Drug Design, Development and Therapy最新文献

{"title":"Cardioprotection Through Pharmacological Activation of Sirtuin 5 in a Murine Model of Acute Myocardial Infarction.","authors":"Carola Castiello, Panagiotis Efentakis, Panagiota-Efstathia Nikolaou, Lydia Symeonidi, Christina Chania, Ioanna Barla, Ifigeneia Akrani, Nikolaos Kostomitsopoulos, Evangelos Gikas, Nikolaos S Thomaidis, Emmanuel Mikros, Petra Kleinbongard, Rossella Fioravanti, Clemens Zwergel, Sergio Valente, Antonello Mai, Ioanna Andreadou","doi":"10.2147/DDDT.S509337","DOIUrl":"10.2147/DDDT.S509337","url":null,"abstract":"<p><strong>Purpose: </strong>Sirtuins (SIRTs) play a critical role in redox and metabolic regulation of the myocardium; however, the cardioprotective potential of SIRT5 in terms of infarct size (IS) reduction is still elusive. Herein, we employed the newly synthesized SIRT5-specific agonist, MC3215, developed by our group, to explore for the first time the pharmacological activation of SIRT5 as a target for cardioprotection.</p><p><strong>Methods and results: </strong>In in vitro screening experiments, SIRT1 and SIRT5 agonists, namely, MC2606 and MC3215, at 1-20 μΜ were added to cardiomyoblasts (H9c2) and human endothelial cells (EA.hy-926) during 24 h hypoxia/2 h reoxygenation (H/R). SIRT1 and SIRT5 agonists mitigated H/R injury. Male C57BL/6J mice underwent 30 min ischemia (I) followed by 2 h or 24 h reperfusion (R). Mice received vehicle, the SIRT1 or SIRT5 agonists at 20 and 30 mg/kg at the 20th min of ischemia, and IS was quantified via triphenyl-tetrazolium chloride staining (n=5-7/group). MC3215-mediated SIRT5 activation reduced IS at 24 h R at 20mg/kg compared to controls (25.18±2.7% vs 38.80±4.7%). MC3215 treatment resulted in reduced protein malonylation in all experimental settings. Targeted mass-spectrometry-based metabolomics in the ischemic heart at the 10^th min of R suggested increased fatty acid oxidation, as indicated by increased N³-Trimethyllysine and D-pantothenate. Concomitantly, molecular analysis indicated that the SIRT5 agonist activated AMPKα and Reperfusion Injury Salvage Kinase (RISK) pathway. Additionally, at 3 h reperfusion, MC3215 led to increased mitofusin 2 without altering apoptosis, paving towards improved mitochondrial dynamics. Co-administration of SIRT5 inhibitor, TW-37, abrogated MC3215-mediated cardioprotection.</p><p><strong>Conclusion: </strong>SIRT5 pharmacological agonism emerges as a novel cardioprotective target, leading to RISK pathway activation and mitochondria-related metabolic effects, converging at salvaging ischemic myocardium from I/R injury.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5489-5505"},"PeriodicalIF":4.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552502","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":"Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance.","authors":"Jing-Yi Chen, Ying-Tzu Chang, Yu-Cheng Ho, Yu-Ning Teng","doi":"10.2147/DDDT.S521116","DOIUrl":"10.2147/DDDT.S521116","url":null,"abstract":"<p><strong>Purpose and study design: </strong>Multi-drug resistance (MDR) in cancer significantly hinders effective treatment, leading to poor patient outcomes. The study investigates the potential of natural compounds, Alisol B 23-acetate (B23) and Alisol A 24-acetate (A24), to reverse MDR through various mechanisms on cancer cell membranes.</p><p><strong>Results: </strong>Cytotoxicity assays established non-toxic concentrations of B23 and A24, which were then tested in drug-sensitive and drug-resistant cancer cell lines with or without chemotherapeutic drugs. Both compounds significantly enhanced reactive oxygen species (ROS) production and apoptosis in HepG2/VIN MDR cells while preserving cell membrane integrity. They also improved membrane fluidity and inhibited the function of P-glycoprotein (P-gp) efflux transporters in both HepG2/VIN and <i>ABCB1</i>/Flp-In^TM-293, leading to increased drug accumulation. Molecular docking studies revealed that B23 and A24 interact with distinct binding sites on P-gp, demonstrating allosteric and competitive inhibition.</p><p><strong>Conclusion: </strong>B23 and A24 effectively reverse cancer MDR by (1) modulating ROS levels and inducing apoptosis, (2) maintaining membrane integrity but improving membrane fluidity, and (3) inhibiting drug efflux by membrane transporters. These findings provide a promising basis for developing new therapeutic strategies to combat MDR in cancer, highlighting the potential use of these natural product derivatives in adjunctive cancer therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5471-5488"},"PeriodicalIF":4.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526868","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":"Overview and Prospects of the Clinical Application of Oliceridine.","authors":"Kun Yi, Wenjie Sun, Wen Yu, Shibiao Chen","doi":"10.2147/DDDT.S525471","DOIUrl":"10.2147/DDDT.S525471","url":null,"abstract":"<p><p>Opioids can effectively relieve pain but carry risks of addiction and adverse effects. Oliceridine, a G protein-biased μ-Opioid receptor (MOR) agonist, has emerged as a promising safer alternative. By preferentially activating G-protein-biased agonist targeting the μ-opioid receptor while downregulating β-arrestin2 recruitment, oliceridine (Olinvyk) achieves potent analgesia with reduced incidence of opioid-related adverse effects. Supported by robust preclinical data, oliceridine has demonstrated significant clinical potential, prompting global clinical trials to define its optimal indications and therapeutic scenarios. This review synthesizes current evidence on oliceridine's efficacy, safety, and mechanistic specificity across diverse surgical settings, contrasting its profile with conventional opioids. Additionally, we discuss future research priorities, including dose optimization, expansion into chronic pain management, and long-term safety evaluation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5415-5430"},"PeriodicalIF":4.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539529","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 Use of Fospropofol Disodium: Evaluation of Pharmacology, Safety, and Efficacy.","authors":"Congcong Zou, Hongyang Chen, Yanhua Qiu","doi":"10.2147/DDDT.S516789","DOIUrl":"10.2147/DDDT.S516789","url":null,"abstract":"<p><p>Fospropofol disodium (FD) is a safe and effective alternative to propofol, as it avoids injection pain, severe hypotension, significant respiratory depression, and allergic reactions during intravenous anesthesia induction. FD, the water-soluble prodrug of propofol, was initially developed by Eisai in Japan and was approved by the FDA for marketing in the United States in 2008. However, due to formaldehyde accumulation, safety concerns in outpatient settings, and the requirement for administration by anesthesiologists, the product had poor sales and was withdrawn in 2012. Subsequently, short-term FD use was found resulting in limited formaldehyde accumulation, which is then metabolized to formate at levels comparable to endogenous concentrations, posing no significant health risk. Most adverse events, including respiratory depression and hypotension, were found to be transient, self-limiting, and predominantly mild to moderate in severity. On May 25, 2021, the National Medical Products Administration (NMPA) approved the injection of FD, with the approval number H20210017. As a new type Class I drug applied for market registration in China, it is indicated for general anesthesia induction in adults. The review covers the known and emerging characteristics of pharmacokinetic and pharmacodynamic properties of FD approved by the FDA and the new type Class I FD approved by China, emphasizing their non-inferior sedative efficacy and relatively mild adverse reactions compared to propofol and provides insights into their safer application in a broader population. Additionally, it highlights the necessity of structured personnel management during sedation and anesthesia procedures. In short, FD can be safely and effectively used for endoscopic examinations, minor surgeries and continuous sedation in the ICU. While FD demonstrates safety and efficacy as a sedative in specific clinical scenarios, larger and more rigorous clinical trials are essential to validate its long-term use, application in high-risk populations, and administration by non-anesthesiologist healthcare providers.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5453-5460"},"PeriodicalIF":4.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526870","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":"A Comparison of in-vitro Pharmacokinetics and Pharmacodynamics of Branded and Its Locally Produced Cefuroxime Sodium Against <i>Staphylococcus</i> and <i>Escherichia Escherichia coli</i>.","authors":"Mengjiao Du, Tingting Sun, Xueting Wang, Xiaohui Chi, Yonghong Xiao","doi":"10.2147/DDDT.S511271","DOIUrl":"10.2147/DDDT.S511271","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the in-vitro antibacterial effects of branded and its locally produced cefuroxime sodium against <i>Staphylococcus</i> ATCC29213, clinical strains of methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA) 164342 and methicillin-sensitive coagulase-negative <i>staphylococci</i> (MSCNS) 117933, and <i>Escherichia coli</i> ATCC25922, and to provide a reference for their clinical use.</p><p><strong>Methods: </strong>An in-vitro antibacterial susceptibility test, time-kill curve and pharmacokinetics and pharmacodynamics (PK/PD) modeling was used in the comparison.</p><p><strong>Results: </strong>The minimum inhibitory concentrations (MIC) of the two types of cefuroxime sodium were identical against four bacterial strains; both types of cefuroxime sodium had MICs of 0.5 μg/mL, 8 μg/mL, 0.5 μg/mL, and 0.25 μg/mL against ATCC 29213, ATCC 25922, M164342 and MSCNS117933, respectively. There were no significant differences in the time-kill curves of the two forms against the four strains at three concentrations. At drug concentrations of 2×MIC and 4×MIC, the bacterial count of all the strains decreased from 6 log CFU/mL to around 4 log CFU/mL. The bactericidal efficacies of the two agents were generally similar in the pharmacokinetics model of simulated intravenous drug administration of 1 g q8h. Only the PD parameter of bactericidal rate (KR) for ATCC 29213 and the area difference between the drug bactericidal curve and the bacterial growth control curve (I_E) for ATCC25922 were statistically different. The KR and I_E of the locally produced form were 0.73±0.10 logCFU·h/mL and 83.73±12.69 logCFU·h/mL, respectively, while the KR and I_E of the branded form were 1.19±0.07 logCFU·h/mL and 104.02±16.28 logCFU·h/mL, respectively.</p><p><strong>Conclusion: </strong>The in-vitro antibacterial effect of locally produced cefuroxime sodium against <i>Staphylococci</i> and <i>E. coli</i> is comparable to that of branded cefuroxime sodium.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5461-5470"},"PeriodicalIF":4.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526867","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":"Therapeutic Potential of Curcumin and Novel Formulations in Psoriasis Treatment: Evidence and Future Prospects.","authors":"Tattiya Kantasa, Kankanit Yeerong, Preeyaporn Klinjan, Mingkwan Na Takuathung, Kornvipa Settakorn, Mati Chuamanochan, Napatra Tovanabutra, Chadarat Ampasavate, Nut Koonrungsesomboon","doi":"10.2147/DDDT.S520555","DOIUrl":"10.2147/DDDT.S520555","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory skin disease characterized by thickened, erythematous, and scaly plaques that significantly impact patients' quality of life. Although various treatments are available, they often cause adverse effects, prompting the exploration of alternative therapies. Curcumin, a bioactive compound in <i>Curcuma longa</i> Linn. (turmeric), has demonstrated potential benefits in managing psoriasis. This article aims to comprehensively evaluate the anti-psoriatic activity, efficacy, and safety profiles of curcumin and its novel formulations, as well as to discuss future directions for enhancing their use as an alternative treatment for psoriasis. Curcumin exerts its anti-psoriatic effects through multi-targeted actions, including inhibiting cell proliferation, inducing apoptosis, suppressing pro-inflammatory cytokines, and enhancing skin barrier proteins, thereby alleviating psoriasis lesions. However, both oral and topical curcumin formulations face challenges, such as low bioavailability and limited skin penetration, underscoring the need for novel formulations to improve therapeutic outcomes. Clinical findings suggest that oral curcumin may provide greater efficacy and better tolerance as an adjunctive therapy for moderate to severe psoriasis, while topical formulations may help reduce severity and improve well-being in mild to moderate cases. Overall, curcumin and its novel formulations show promise as therapeutic agents for psoriasis treatment. However, further research, particularly large-scale clinical trials, is essential to evaluate long-term efficacy and safety comprehensively.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5387-5414"},"PeriodicalIF":4.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526873","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":"Ciprofol Versus Propofol for Sedation in Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis in a Chinese Population.","authors":"Hongyu Yang, Ping Lai, Xiaoyu Qin, Yiyang Cui, Xiaojia Zhang, Haiqing Zhang, Yichen Ding, Ersheng Ye, Yaping Wu, Bingxu Ren","doi":"10.2147/DDDT.S522678","DOIUrl":"10.2147/DDDT.S522678","url":null,"abstract":"<p><strong>Purpose: </strong>Ciprofol (HSK3486) is a novel intravenous anesthetic structurally similar to propofol; however, its advantages over propofol remain unclear. This study aimed to compare the safety, efficacy, and satisfaction outcomes of ciprofol and propofol during gastrointestinal endoscopy.</p><p><strong>Patients and methods: </strong>This systematic review incorporated all available comparative trials assessing ciprofol versus propofol for endoscopic sedation following a comprehensive search strategy across eight biomedical databases-Web of Science, Embase, PubMed, and Cochrane Library, along with major Chinese repositories (CNKI, Wanfang, CBM, and VIP)-through September 2023. Evidence synthesis was conducted per PRISMA guidelines, with methodological rigor enhanced through prospective trial registry screening and implementation of GRADE framework for evidence grading.</p><p><strong>Results: </strong>This systematic review included 45 randomized controlled trials involving 6884 patients who met predefined methodological and clinical eligibility thresholds. Very low to moderate certainty evidence showed that ciprofol induced sedation or anesthesia comparable to that of propofol (relative risk [RR]: 1.00, 95% confidence interval [CI]: 1.00 to 1.01), with both agents demonstrating similar procedural efficiency. Furthermore, ciprofol was associated with a reduced incidence of complications, including hypotension (RR: 0.60, 95% CI: 0.51 to 0.70), bradycardia (RR: 0.69, 95% CI: 0.56 to 0.85), nausea and vomiting (RR: 0.67, 95% CI: 0.54 to 0.84), hypoxia (RR: 0.38, 95% CI: 0.31 to 0.48), respiratory depression (RR: 0.39, 95% CI: 0.28 to 0.56), apnea (RR: 0.35, 95% CI: 0.23 to 0.53), and injection pain (RR: 0.13, 95% CI: 0.09 to 0.17), while also enhancing patient and anesthesiologist satisfaction.</p><p><strong>Conclusion: </strong>Ciprofol-induced sedation or anesthesia was comparable to propofol, with both drugs demonstrating similar procedural efficiency. However, ciprofol was associated with lower risk of adverse reactions and higher satisfaction among patients and anesthesiologists. Ciprofol may represent a superior sedative option for gastrointestinal endoscopy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5369-5385"},"PeriodicalIF":4.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526869","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":"Uncovering the Efficacy and Mechanism of Zhenwu Decoction for Hypothyroidism Based on Non-Targeted Metabolomics.","authors":"Yuhan Wang, Yancun Li, Mengyao Tang, Luhan Zhang, Shu Zhu","doi":"10.2147/DDDT.S527163","DOIUrl":"10.2147/DDDT.S527163","url":null,"abstract":"<p><strong>Background: </strong>Hypothyroidism, a systemic hypometabolic syndrome from deficient thyroid hormone synthesis/utilization, has high prevalence and complex mechanisms. Levothyroxine-based lifelong therapy risks neurocognitive/metabolic complications and iatrogenic pathologies (eg, osteoporosis, hepatocardiac dysfunction). Zhenwu Decoction (ZW), a classical multi-target herbal formulation, shows therapeutic potential but requires mechanistic clarity on thyroid restoration to enable standardized translation.</p><p><strong>Objective: </strong>To investigate ZW's therapeutic mechanisms in hypothyroidism via serum metabolomics and pathway analysis.</p><p><strong>Methods: </strong>Twenty-seven Wistar rats were randomly divided into three groups: control group (n=9), PTU model group (n=9), and Zhenwu Tang group (n=9). The hypothyroidism rat model was induced by administering propylthiouracil (PTU) by gastric gavage for 4 weeks in the PTU model and Zhenwu Tang groups, while the control group received no treatment. Subsequently, the Zhenwu Tang group underwent a 3-week herbal medicine intervention. Multidimensional validation (including phenotypic monitoring, ELISA for FT4/TSH, and HE staining) was performed to confirm the successful establishment of the model and to evaluate the therapeutic efficacy of Zhenwu Tang (ZW). Untargeted UPLC-MS/MS metabolomics was performed to identify differential metabolites (VIP >1, p <0.05), and MetaboAnalyst 5.0 was used to map key pathways.</p><p><strong>Results: </strong>ZW can significantly improve systemic indicators (body weight, anal temperature, feeding behavior) in hypothyroid rats. It remarkably improves the histopathological features of the thyroid gland, approaching the structure of the normal group. In addition, ZW can significantly regulate serum thyroid hormone levels (decrease TSH and increase FT4), approaching normal levels.47 metabolites (eg, L-proline, fumaric acid, estradiol) and 7 pathways (thermogenesis, cholesterol metabolism) were identified. ZW corrected metabolic dysfunction through multi-target regulation.</p><p><strong>Conclusion: </strong>ZW exerts therapeutic effects by modulating glucose-6-phosphate, bile acids, and critical metabolic pathways, thereby advancing our understanding of hypothyroidism pathophysiology and underscoring its potential for clinical translation and therapeutic development.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5431-5451"},"PeriodicalIF":4.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526885","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 Treatment of Functional Dyspepsia Using Traditional Chinese Medicine: A Review Based on Pathophysiological Perspectives.","authors":"Mingming Fan, Xiangbin Pan, Yingzhe Liu","doi":"10.2147/DDDT.S514042","DOIUrl":"10.2147/DDDT.S514042","url":null,"abstract":"<p><p>Functional dyspepsia (FD) is a common functional gastrointestinal disorder characterized by epigastric pain and symptoms related to meal consumption. According to recent diagnostic criteria, FD can be classified as epigastric pain syndrome (EPS) or postprandial discomfort syndrome (PDS), based on the predominant symptoms. The pathophysiology of FD can be influenced by various factors, including microinflammation, gastrointestinal infections, abnormal gastroduodenal motility, visceral hypersensitivity, disturbances in the brain-gut axis, and psychological factors. As a result, its management requires a comprehensive approach that includes both pharmacological and non-pharmacological interventions such as psychological therapies and adjunctive treatments. However, despite the availability of various treatment options, no contemporary pharmacological agents have been approved specifically for FD. In this context, Traditional Chinese Medicine (TCM) has emerged as a promising alternative that offers notable efficacy and safety in managing FD. Various TCM modalities, including herbal prescriptions, acupuncture, moxibustion, and music therapy have demonstrated therapeutic potential. In this article, we discuss the pathophysiology of FD from a modern medical perspective and describe integrative treatment strategies based on TCM, highlighting the potential benefits of combining the traditional and contemporary approaches.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5349-5367"},"PeriodicalIF":4.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526871","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":"Therapeutic Effect of <i>Brucea Javanica</i> Oil Emulsion in Mice with Irinotecan-Induced Delayed Diarrhea.","authors":"Zixuan Lai, Yong Zhang, Xiaoxia Hu, Li Chen, Weimu Huang, Juan Wang, Baoyi Chen, Mihong Ren, Bowen Yang, Ziren Su, Jiannan Chen, Jianhui Xie, Zhengquan Lai, Youliang Xie","doi":"10.2147/DDDT.S517973","DOIUrl":"10.2147/DDDT.S517973","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced diarrhea (CID), particularly delayed diarrhea, often limits clinical use. <i>Brucea javanica</i> oil emulsion (BJOE), an adjuvant chemotherapy agent, has been shown to reduce irinotecan-related gastrointestinal side effects. However, its underlying molecular mechanism remains unclear. The cGAS-STING pathway, composed of the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the adaptor protein stimulator of interferon genes (STING), plays an essential role in delayed diarrhea. This work aimed to investigate the therapeutic potential and underlying mechanism of BJOE on irinotecan-induced delayed diarrhea.</p><p><strong>Methods: </strong>Gas chromatography-mass spectrometry (GC-MS) was employed to explore the components of BJOE. Macro-observation, histology, PCR, immunohistochemistry, and Western blotting were performed to illuminate the potential mechanism of BJOE on irinotecan-induced delayed diarrhea mice model.</p><p><strong>Results: </strong>GC-MS analysis identified linoleic acid (20.67%) as BJOE's main component. BJOE effectively mitigated irinotecan-induced delayed diarrhea in mice, as characterized by attenuation of weight loss, colon shortening, hematochezia, and histopathologic damage. It significantly inhibited the mRNA expression levels of inflammatory mediators TNF-α, IL-1β, IL-6, and iNOS, and upregulated barrier gene expression (ZO-1 and occludin). Furthermore, BJOE markedly enhanced mucin production, and increased PCNA protein expression. Concurrently, BJOE remarkably down-regulated the colonic mRNA levels of cGAS, STING, CXCL10, CCL5, and IFN-β. Activation of the cGAS-STING pathway with agonist DMXAA significantly reduced BJOE's therapeutic, anti-inflammatory, and barrier-protective effects. Similarly, stimulating STING substantially reversed BJOE's inhibition on cGAS-STING pathway.</p><p><strong>Conclusion: </strong>BJOE effectively mitigated inflammation and preserved intestinal barrier function, at least partially, via inhibiting cGAS-STING pathway in irinotecan-induced delayed diarrhea. Active components, long-term safety and pharmacokinetics studies were warranted to facilitate translational application.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5329-5347"},"PeriodicalIF":4.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526872","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}