Phytotherapy Research最新文献

{"title":"Efficacy and Safety of Rosa canina L. and a Traditional Polyherbal Formulation Syrup in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Factorial Randomized Double-Blind Placebo-Controlled Clinical Trial.","authors":"Haide Golsorkhi, Hadi Montazerlotfelahi, Elham Abniki, Mohammad Vafaee-Shahi, Mohammad Kamalinejad, Mostafa Qorbani, Mohsen Bahrami, Majid Dadmehr","doi":"10.1002/ptr.70061","DOIUrl":"10.1002/ptr.70061","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder in children and adolescents. A number of patients do not respond adequately to psychostimulant medications or sometimes experience intolerable side effects. The present study was conducted to determine the efficacy and safety of Rosa canina L. and a traditional polyherbal formulation (PHF) syrup on ADHD as a complementary treatment. Ninety ADHD patients aged 5-14 years based on DSM-5 diagnostic criteria were randomly divided into three groups to receive (1) R. canina syrup + methylphenidate (MPH), (2) PHF syrup + MPH, and (3) placebo syrup + MPH for 8 weeks. The Conners' Teacher Rating Scale (CTRS) and Conners' Parent Rating Scale (CPRS) as well as the Child Symptom Inventory-4 (CSI-4) questionnaires were completed before the intervention and then every 4 weeks for 2 months. The results showed that the decreasing trend of intra-group changes in the sum of CTRS, CPRS, and CSI-4 was statistically significant in three groups (p < 0.0001, p < 0.0001, p < 0.001, respectively). The study of intergroup changes in the CTRS (p = 0.02) and CSI-4 (p = 0.04) was significant and the CPRS was not significant (p = 0.15). Also, a significant increase in the total quality of life scores was reported in the three groups (p < 0.0001), but no significant difference was observed between them (p = 0.27). Therefore, R. canina and PHF syrups in combination with standard medical treatment could provide more clinical benefits for ADHD patients.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4116-4125"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products in the 21^st Century: Revolutionizing Therapeutics With Flavonoids as Key Phytometabolites.","authors":"P Krishna, Aatif Subhan, Khushi Gupta, Avadh Biharee, Suresh Thareja","doi":"10.1002/ptr.70035","DOIUrl":"10.1002/ptr.70035","url":null,"abstract":"<p><p>Flavonoids, distinguished by their structural diversity and broad-spectrum activities, represent a promising class of phytochemicals with substantial therapeutic potential. Ubiquitous in plants, these polyphenolic compounds play crucial roles in pigmentation defense and are well recognized for their protective effects against cancer, metabolic, and neurodegenerative disorders. The ability of flavonoids to interact with diverse molecular targets and regulate critical signaling pathways underscores their relevance in preclinical and clinical settings. The present review critically consolidates recent advances in the therapeutic profile of flavonoids, covering their biosynthetic pathways, molecular structures, and extraction methodologies. Emphasis is given on their pharmacological effects in cancer, metabolic, microbial, respiratory, and nutraceutical applications. The mechanistic basis of their multi-targeted actions is also discussed and supported by emerging clinical data. By outlining the current advancements, key challenges, and future perspectives, this review advocates for incorporating flavonoid-based interventions into clinical practice and highlights their potential as effective alternatives to conventional therapies.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3833-3867"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Baicalein as a Novel Ubiquitin-Specific Protease 21 Inhibitor for the Treatment of Hepatocellular Carcinoma.","authors":"Huijun Jia, Zhuoyue Zhao, Chen Su, Jiapeng Du, Shuaizhou Yang, Jiankun Song, Xu Han, Fang Yu, Zhaolin Sun, Peng Chu","doi":"10.1002/ptr.70022","DOIUrl":"10.1002/ptr.70022","url":null,"abstract":"<p><p>Ubiquitin-specific protease 21 (USP21) is amplified and overexpressed in hepatocellular carcinoma (HCC), correlating with poor prognosis, suggesting USP21 inhibition as a therapeutic strategy. This study aims to identify novel USP21 inhibitors and elucidate their molecular mechanisms in HCC treatment. USP21 inhibitors were identified via structure-guided drug discovery, enzymatic assays, and bio-layer interferometry. Functional validation included proliferation, migration, colony formation, and apoptosis assays. USP21-mediated hypoxia-inducible factor-1α (HIF-1α) regulation was assessed using qRT-PCR, co-immunoprecipitation, and deubiquitination assays. In vivo efficacy was evaluated in murine allograft models, with binding modes resolved via molecular dynamics simulations and binding free energy calculations. Screening 4000 natural compounds identified Baicalein and Hypericin as USP21 inhibitors (50% inhibitory concentration: 2.45 and 17.68 μM, respectively). Baicalein suppressed HCC proliferation, colony formation, and migration while inducing apoptosis. Mechanistically, USP21 directly stabilized HIF-1α via deubiquitination, which Baicalein disrupted by blocking the USP21-HIF-1α interaction, promoting HIF-1α degradation. In vivo, Baicalein inhibited tumor growth and enhanced intratumoral T-cell infiltration. Structural analyses identified Gln300, His510, and Gly517 as critical residues for USP21-inhibitor binding. Baicalein emerges as a dual-functional USP21 inhibitor that destabilizes HIF-1α and reprograms the tumor immune microenvironment. The Gln300/His510/Gly517 binding motif provides a structural blueprint for advanced USP21-targeted drug design, establishing USP21 inhibition as a promising therapeutic strategy for HCC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3935-3951"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effects of Vaccinium myrtillus Supplementation on Cardiometabolic Indices: A Systematic Review and Meta-Analysis.","authors":"Shokoofeh Talebi, Mahsa Shirani, Atena Mahdavi, Mohammad Bagherniya, Amirhossein Sahebkar","doi":"10.1002/ptr.70054","DOIUrl":"10.1002/ptr.70054","url":null,"abstract":"<p><p>Chronic diseases cause early death and financial strain worldwide. Cardio-metabolic health, crucial for preventing cardiovascular disease and type 2 diabetes, may benefit from bilberry's antioxidant and anti-inflammatory properties. This meta-analysis reviews studies of bilberry's impact on lipid profiles, glycemic indices, body composition, and inflammatory and oxidative factors. Inclusion criteria were randomized clinical trials assessing bilberry supplementation in adults for at least 1 week. A comprehensive review of literature was performed in PubMed, Web of Science, Scopus, and Google Scholar until July 21, 2024, without any time limitations. Mean changes and their SDs were used to calculate overall effect sizes, with the Hozo et al. method converting SEs, 95% CIs, and IQRs to SDs. A random-effects model accounted for between-study variations. Eleven RCTs, including 409 individuals, were incorporated into the present systematic review, and 8 were included in the meta-analysis. Combining five effect sizes from the five trials on long-term effects of bilberry administration compared with controls resulted in a non-significant decrease in FBG (WMD: -0.08 mmol/L, 95% CI: -0.22 to 0.07, p = 0.30). For HbA1c, the meta-analysis of three RCTs showed a marginally significant reduction (WMD: -1.63%, 95% CI: -3.36% to 0.11%, p = 0.06). The results of the meta-analysis on lipid profile showed a decreasing trend, although this reduction was not statistically significant for TC (WMD: -0.11 mmol/L, 95% CI: -0.30% to 0.08%, p = 0.27) or TG (WMD: -0.07 mmol/L, 95% CI: -0.32% to 0.19%, p = 0.62). However, a significant change in TG was reported in trials with a crossover design and RCTs with 4 weeks of intervention or less. Although HDL level did not show any significant change (WMD: -0.02 mmol/L, 95% CI: -0.10% to 0.07%, p = 0.70), the meta-analysis of five RCTs evaluating the long-term effects of bilberry supplementation revealed a significant change in LDL following bilberry supplementation (WMD: 0.07 mmol/L, 95% CI: 0.01%-0.14%, p = 0.01). Furthermore, no significant reduction was observed in SBP (WMD: -2.75 mmHg, 95% CI: -6.38% to 0.89%, p = 0.13) or DBP (WMD: -1.00 mmHg, 95% CI: -4.66% to 2.65%, p = 0.59) after bilberry supplementation. Finally, anthropometric indices including body weight (WMD: 0.04 Kg, 95% CI: -0.44% to 0.53%, p = 0.86) and inflammatory and oxidative stress markers including hs-CRP (WMD: -8.22 mg/L, 95% CI: -20.24% to 3.81%, p = 0.18), IL-6 (WMD: -7.19 pg/mL, 95% CI: -19.01% to 4.63%, p = 0.23), uric acid (WMD: -0.01 mmol/L, 95% CI: -0.03% to 0.01%, p = 0.36), and FRAP (WMD: -42.03 μmol/L, 95% CI: -100.54% to 16.48%, p = 0.16) showed no significant change after bilberry supplementation. Bilberry supplementation may have beneficial effects on HbA1c and TG, but not other cardio-metabolic indices. Therefore, long-term and high-quality trials are needed to confirm the promising effects of bilberries.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4094-4115"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compounds of Plant Origin: The Blue Ocean of Anti-Helicobacter pylori Medicines.","authors":"Huimin Wu, Qiang Song, Ye Wang, Rakia Manzoor, Xiaojun Yang, Xuegang Li, Xiaoli Ye, Hang Ma","doi":"10.1002/ptr.70031","DOIUrl":"10.1002/ptr.70031","url":null,"abstract":"<p><p>Helicobacter pylori (H. pylori), a globally prevalent pathogen implicated in gastritis, peptic ulcers, and gastric malignancies, remains a critical public health challenge due to its high infection rate and complex pathogenesis. Although antibiotic-based regimens are the current therapeutic mainstay, their clinical utility is increasingly constrained by rising resistance rates, treatment-associated adverse effects, and incomplete eradication efficacy. Natural products, particularly plant-derived bioactive compounds, have emerged as a promising reservoir for anti-H. pylori drug discovery, demonstrating multifaceted mechanisms ranging from direct bactericidal activity to virulence factor suppression. However, to date, no phytochemical compounds have been successfully developed into antibacterial drugs, though accumulating preclinical evidence highlights their translational potential. This review systematically evaluates the epidemiological characteristics and clinical impacts of H. pylori infection, as well as the therapeutic limitations of current eradication regimens. Furthermore, it emphasizes the current status, underlying mechanisms, and challenges of natural products in the treatment of H. pylori. We aim to gain deeper insights into the medicinal value of natural products, thereby providing valuable references for the development of novel drugs targeting H. pylori infection and evidence-based antimicrobial treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4282-4307"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytotherapy for Obesity Management: The Role of Gut Microbiota in Reshaping Adipose Tissue.","authors":"Huiyang Wang, Dongfang Zhang, Long Cheng","doi":"10.1002/ptr.70066","DOIUrl":"10.1002/ptr.70066","url":null,"abstract":"<p><p>People with obesity exhibit abnormal fat accumulation, systemic chronic inflammation, insulin resistance, hepatic steatosis, and dysregulation of glucolipid metabolism. However, interventions aimed at lifestyle modification and energy intake reduction have shown limited effectiveness. Adipose tissue is widely distributed throughout the body and has high plasticity. Reshaping adipose tissue, including activating brown adipose tissue and promoting the browning of white adipose tissue, can effectively enhance energy expenditure, thereby contributing to anti-obesity effects. Recent advancements in next-generation sequencing technology and metabolomics have provided deeper insights into the intricate relationship between gut microbiota and host metabolism. Phytotherapy has emerged as a promising approach to combat obesity, offering a relatively safe, cost-effective, and accessible alternative to traditional treatments. This review aims to explore the mechanisms through which phytotherapy-encompassing Chinese herbal medicine, herbal formulas, dietary plants, and functional foods-modulates gut microbiota and reshapes adipose tissue, thereby exerting anti-obesity effects. We included peer-reviewed original articles, which investigate phytotherapy's effects on modulating gut microbiota and reshaping adipose tissue. The outcome measures of the articles should involve parameters related to anti-obesity effects, such as body weight, body mass index, blood lipid levels, fasting blood glucose, insulin resistance index, and so on. Notably, current research primarily focuses on preclinical studies, indicating an urgent need for high-quality clinical trials to validate the actual efficacy of phytotherapy in obesity management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4247-4281"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oridonin Ameliorates Metabolic-Dysfunction-Associated Fatty Liver Disease by Inhibiting PANoptosis via Modulating SIRT2/NLRP3 Pathway.","authors":"Zimeng Wang, Yi Sun, Changyuan Wang, Jialin Yao, Ru Hao, Yang Wang, Huijun Sun","doi":"10.1002/ptr.70055","DOIUrl":"10.1002/ptr.70055","url":null,"abstract":"<p><p>Metabolic associated fatty liver disease (MAFLD) is the leading cause of chronic liver disease worldwide. Various studies have demonstrated that traditional Chinese medicine alleviates MAFLD by suppressing PANoptosis. Although Oridonin (ORI) is a traditional Chinese medicine that has been used in hepatosteatosis, its underlying mechanism for treating MAFLD, especially regarding PANoptosis, remains unclear. Therefore, this study aims to investigate the ameliorative effects of ORI on MAFLD by inhibiting PANoptosis and to elucidate the underlying mechanisms. A vivo model of MAFLD was constructed by feeding mice with a high-fat diet (HFD) for 12 weeks. ORI was simultaneously intragastric gavaged for 12 weeks. A vitro model of MAFLD was constructed by palmitic acid (PA) induced AML12 cells for 24 h; ORI was simultaneously induced for 24 h. Extraction of mice plasma for detecting lipid-related and oxidative stress-related assay kits was performed. Lipid metabolism and PANoptosis-related proteins and pathways were validated both in vivo and in vitro through western blotting and immunofluorescence. The functions of the candidate proteins were further investigated using the plasmid transfection technique. Then the Biotin labeling assays were used to analyze the proteins' direct interaction with ORI. ORI treatment significantly alleviated HFD-induced inflammation and PANoptosis. Likewise, ORI effectively attenuated PANoptosis induced by PA in the AML12 cells. Additionally, over-expression of NLRP3, which is a key component in PANoptosis, could partly antagonize the inhibiting effects of ORI on steatosis and PANoptosis. Next, our findings demonstrated the increased NLRP3 acetylation level in PA-induced cells, while ORI treatment decreased the NLRP3 acetylation level. Further studies revealed that ORI could bind to and activate SIRT2 to increase the protein expression and stability of SIRT2, which in turn deacetylated and inactivated NLRP3. Moreover, over-expression of NLRP3 could partly antagonize the inhibiting effects of ORI on lipid droplet deposition and PANoptosis, which could be rescued by over-expression of SIRT2. Therefore, these findings show that ORI can alleviate MAFLD by suppressing PANoptosis via inhibiting the SIRT2/NLRP3 pathway. These findings provide new therapeutic targets and mechanisms for the treatment of MAFLD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4181-4198"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Shogaol Reduces Renal Macrophage Infiltration by Targeting the STING Pathway to Alleviate Cisplatin Induced Renal Injury.","authors":"Xuewei Yan, Jiaojiao Luo, Xia Chen, Lixin Wang, Zihang Xu, Chunrong Guo, Weirong Zhu, Yue Ding, Jiaye Jiang","doi":"10.1002/ptr.70053","DOIUrl":"10.1002/ptr.70053","url":null,"abstract":"<p><p>Cisplatin is a widely used chemotherapeutic agent, but its dose-limiting nephrotoxicity remains a major clinical challenge. 6-Shogaol, a bioactive compound with potent anti-inflammatory and antioxidant properties, exhibits strong binding affinity for STING-a key mediator in cisplatin-induced kidney injury. This study aims to investigate the renoprotective effects of 6-shogaol against cisplatin nephrotoxicity and elucidate its underlying mechanisms. Using a murine model of cisplatin-induced nephrotoxicity and in vitro experiments with HK-2 cells, we evaluated the cytoprotective effects of 6-shogaol. Molecular docking simulations confirmed its high binding affinity for STING. A comprehensive approach, including flow cytometry, RNA sequencing, ELISA, qPCR, histopathological staining (H&E staining), immunofluorescence, and Western blot analyses, was employed to assess renal function, tubular injury, inflammatory responses, and molecular mechanisms. CRISPR/Cas9-mediated STING knockout was performed to validate the mechanistic role of STING. 6-Shogaol significantly attenuated cisplatin-induced renal damage, as evidenced by reduced serum creatinine and blood urea nitrogen levels, diminished macrophage infiltration, and downregulated expression of CCL2 and CCL5 in renal tissues. Molecular docking revealed stable binding between 6-shogaol and STING. In vitro, 6-shogaol mitigated cisplatin-induced cellular injury, suppressed the cGAS-STING pathway, and reduced pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) and chemokine (CCL2, CCL5) expression. STING knockout in HK-2 cells abolished cisplatin-induced cytotoxicity and attenuated the protective effects of 6-shogaol. These findings demonstrate that 6-shogaol alleviates cisplatin-induced kidney injury by targeting STING, thereby inhibiting CCL2/CCL5-mediated macrophage infiltration and subsequent inflammation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4081-4093"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic and Ethnobotanical Review of Ashwagandha's (Withania Somnifera) Teratogenic and Abortifacient Potentials.","authors":"Mark J Tallon, Igor Koturbash, Jason L Blum","doi":"10.1002/ptr.70079","DOIUrl":"https://doi.org/10.1002/ptr.70079","url":null,"abstract":"<p><p>Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been widely used in Ayurvedic medicine for its adaptogenic properties and therapeutic potential and has been investigated for its benefits related to sleep and stress management by Western medicine. However, concerns regarding its teratogenic and abortifacient effects have emerged following reports from the World Health Organization (WHO) and regulatory bodies. This systematic and ethnobotanical review critically evaluates these claims by assessing ashwagandha's toxicokinetics, toxicodynamics, and available safety data. A comprehensive literature review following PRISMA guidelines was conducted to identify studies on its reproductive toxicity, molecular interactions, and traditional usage. Historical ethnobotanical reports suggest potential abortifacient effects, but citation distortion and lack of primary source validation raise concerns regarding the validity of such claims. Toxicological studies in animal models demonstrate high tolerability, with no significant reproductive toxicity observed at doses relevant to human consumption. Human clinical studies also show no adverse effects on thyroid function, hormonal balance, or reproductive health. Altogether, evidence supporting significant teratogenic or abortifacient activity remains inconclusive. This review highlights the need for standardized, high-quality research addressing fertility and developmental outcomes in controlled conditions. Given the widespread use of ashwagandha as a dietary supplement ingredient and traditional medicine, a balanced and evidence-based approach is required to assess its safety, ensuring that regulatory actions are informed by robust scientific data rather than historical speculation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Apoptotic Inhibition of Colorectal Cancer Proliferation by Sclareol via Ferroptosis Involving SLC7A11/GPX4 Modulation.","authors":"Yu-Xi Li, Yuan Wu, Qiong Li, Yu-Qing Huang, Ying-Ying Yuan, Yan-Ni Su, Chien-Shan Cheng, Lan Zheng","doi":"10.1002/ptr.70010","DOIUrl":"https://doi.org/10.1002/ptr.70010","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent and lethal malignancy necessitating new treatments. Sclareol, the primary active component of Salvia sclarea L., exhibits diverse pharmacological properties, making it a promising anti-cancer drug warranting further investigation. To evaluate Sclareol's action in CRC cell death, various methods were performed, including cell viability and colony formation assays, EdU assay, flow cytometry for cell cycle analysis and apoptosis, as well as TUNEL staining, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, and Fe²⁺ fluorometric assay. RNA sequencing and pathway analysis, combined with in silico molecular docking, and immunoblotting, were conducted to determine the mechanism of action of Sclareol. A CRC xenograft model in immunocompetent mice was used to evaluate Sclareol's in vivo efficacy and toxicity, with immunohistochemistry confirming its mechanism of action. Sclareol significantly suppressed CRC cell proliferation and induced cell cycle arrest in vitro without significantly inducing apoptosis. Ferroptosis as a promising mechanism of action was validated through TEM, ROS detection, and Fe²⁺ staining. RNA sequencing analysis revealed enrichment in metal ion-transporter activity. Molecular docking analysis showed direct binding of Sclareol to the key ferroptosis-related target solute carrier family 7 member 11 (SLC7A11). Additionally, Sclareol downregulated the expression of SLC7A11, nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4) proteins, indicating ferroptosis induction in vitro. Significant tumor growth inhibition was observed without hepatic or renal toxicities, with immunohistochemistry confirming the suppression of ferroptosis- and proliferation-related markers in vivo. Sclareol inhibits CRC growth by modulating the ferroptosis pathway through the SLC7A11/GPX4 axis. Sclareol shows promise as a therapeutic agent in CRC, warranting further pre-clinical studies to confirm its efficacy and safety.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}