Pub Date : 2024-10-01 DOI: 10.3390/ph17101314
Sara Calistri, Giuseppe Ottaviano, Alberto Ubaldini
{"title":"Radiopharmaceuticals for Pancreatic Cancer: A Review of Current Approaches and Future Directions.","authors":"Sara Calistri, Giuseppe Ottaviano, Alberto Ubaldini","doi":"10.3390/ph17101314","DOIUrl":"https://doi.org/10.3390/ph17101314","url":null,"abstract":"<p><p>The poor prognosis of pancreatic cancer requires novel treatment options. This review examines the evolution of radiopharmaceuticals in the treatment of pancreatic cancer. Established strategies such as peptide receptor radionuclide therapy (PRRT) offer targeted and effective treatment, compared to conventional treatments. However, there are currently no radiopharmaceuticals approved for the treatment of pancreatic cancer in Europe, which requires further research and novel approaches. New radiopharmaceuticals including radiolabeled antibodies, peptides, and nanotechnological approaches are promising in addressing the challenges of pancreatic cancer therapy. These new agents may offer more specific targeting and potentially improve efficacy compared to traditional therapies. Further research is needed to optimize efficacy, address limitations, and explore the overall potential of these new strategies in the treatment of this aggressive and harmful pathology.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506390","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}
引用次数: 0
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