Drug Design, Development and Therapy最新文献

{"title":"Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway.","authors":"Tianwei Dong, Jinlian Li, Xinfang Liang, Wang Wang, Meichi Chen, Guangyuan Yang, Dongmei Wu","doi":"10.2147/DDDT.S497323","DOIUrl":"10.2147/DDDT.S497323","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is a chemotherapeutic agent widely used for cancer treatment and has non-negligible cardiotoxicity. Some previous studies have reported that cannabidiol (CBD) has cardioprotective effects. In this study, we evaluated the protective effects of CBD against DOX-induced cardiomyocyte injury, and explored the downstream molecular mechanism.</p><p><strong>Methods and materials: </strong>GSE193861, containing healthy myocardial tissues and myocardial tissues with DOX-induced injury, was analyzed to screen for the involved proteins and pathways. Molecular docking was performed to identify candidate drugs. After H9c2 cells were treated with DOX and CBD, their viability, oxidative stress, and apoptosis were assessed. After YAP depletion, the role of the Hippo pathway in CBD function was investigated. C57BL/6 mice were treated with DOX to establish an in vivo model, and CBD and verteporfin (VP) were used to treat the mice. Histological analyses and immunofluorescence were used to evaluate myocardial tissue injury, and apoptosis and oxidative stress of the myocardial tissues were also analyzed. Western blotting was used to investigate the regulatory effects of CBD on the Hippo and apoptosis-related pathways.</p><p><strong>Results: </strong>Bioinformatic analysis suggested that the Hippo pathway was a crucial pathway involved in DOX-induced myocardial injury. Molecular docking showed that CBD targeted multiple regulators of the Hippo pathway. CBD showed cardioprotective effects against DOX-induced myocardial injury both in vitro and in vivo and regulated Hippo pathway activity in cardiomyocytes. After inactivation of the Hippo pathway by YAP knockdown or VP intervention, the protective effects of CBD were reversed.</p><p><strong>Conclusion: </strong>For the first time, we revealed that CBD is likely to reduce DOX-induced myocardial injury by regulating the Hippo signaling pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"569-583"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Delivery of Dacarbazine and miRNA 34a Combinations to Synergistically Improve Malignant Melanoma Treatments.","authors":"Baoyue Ding, Mingjuan Li, Jie Zhang, Xiaojuan Zhang, Huan Gao, Jianqing Gao, Chunyan Shen, Yan Zhou, Fanzhu Li, Ailin Liu","doi":"10.2147/DDDT.S497888","DOIUrl":"10.2147/DDDT.S497888","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of malignant melanoma (MM) has risen over the past three decades, and despite advancements in treatment, there is still a need to improve treatment modalities. This study developed a promising strategy for tumor-targeted co-delivery of Dacarbazine (DTIC) and miRNA 34a-loaded PHRD micelles (Co-PHRD) for combination treatment of MM.</p><p><strong>Methods: </strong>To construct the dual drug-loaded delivery system Co-PHRD, poly (L-arginine)-poly (L-histidine)-polylactic acid (PLA) was employed as a building block. In this system, poly (L-arginine) and PLA function as hydrophilic and hydrophobic blocks, respectively, which self-assemble into micelles in aqueous solution. Poly(L-arginine) and poly(L-histidine) are efficiently taken up by cells and perform efficient gene condensation, which facilitate the release of encapsulated miRNA 34a into the cytoplasm. Due to its lipophilic properties, PLA can effectively encapsulate DTIC. The polypeptide aptamer DR5-TAT (D21) was used as a targeting ligand. The properties of Co-PHRD and its in vitro release behaviour were characterized. Additionally, the synergetic effects of DTIC and miRNA 34a in melanoma therapy were investigated in vitro and in vivo.</p><p><strong>Results: </strong>Compared to DTIC treatment alone, Co-PHRD treatment exhibited 1.84-fold greater cytotoxicity in A375 cells, demonstrating that miRNA 34a enhanced the efficacy of DTIC. The particle size of Co-PHRD at an N/P ratio of 10 was 164.1 ± 4.5 nm, and the zeta potential of Co-PHRD was 27.3 ± 1.38 mV. The flow cytometry and CLSM results revealed both DTIC and miRNA 34a were avidly taken up by A375 cells at 1 h and 4 h in PHRD. In addition, in vivo results indicated that Co-PHRD micelles can significantly inhibit tumor growth without causing significant damage to major organs.</p><p><strong>Conclusion: </strong>Co-delivery of DTIC and miRNA 34a via polypeptide micelles showed synergistic effects against MM, offering a new strategy for gene and chemotherapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"553-568"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Food on the Pharmacokinetics and Safety of HA121-28 Tablet, a Novel Multi-Targeting Tyrosine Kinase Inhibitor, in Healthy Chinese Subjects: A Phase I Clinical Trial.","authors":"Yixian Liu, Xiaoyu Li, Mengyu Zhang, Yuchun Men, Ying Wang, Xiaohong Zhu, Li Zheng","doi":"10.2147/DDDT.S484310","DOIUrl":"10.2147/DDDT.S484310","url":null,"abstract":"<p><strong>Purpose: </strong>HA121-28, a novel multi-targeting tyrosine kinase inhibitor, has dual efficacy against tumor growth and neovascularization. The objectives of this study were to assess the effect of high-fat and high-calorie food on the pharmacokinetic (PK) profile and safety of HA121-28 tablet in healthy subjects.</p><p><strong>Patients and methods: </strong>A single-dose, randomized, open-label, two-period, crossover-designed phase I clinical trial was conducted. Subjects received 200 mg HA121-28 in the fasted state or with high-fat and high-calorie breakfast. The effects of high-fat and high-calorie food on the PK profile and safety of HA121-28 were evaluated by using noncompartmental analysis and whole-process safety assessment.</p><p><strong>Results: </strong>Twenty subjects were successfully completed the trial. The geometric mean ratios (GMRs) for the peak concentration in plasma (C_max), area under the curve from zero to the time point (AUC_last), and area under the curve from zero to infinite (AUC_inf) postprandially versus fasted were 108.45% (98.51% - 119.40%), 105.23% (100.25% - 110.47%), and 104.14% (97.41% - 111.34%), respectively. The majority of reported adverse events were graded as either level 1 or 2 in severity and recovered spontaneously without any interventions.</p><p><strong>Conclusion: </strong>The exposure of HA121-28 was not significantly affected by the high-fat and high-calorie food. The clinical application of HA121-28 tablet can be recommended for use in both fasted and postprandial states.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"515-524"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Lupeol on Intestinal Anastomosis After Experimental Intestinal Ischemia-Reperfusion Injury in Rats.","authors":"Cem Kaya, Alparslan Kapisiz, Sibel Eryilmaz, Ramazan Karabulut, Zafer Turkyilmaz, Mehmet Arda Inan, Gizem Yaz Aydin, Mert Alperen Celik, Kaan Sonmez","doi":"10.2147/DDDT.S501289","DOIUrl":"10.2147/DDDT.S501289","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia/reperfusion (I/R) injury can occur in a wide variety of diseases and surgeries. If necessary, the blood flow should be restored, including re-anastomosis by removing the intestines with impaired circulation. In this process, anastomotic strength is as important as inflammatory responses and oxidative stress. Therefore, we conducted the study to investigate the effects of lupeol on intestinal ischemia-reperfusion injury, not only biochemically and histopathologically but also on anastomotic strength and miRNAs.</p><p><strong>Methods: </strong>Female rats were randomly divided into six groups. While only laparotomy was performed in the control group (Group C), anastomosis was performed in the sham group (Group S). In the other groups, the superior mesenteric artery was clamped for 45 minutes. In the groups I/R¹ and L¹, the intestine was transected, and end-to-end anastomosis was performed at the 1st hour of reperfusion. In the groups I/R²⁴ and L²⁴, this procedure was performed at the 24th hour of reperfusion. In addition, lupeol treatment was given before reperfusion and for the following 4 days in the groups L¹ and L²⁴. All rats, except the control group, bursting pressure was measured on the 5th day of anastomosis, and then all rats including the control group were sacrificed. TNF-α, IL-6 levels in blood samples and MDA, GSH, caspase-3, miR-29b-3p, miR-34a-5p, miR-495-3p levels in intestinal tissues were measured, and intestinal histopathology was also examined.</p><p><strong>Results: </strong>Lupeol treatment, which was statistically significant in some parameters, demonstrated positive effects by decreasing TNF, IL-6, MDA, caspase-3, histopathological damage levels and increasing GSH and bursting pressure. In addition, lupeol decreased miR-34a-5p expression and increased miR-29b-3p and miR-495-3p expression.</p><p><strong>Conclusion: </strong>Lupeol protected the intestines from I/R damage with its antioxidant and anti-inflammatory effects. Besides, it reduced the histopathological damage and increased the anastomotic strength. Additionally, miR-29b-3p, miR-34a-5p, miR-495-3p expressions were altered by lupeol.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"479-490"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress of SGLT2 Inhibitors in Cancer Treatment.","authors":"Xiaoyong Miao, Jianing Zhang, Weiyan Huang, Yifei Wang, Aixia Jin, Jianping Cao, Zhenzhen Zhao","doi":"10.2147/DDDT.S485755","DOIUrl":"10.2147/DDDT.S485755","url":null,"abstract":"<p><p>Sodium glucose co-transporter 2 (SGLT2) inhibitors represent a novel class of hypoglycemic drugs that have emerged in recent years. These inhibitors function primarily by blocking the reabsorption of glucose in the kidneys, specifically targeting the SGLT2 proteins in the proximal convoluted tubules. This inhibition results in the reduction of blood glucose levels through increased glucose excretion in the urine. Recent studies have identified SGLT2 expression in various cancer types, suggesting that SGLT2 inhibition can potentially suppress tumor growth. This article provides a comprehensive review of the role of SGLT2 in tumorigenesis and tumor progression, and explores the underlying mechanisms and potential therapeutic applications of SGLT2 inhibitors as anticancer agents.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"505-514"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Effect Sevoflurane-Based Anesthesia and Propofol-Based Anesthesia on the Early Postoperative Renal Function of Living Kidney Transplant Donors: A Randomized Controlled Trial.","authors":"Jianyue Cai, Fang Kang, Mingming Han, Xiang Huang, Wenlong Yan, Fuzhen Wan, Juan Li","doi":"10.2147/DDDT.S486393","DOIUrl":"10.2147/DDDT.S486393","url":null,"abstract":"<p><strong>Purpose: </strong>Living kidney transplantation is a common treatment for end-stage renal disease. The impact of anaesthetics on postoperative biomarkers of renal injury in living kidney transplant donors is not well understood.</p><p><strong>Patients and methods: </strong>70 transplant donors who underwent kidney extraction were randomly assigned to following two groups: sevoflurane (S group) and propofol (P group). Urine and blood were collected before induction and 1, 2, 6 days after operation. Kidney injury marker-1 (KIM-1), interleukin-18 (IL-18) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were measured by enzyme-linked immunosorbent assay. Record the cystatin C, glomerular filtration rate, urine output during perioperative period.</p><p><strong>Results: </strong>There were both increases in biomarkers of kidney injury before and 1, 2 and 6 days after the anaesthetic surgery in donors, However, no statistical differences in KIM-1 (P (0.42 pg/mL (95% CI 0.21 to 0.63 pg/mL)) vs S (0.26 pg/mL (95% CI 0.02 to 0.49 pg/mL)), -0.16 pg/mL (95% CI -0.48 to 0.16 pg/mL)), IL-18 (P (178.54 pg/mL (95% CI 110.15 to 24693 pg/mL)) vs S (175.86 pg/mL (95% CI 100.35 to 251.38 pg/mL)), -2.68 pg/mL (95% CI -105.61 to 100.25 pg/mL)), and TIMP-2 (P (12.88 ng/mL (95% CI 8.69 to 17.07 ng/mL)) vs S (14.85 ng/mL (95% CI 10.23 to 19.46 ng/mL)), 1.97 ng/mL (95% CI -4.30 to 8.23 ng/mL)) concentration changes between the two types of anaesthesia.</p><p><strong>Conclusion: </strong>There was no difference between sevoflurane and propofol anaesthesia on postoperative changes in biomarkers of renal injury in living kidney transplant donors.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"491-503"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy Between Intravenous Paracetamol and Intravenous Fentanyl for Propofol Deep Sedation in Colonoscopy: A Randomized Controlled Trial.","authors":"Thanitthi Thiparporn, Wilaiporn Supan, Somchai Amornyotin","doi":"10.2147/DDDT.S479084","DOIUrl":"10.2147/DDDT.S479084","url":null,"abstract":"<p><strong>Introduction: </strong>Sedation practices for colonoscopy indeed vary widely around the globe. Due to a lack of data on intravenous paracetamol, we aimed to investigate the clinical efficacy of intravenous paracetamol compared to intravenous fentanyl under propofol deep sedation for colonoscopy.</p><p><strong>Methods: </strong>A total of 225 patients who underwent colonoscopy at Siriraj Hospital were randomly assigned to two groups. All patients underwent deep sedation with propofol and received intravenous (iv) paracetamol (group P, n = 113) or iv fentanyl (group F, n = 112). All patients received a premedication of 0.02-0.03 mg/kg of midazolam intravenously. Fifteen to thirty minutes before the procedure, patients in group P were administered 1000 mg of iv paracetamol, while those in group F received 0.001 mg/kg of iv fentanyl. All patients were oxygenated with 100% O₂ via a nasal cannula, and deep sedated with titrated intravenous propofol. The primary outcome measure was the success rate of colonoscopy. The colonoscope reaching the ileocecal valve was an important marker for a successful colonoscopy. Secondary outcome measures included endoscopist and patient satisfaction, patient tolerance, ease of the procedure, and sedation-related complications during and immediately after the procedure.</p><p><strong>Results: </strong>All colonoscopies were successfully completed. There were no significant differences in patient characteristics, duration of the procedure, endoscopist and patient satisfaction, patient tolerance, or ease of the procedure between the two groups. However, group F experienced significantly higher rates of upper airway obstruction and oxygen desaturation during the procedure compared to group P. No serious complications were observed in either group.</p><p><strong>Conclusion: </strong>Intravenous paracetamol with propofol deep sedation in adult patients is non-inferior to intravenous fentanyl for successful colonoscopy completion. Sedation-related complications were relatively lower in the propofol deep sedation with iv paracetamol group compared to the propofol deep sedation with iv fentanyl group.</p><p><strong>Registration: </strong>This trial was registered with the Thai Clinical Trial Registry (TCTR 20190321002).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"471-478"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Oral Diseases: Mechanisms and Therapeutic Applications.","authors":"Qiandai Miao, Shaoqing Li, Weijia Lyu, Jianxia Zhang, Yan Han","doi":"10.2147/DDDT.S505355","DOIUrl":"10.2147/DDDT.S505355","url":null,"abstract":"<p><p>Exosomes, small extracellular vesicles secreted by various cells, play crucial roles in the pathogenesis and treatment of oral diseases. Recent studies have highlighted their involvement in orthodontics, periodontitis, oral squamous cell carcinoma (OSCC), and hand, foot, and mouth disease (HFMD). Exosomes have a positive effect on the inflammatory environment of the oral cavity, remodeling and regeneration of oral tissues, and offer promising therapeutic options for bone and periodontal tissue restoration. In OSCC tumor-derived exosomes promote cancer progression through cell proliferation, migration, invasion, and angiogenesis, and serve as potential biomarkers for early diagnosis and prognosis. Additionally, engineered exosomes constructed specifically based on exosome properties hold great promise for targeted drug delivery and regenerative therapies such as bone regeneration in orthodontics and periodontal healing. With continued research, exosomes hold great potential for improving diagnosis and treatment in oral diseases, advancing personalized and regenerative therapies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"457-469"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice With Mitoxantrone-Induced Cardiotoxicity.","authors":"Qing Zhang, Deshuai Liang, Chengfang Zhang, Ling Ye, Ping Sun, Hongli Zhu, Yongqin Zhao, Yuewen Li, Yun Guan, Haiguo Zhang","doi":"10.2147/DDDT.S479682","DOIUrl":"10.2147/DDDT.S479682","url":null,"abstract":"<p><strong>Purpose: </strong>Mitoxantrone (MTX) is largely restricted in clinical usage due to its significant cardiotoxicity. Multiple studies have shown that an imbalance in the gut-heart axis plays an important role in the development of cardiovascular disease (CVD). We aim to explore the possible correlations between gut microbiota (GM) compositions and cardiometabolic (CM) disorder in MTX-triggered cardiotoxicity mice.</p><p><strong>Methods: </strong>MTX cumulative dose of 6 mg/kg was administered to healthy Kunming male mice to trigger cardiotoxicity, with 1 mg/kg twice weekly for a duration of 3 weeks. Plasma CK-MB and LDH levels were determined, and the heart tissue histopathology was assessed, followed by utilizing an integrated liquid chromatography-mass spectrometry (LC-MS)-based heart metabolomics study alongside the 16S ribosomal RNA (rRNA) sequencing method to assess MTX impact on GM and CM profiles in mice, establishing associations between GM and CM profiles through the Pearson correlation coefficient calculation.</p><p><strong>Results: </strong>MTX caused CK-MB and LDH level elevations and cardiotoxicity in our mouse model. MTX primarily affected the processes of protein digestion and absorption, mineral absorption, membrane transport, production of aminoacyl-transfer RNA (tRNA), metabolism of nucleotides, lipids, and amino acids, as well as autophagy. Additionally, MTX increased <i>Romboutsia, Enterococcus</i>, and <i>Turicibacter</i> abundances and lowered <i>norank_f__Muribaculaceae, Alistipes, Odoribacter, norank_f__Lachnospiraceae, norank_f__Ruminococcaceae, norank_f__Oscillospiraceae, unclassified_f__Ruminococcaceae, NK4A214_group, Colidextribacter, norank_f__norank_o__Clostridia_vadinBB60_group, Rikenella</i>, and <i>Anaerotruncus</i> abundances. The correlation analyses showcased variations in the abundance of diverse flora, such as <i>Romboutsia, Enterococcus, Turicibacter, and norank</i>_<i>f__Muribaculaceae</i>, which were related to MTX-induced cardiac injury.</p><p><strong>Conclusion: </strong>Our study supports the claim that MTX provokes cardiotoxicity by modifying CM and GM profiles. Our results offer new possibilities for controlling MTX-triggered cardiotoxicity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"439-455"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Metabolic Changes in Mice Exposed to Corilagin Based on GC-MS Analysis.","authors":"Biao Xu, Changshui Wang, Xiaodong Zhu, Li Zhu, Guangkui Han, Changmeng Cui","doi":"10.2147/DDDT.S482510","DOIUrl":"10.2147/DDDT.S482510","url":null,"abstract":"<p><strong>Background: </strong>Corilagin is widely distributed in various medicinal plants. In recent years, numerous pharmacological activities of Corilagin have been reported, including anti-inflammatory, antiviral, hepatoprotective, anti-tumor, and anti-fibrosis effects. However, there is still a need for systematic metabolomics analysis to further elucidate its mechanisms of action. The aim of this study was to explore the pharmacological mechanism of Corilagin.</p><p><strong>Methods: </strong>This study utilized gas chromatography-mass spectrometry (GC-MS) to analyze central target tissues, comprehensively exploring the pharmacological mechanism of Corilagin in mouse models. We identified the differential metabolites by multivariate analyses, which include principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Using MetaboAnalyst 5.0 and the KEGG database was used to depict the 12 key metabolic pathways.</p><p><strong>Results: </strong>Compared with the control group, the Corilagin induced 20, 9, 11, 7, 16, 19, 14, 15, and 16 differential metabolites in the intestine, lung, kidney, stomach, heart, liver, hippocampus, cerebral cortex, and serum, respectively. And 12 key pathways involving glucose metabolism, lipid metabolism, and amino acid metabolism were identified following Corilagin treatment.</p><p><strong>Conclusion: </strong>This research provides insight into the action mechanism of Corilagin's anti-oxidative, anti-inflammatory, anti-atherosclerotic, hepatoprotective, anti-tumor, and neuroprotective properties.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"389-404"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}