Frontiers in Pharmacology最新文献

{"title":"Impact of metabolic enzyme activity variability on dabrafenib disposition.","authors":"Shi-Yu Wang, Qing Chen, Zhong-Xi Chen, Jing Chen, Jing Yuan, Li-Shang Dai, Lian-Guo Chen, Xiao-Dan Zhang","doi":"10.3389/fphar.2025.1643618","DOIUrl":"10.3389/fphar.2025.1643618","url":null,"abstract":"<p><strong>Introduction: </strong>The systemic exposure of dabrafenib correlates with its adverse drug reactions. A thorough understanding of its pharmacokinetic profile is crucial for precise clinical application.</p><p><strong>Methods: </strong>An optimized liver microsomal incubation system was established to screen for inhibitors of dabrafenib metabolism. Recombinant human CYP3A4 microsomes were prepared using a baculovirus-insect cell expression system. Analytes were quantified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo relevance of the inhibitory effects was further validated in Sprague-Dawley rats.</p><p><strong>Results: </strong>Loratadine was identified as the most potent inhibitor, with IC₅₀ values of 14.01 ± 2.82 μM in rat liver microsomes and 52.40 ± 4.63 μM in human liver microsomes. It suppressed over 90% of dabrafenib metabolism through mixed-type inhibition. In vivo, co-administration of loratadine significantly increased the systemic exposure of dabrafenib compared to administration of dabrafenib alone. Specifically, the half-life (T_1/2) and peak concentration (C_max) increased by 548.65% and 237.43%, respectively, while CLZ/F and VZ/F were markedly reduced. These effects were attributed to inhibition mediated by loratadine. Additionally, CYP3A4 genetic polymorphisms considerably influenced the pharmacokinetics of dabrafenib: the CYP3A4.28 variant exhibited higher intrinsic clearance than the wild-type CYP3A4.1, whereas CYP3A4.8 showed reduced clearance.</p><p><strong>Discussion: </strong>Both loratadine-mediated drug-drug interactions and CYP3A4 genetic polymorphisms critically alter the metabolism of dabrafenib. Dosage adjustments are necessary when these factors are present concurrently.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1643618"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185111","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":"Buprenorphine and cannabidiol co-administration reduces survival in a mouse model of orthopedic trauma.","authors":"Caroline Bouchard, Geneviève Frégeau, Ian Massé, Louis De Beaumont","doi":"10.3389/fphar.2025.1683842","DOIUrl":"10.3389/fphar.2025.1683842","url":null,"abstract":"<p><strong>Introduction: </strong>Analgesic selection following orthopedic trauma presents unique challenges due to potential drug interactions and physiological stress. The impact of different analgesic regimens - buprenorphine, cannabidiol (CBD), their combination, or vehicle - on survival was investigated in a murine model of tibial fracture.</p><p><strong>Methods: </strong>Eighty male C57BL/6 mice were randomly assigned to one of four group: (1) Buprenorphine (0.1 mg/kg, administered subcutaneously every 12 h for 3 days) plus cannabidiol (CBD, 100 mg/kg, administered intraperitoneally once daily for 7 days); (2) CBD only; (3) Buprenorphine + vehicle; or (4) Vehicle only. All animals also received carprofen (20 mg/kg, subcutaneously, once daily for 3 days). Survival was monitored over 7 days post-injury, and necropsies were performed to identify probable causes of death.</p><p><strong>Results: </strong>Following an orthopedic trauma, mice that received buprenorphine plus CBD exhibited significantly lower survival than those that received either treatment alone or vehicle only (p = 0.0049 and p = 0.02, respectively). No differences were noted between the other groups. Necropsy revealed gastrointestinal complications in most fatalities, while two deaths were linked to acute respiratory arrest post-injection.</p><p><strong>Discussion: </strong>These findings suggest that while buprenorphine and CBD are individually well-tolerated, their co-administration may increase the risk of adverse outcomes in murine orthopedic trauma models. Combining cannabinoids and opioids in translational research requires caution and emphasizes the need for mechanistic evaluation in preclinical models.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1683842"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185356","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":"Dehydrozaluzanin C inhibits colon cancer cell proliferation, apoptosis and cycle arrest through peroxisome proliferator-activated receptor γ (PPARγ) activation.","authors":"Shan-Shan Li, Zhao-Ting Li, Xiao-Qing Zhu, Xu Li, Xi-Ke Xu, Xian-Peng Zu, Xian Li, Yun-Heng Shen","doi":"10.3389/fphar.2025.1623153","DOIUrl":"10.3389/fphar.2025.1623153","url":null,"abstract":"<p><p>Dehydrozaluzanin C (DC) is a sesquiterpene lactone isolated from Asteraceae plant <i>Ainsliaea macrocephala</i>. To investigate the antitumor effects of DC and possible molecular mechanisms for treating cancer. The antitumor effect of DC was studied using HT-29 and HCT-116 human colon tumor cell lines and Balb/c nude mice models. The anti-proliferative, proapoptotic effects, and cycle arrest of DC were observed by cell viability, colony formation, apoptosis, and cycle assays. The changes of protein expression level were examined by Western blot analysis. The transcription activity of PPARγ was determined by Luciferase reporter assay. The role of PPARγ activation in the antitumor activity of DC was verified using PPARγ antagonist GW9662 and si-PPARγ HT-29 cells. DC treatment significantly decreased colon tumor cell viability, cell clone number, and increased apoptosis rate and arrested cell cycle at S phase. Furthermore, DC treatment significantly decreased Bcl-2, CDK2, and cyclin A2 protein levels while increasing the expression of cleaved caspase 3 and Bax in HT-29 and HCT-116 cells. Further investigations indicated that cell survival, induction of apoptosis, and cycle arrest by DC could be significantly reversed following treatment with the PPARγ antagonist GW9662 or in si-PPARγ cells. <i>In vivo</i>, DC treatment significantly decreased the weight and volume of xenograft tumor tissues in mice and apoptosis-related protein levels. The results suggest that DC effectively inhibits colon tumor cell proliferation, clone formation, apoptosis, and cell cycle arrest through PPARγ activation. These results support the potential of DC as an anti-tumor lead compound for further investigation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1623153"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185379","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 on the pathogenesis, clinical impact, and traditional Chinese medicine treatment of polycystic ovary syndrome complicated by insulin resistance.","authors":"Zepu Sun, Bao Jin, Han Han, Zhen Qin, Yuqian Shi, Yuehui Zhang","doi":"10.3389/fphar.2025.1661806","DOIUrl":"10.3389/fphar.2025.1661806","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders affecting women of reproductive age. Insulin resistance (IR) is both a hallmark clinical feature and a key contributor to the pathophysiology of PCOS. Currently, metformin, along with other pharmaceuticals and lifestyle modifications, constitutes the primary approach to enhancing IR in PCOS. Despite demonstrating efficacy, some individuals exhibit suboptimal responses, and prolonged usage may lead to gastrointestinal side effects and other constraints. As an important complementary alternative medicine, recent research has highlighted traditional Chinese medicine (TCM) as a valuable adjunctive therapy for ameliorating IR in PCOS. The integration of TCM into the management of PCOS-related IR offers diverse therapeutic avenues, warranting comprehensive categorization and analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;This review systematically summarizes the pathogenesis and TCM interventions of IR in PCOS and its adverse clinical effects on patients at various stages. It primarily focuses on recent research findings, encompassing both animal studies and human studies, regarding the efficacy of TCM in ameliorating PCOS in conjunction with IR over the past 5 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This article collects relevant literature from databases such as PubMed, Web of Science, Embase, and Cochrane Library from the establishment to 2025. The search utilized the following keywords: Polycystic ovary syndrome, Insulin resistance, Polymorphism, Genetic, Epigenomics, Hyperandrogenism, Inflammation, Microbiota, Mitochondria. This review focuses on recent literature published within the last 5 years to maintain the research's contemporary relevance. Additionally, classical studies are incorporated to uphold the theoretical framework's integrity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The current evidence indicates that TCM contributes to the management of PCOS with IR primarily through modulation of gut microbiota equilibrium, suppression of inflammatory reactions (including reduction of inflammatory cytokines), amelioration of hyperandrogenism, and modulation of insulin signaling pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This review examines current research on the treatment of PCOS complicated by IR using TCM. The findings confirm the efficacy of TCM in ameliorating IR. Discrepancies in dosages and treatment durations of TCM compounds and monomers, as well as batch-to-batch variability in TCM quality, may impact treatment efficacy. Additionally, the translation of animal study outcomes to clinical settings remains unvalidated, necessitating further investigation into the synergistic effects of combined TCM and modern medicine approaches. Future efforts should focus on establishing standardized research protocols and quality control measures, enhancing the evidence base for integrated TCM and Western medicine treatments, and facilitating th","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1661806"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185329","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":"GLP-1 receptor agonists: exploration of transformation from metabolic regulation to multi-organ therapy.","authors":"Bing Gong, Couwen Li, Zhuang'e Shi, FuPing Wang, Ruanxian Dai, Guobing Chen, Heng Su","doi":"10.3389/fphar.2025.1675552","DOIUrl":"10.3389/fphar.2025.1675552","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for type 2 diabetes and obesity, have evolved into multi-organ potential therapeutics due to their pleiotropic effects beyond glycemic control. Mechanistically, GLP-1 signaling modulates immune and inflammatory pathways, regulates autophagy and pyroptosis, alleviates endoplasmic reticulum stress, and interacts with the gut microbiome. These pleiotropic effects provide a rationale for exploring their role in multiple organ systems. Clinical trials have demonstrated cardiovascular and renal protection, leading to additional approvals in high-risk populations. Early data also suggest potential benefits in liver disease, obstructive sleep apnea, chronic respiratory disorders, neurodegenerative and psychiatric conditions, reproductive dysfunction, obesity-associated cancers, and sepsis, although these remain investigational. Therefore, this review aims to synthesize the evidence on the mechanistic expansion of GLP-1RAs from metabolic regulators to systemic modulators of inflammation, autophagy, and organ protection, and explores their therapeutic repurposing across diseases.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1675552"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185340","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":"Fatty acid synthase in chemoresistance: mechanisms and therapeutic opportunities.","authors":"Li Huang, Mingjuan Zhang, Yadong Xiao","doi":"10.3389/fphar.2025.1674752","DOIUrl":"10.3389/fphar.2025.1674752","url":null,"abstract":"<p><p>Chemoresistance has been a major obstacle to the efficient treatment of cancer. Recently, targeting lipid metabolism has gained significant attention because of its roles not only in promoting cancer progression but also in inducing chemotherapy resistance. Fatty acid synthase (FAS) is the sole enzyme that is in charge of catalyzing the synthesis of palmitate, a long-chain lipid that is essential for membrane construction and post-translational modification in cell biology. Both FAS and its product, palmitate, have been validated as critical players in mediating or causing chemoresistance in cancers, although the details remain elusive, requiring further basic studies. In this mini-review, we provide a brief and concise overview of the basic research on FAS in cancer and its mechanisms of inducing chemoresistance. More importantly, we summarize and critically discuss the progress of small-molecule FAS inhibitors, especially those in clinical trials. While by far, several FAS inhibitors, including denifanstat and omeprazole, have demonstrated beneficial effects in clinical trials, no candidate has been approved by the FDA. We concluded here that targeting FAS is a feasible strategy to overcome chemoresistance, although more interdisciplinary efforts are needed to identify a potent, specific, and bioavailable FAS inhibitor for clinical applications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1674752"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185354","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":"The role of curcumin in modulating nutritional status and susceptibility to <i>Mycoplasma</i> pneumoniae infection in children.","authors":"Chun-Jing Liu, Wei Liu, Hong-Xiu Yang, Li-Hua Li","doi":"10.3389/fphar.2025.1651875","DOIUrl":"10.3389/fphar.2025.1651875","url":null,"abstract":"<p><strong>Background: </strong><i>Mycoplasma pneumoniae</i> remains a leading cause of pediatric respiratory infections, often resulting in prolonged symptoms, hospitalization, and systemic inflammation. Curcumin has been proposed as an adjunctive therapy due to its anti-inflammatory and immunomodulatory properties. This study retrospectively evaluated the association between adjunctive curcumin supplementation and clinical, immunological, and nutritional outcomes in children with confirmed <i>M. pneumoniae</i> infection.</p><p><strong>Methods: </strong>We performed a retrospective observational study of children aged 1-12 years at Beijing Luhe Hospital (September 2023-May 2024). Based on charted treatment, 160 patients were categorized into a curcumin-supplemented group (n = 80; standardized 95% curcuminoids, 20 mg/kg/day, with antibiotics) or a control group (n = 80; antibiotics alone). Outcomes included duration of fever/cough, hospitalization, severe complications, inflammatory markers-C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)-pathogen-specific antibodies, and nutritional indices (body mass index [BMI], hemoglobin, serum albumin). Adverse events (AEs) were summarized.</p><p><strong>Results: </strong>Baseline characteristics were comparable between groups (all p > 0.05). The curcumin group had shorter fever (3.2 ± 1.1 vs. 4.5 ± 1.3 days, p = 0.01) and cough durations (5.4 ± 2.0 vs. 7.1 ± 2.5 days, p = 0.02), lower hospitalization rates (1.25% vs. 10.0%, p = 0.02), and fewer severe complications (2.5% vs. 12.5%, p = 0.03). Greater reductions were observed in CRP (-9.6 ± 5.1 vs. -1.8 ± 4.7 mg/L, p = 0.011), IL-6 (-15.1 ± 6.3 vs. -2.5 ± 5.8 pg/mL, p = 0.01), and TNF-α (-9.6 ± 5.4 vs. -1.7 ± 5.1 pg/mL, p = 0.03), with a larger increase in <i>M. pneumoniae</i>-specific antibodies (+30 ± 15 vs. +5 ± 12 AU/mL, p = 0.001). Antibiotic use (6.5 ± 1.8 vs. 7.8 ± 2.0 days, p = 0.014) and total recovery time (8.2 ± 2.1 vs. 10.5 ± 2.5 days, p = 0.001) were shorter in the curcumin group. Nutritional indices showed improvement in hemoglobin (p = 0.01) and serum albumin (p = 0.02), while BMI showed a non-significant increase (p = 0.368). AE incidence was low and similar (6.3% vs. 8.8%, p = 0.55). In multivariable regression, curcumin remained independently associated with shorter recovery (β = -1.2, p = 0.001).</p><p><strong>Conclusion: </strong>Curcumin might be a safe and well-tolerated adjunct to standard antibiotic therapy in children with <i>M. pneumoniae</i> infections, potentially improving clinical outcomes, reducing inflammation, and supporting nutritional status.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1651875"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185387","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":"Antibacterial and wound healing effects of PEG-coated ciprofloxacin-loaded ZIF-8 nanozymes against ciprofloxacin-resistant <i>Pseudomonas aeruginosa</i> taken from burn wounds.","authors":"Mohadeseh Pahlevani, Masoumeh Beig, Seyed Mahmoud Barzi, Milad Sadeghzadeh, Morvarid Shafiei, Mohsen Chiani, Aria Sohrabi, Mohammad Sholeh, Shaghayegh Nasr","doi":"10.3389/fphar.2025.1556335","DOIUrl":"10.3389/fphar.2025.1556335","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial-resistant (AMR) <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) poses a significant challenge in burn wound infections due to its biofilm formation and resistance mechanisms, particularly against ciprofloxacin (CIP). Innovative therapies are urgently needed to improve treatment outcomes for burn patients. This study aimed to develop and evaluate Polyethylene glycol (PEG)-Coated CIP-Loaded zeolitic imidazolate framework-8 (ZIF-8) nanozymes (PEG-ZIF-8-CIP) to enhance antimicrobial efficacy against CIP-resistant <i>P. aeruginosa</i> (CRP) and promote wound healing.</p><p><strong>Methods: </strong>Clinical isolates of CRP were collected from burn patients and confirmed via polymerase chain reaction for the <i>oprL</i> gene. ZIF-8 nanozymes were synthesized, loaded with CIP, and coated with polyethylene glycol to form PEG-ZIF-8-CIP. These nanozymes were characterized using field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, and zeta potential measurements. Their antimicrobial efficacy, biofilm eradication capability, CIP release, and superoxide dismutase-like activity were assessed; Cytotoxicity Assay and wound healing effects were evaluated in a murine burn model infected with CRP. Statistical analyses were performed using ANOVA with Tukey correction in GraphPad Prism (v10.2.1), considering p-values < 0.05 as statistically significant.</p><p><strong>Results: </strong>Among 60 <i>P. aeruginosa</i> isolates, 40 were confirmed as ciprofloxacin-resistant (CRP) and carried the <i>oprL</i> gene. PEG-ZIF-8-CIP nanozymes achieved high drug entrapment efficiency (75%) and strong stability (zeta potential: -31.7 mV), with uniform spherical morphology (∼600 nm). Drug release followed a biphasic pattern-50% released in 6 h, ∼90% by 72 h. The nanozymes showed potent antimicrobial and antioxidant activity, with low MBECs and rapid absorbance reduction. Cytotoxicity was lowest for PEG-ZIF-8-CIP, especially at 24-48 h. <i>In vivo</i>, PEG-ZIF-8-CIP accelerated burn wound healing, reduced inflammation, promoted fibroblast growth and collagen deposition, and achieved the highest bacterial clearance (up to 84%).</p><p><strong>Conclusion: </strong>PEG-ZIF-8-CIP nanozymes effectively treated ciprofloxacin-resistant <i>P. aeruginosa</i> in burn-wound models by combining strong antimicrobial and anti-biofilm activity with improved wound healing. Encapsulation in ZIF-8 boosted antibiotic potency, while PEGylation enhanced stability, reduced toxicity, and enabled sustained drug release-highlighting their strong potential for combating antimicrobial-resistant wound infections.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1556335"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185416","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":"Mechanisms and advantages of natural derived small molecule compounds in the prevention and treatment of colorectal cancer: a review.","authors":"Ming-Jie Liao, Hao-Yu Dong, Gang Chen, Wei-Wei Li, Guo-Feng Li","doi":"10.3389/fphar.2025.1658493","DOIUrl":"10.3389/fphar.2025.1658493","url":null,"abstract":"<p><p>Globally, colorectal cancer (CRC) ranked third in cancer prevalence and emerged as the primary contributor to cancer-related fatalities in 2022, with projections indicating substantial escalation by 2040. The malignant progression of healthy colonic cells involves complex interactions among multiple cellular pathways over extended periods (typically exceeding 10 years), influenced by dietary patterns, lifestyle factors, and genetic predispositions. In addition, marked disparities in CRC incidence and mortality appear to show large differences across geographic regions, demographic groups, and biological sexes, suggesting that there are traces of CRC. Therefore, timely intervention or regression of the development of CRC, particularly targeting high-risk populations, may be an excellent strategy to reduce CRC burden in forthcoming decades. Natural derived small molecule compounds (NDSMCs) exhibit significant advantages, including structural diversity, unique biological activities, low toxicity and multi-target effects. Increasing evidence suggests that NDSMCs demonstrate therapeutic potential against CRC through multi-target mechanisms, such as modulation of gut microbiota, induction of ferroptosis, and regulation of programmed cell death pathways (apoptosis/autophagy), thereby offering promising avenues for CRC treatment. However, comprehensive reviews in this field remain scarce. Consequently, this study systematically summarizes the research advancements over the past 5 years regarding the mechanisms of NDSMCs in combating CRC, aiming to provide valuable insights for therapeutic strategies, preventive measures, and novel drug development. Furthermore, the clinical progress and limitations of certain NDSMCs in CRC treatment are also discussed.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1658493"},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148531","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":"Advancements in nasal drug delivery system of natural products.","authors":"Yenna Hsu, Jiajing Yang, Miaoyang Cao, Ting Xu, Jia He, Huarong Hong, Luyun Jiang, Shunlin Peng, Peizheng Xiong","doi":"10.3389/fphar.2025.1667517","DOIUrl":"10.3389/fphar.2025.1667517","url":null,"abstract":"<p><strong>Background: </strong>Nasal drug delivery offers a non-invasive route with rapid absorption and the ability to bypass first-pass metabolism, making it promising for central nervous system (CNS) disorders, nasal diseases such as allergic rhinitis, and other chronic conditions by enabling targeted delivery and crossing the blood-brain barrier.</p><p><strong>Purpose: </strong>To review the advantages of nasal delivery, therapeutic potential of natural products, and how drug delivery systems may overcome bioavailability and solubility issues.</p><p><strong>Study design: </strong>A literature review analyzing mechanisms, clinical applications, and limitations of natural products in nasal delivery.</p><p><strong>Methods: </strong>Relevant articles published before January 2025 were retrieved from Google Scholar, PubMed, ScienceDirect, Scopus, Web of Science, Springer, and official sources.</p><p><strong>Results: </strong>Nasal administration improves the bioavailability and absorption of natural products, enhancing anti-inflammatory, antioxidant, neuroprotective, and anti-allergic effects. However, poor solubility and stability remain barriers, which may be mitigated by nanocarriers, liposomes, and other advanced systems.</p><p><strong>Conclusion: </strong>Combining nasal drug delivery with natural products is a promising strategy for treating CNS, nasal, and chronic diseases, potentially improving clinical efficacy and expanding therapeutic options.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1667517"},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148410","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}