Phytotherapy Research最新文献

{"title":"A Review on Antifungal Activity of Plant Essential Oils.","authors":"Kai Li, Jianbo Guo, Ruiping Liang, Xuan Wang, Qin Chen, Jinhui Wang, Xiaoxiao Ge, Chao Chen, Jing Sun, Chongbo Zhao, Huanxian Shi, Rongxia Qiao, Xiaofei Zhang","doi":"10.1002/ptr.70038","DOIUrl":"10.1002/ptr.70038","url":null,"abstract":"<p><p>Fungal infections pose a significant threat to human health, crop production, and food safety. Concurrently, traditional antifungal drugs face challenges such as increasing drug resistance and adverse side effects, creating an urgent need for safer and more efficient therapeutic alternatives. Although significant progress has been made in researching the antifungal activity of plant essential oils (PEOs) in recent years, existing literature primarily focuses on the antifungal effects of individual essential oils (EOs) or their constituents, lacking systematic exploration and summarization of active components, mechanisms of action, and application approaches. Therefore, this review provides a comprehensive overview of the sources of PEOs, their antifungal activities, antifungal active components, mechanisms of action, and application methods (such as drug delivery systems and synergistic effects), aiming to enhance the bioavailability of PEOs. Finally, this review discusses the potential toxicity of PEOs and highlights the need for high-quality studies to systematically evaluate their clinical efficacy and safety in treating fungal infections. By systematically integrating existing research advances, it aims to provide valuable insights for future research directions and promote the widespread application of PEOs in antifungal research.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3736-3761"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601225","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":"Geniposide Improves Glycolysis Driven Angiogenesis in Experimentary Arthritis by Inhibiting SphK1-PI3K-Akt-PFKFB3 Signal.","authors":"Yanhong Bu, Hong Wu, Ran Deng, Yan Wang, Peirong Gan, Xintong Dong, Jiangtao Ke","doi":"10.1002/ptr.70019","DOIUrl":"10.1002/ptr.70019","url":null,"abstract":"<p><p>Angiogenesis driven by aerobic glycolysis in endothelial cells sustains rheumatoid arthritis (RA) progression. Geniposide (GE), an iridoid ether extracted from the Rubiaceae plant Gardenia jasminoides J. Ellis, has shown anti-angiogenic potential in experimental arthritis. However, its role in metabolic regulation of angiogenesis remains unclear. The purpose was to explore the roles of GE on metabolism in angiogenesis and potential mechanisms. Adjuvant arthritis (AA) rat models and human umbilical vein endothelial cells (HUVECs) were established. Network pharmacology predicted potential targets of GE, while metabolomics analysis was conducted on RA patient serum and AA rat synovial tissue. The role of PFKFB3, a key glycolytic enzyme, was validated by gene silencing and pharmacological interventions. The signaling axis was further explored using inhibitors, agonists, and protein interaction assays. The role of the key glycolytic enzyme PFKFB3 and the upstream-downstream relationship of the signaling axis were validated through gene silencing and pharmacological intervention. GE improved angiogenesis in vivo and in vitro models, and PFKFB3 may be a potential target. Metabolomics has shown that GE significantly inhibited the elevated levels of glycolysis metabolism in arthritis rats, which may be related to the inhibition of PFKFB3 expression. PFKFB3-siRNA down-regulated angiogenesis in HUVECs, demonstrating that PFKFB3-mediated glycolysis was involved in angiogenesis. SphK1-siRNA indicated that PFKFB3 was regulated and activated by the SphK1-PI3K-AKt signal and induced a high level of glycolytic metabolism phenotype. GE intervention significantly downregulated the levels of glycolysis metabolism in arthritis models by inhibiting the SphK1-PI3K-AKt-PFKFB3 signal. The SphK1-PI3K-Akt-PFKB3 signal is the metabolic mechanism of the natural product active ingredient GE in anti-angiogenesis, revealing the important role of glycolytic metabolism in RA angiogenesis. This provides new insights into metabolic regulation in RA treatment and potential therapeutic strategies for metabolic targeted interventions.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3419-3431"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529279","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":"Dihydrotanshinone I Targets PGAM1 to Induce SYVN1-Mediated Ubiquitination and Suppress Glycolysis in Hepatocellular Carcinoma.","authors":"Ru Xu, Jiawei Dai, Ruijie Gong, Ruoxin Tu, Qiaozi Wang, Hongdan Zheng, Li Zhou, Shusheng Wang, Jiabin Cai, Haixiang Sun, Pingting Gao, Pengfei Gao","doi":"10.1002/ptr.70017","DOIUrl":"10.1002/ptr.70017","url":null,"abstract":"<p><p>Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme frequently overexpressed in hepatocellular carcinoma (HCC), contributing to tumor progression through aberrant glycolysis. Dihydrotanshinone I (DHT), a bioactive natural compound derived from Salvia miltiorrhiza , has been proposed as a potential therapeutic agent for HCC. This study aims to characterize DHT as a PGAM1-targeting agent and investigate its anti-HCC effects. We assessed the effects of DHT on PGAM1 regulation and glycolytic activity in vitro and in vivo. Using proteasomal degradation assays, we evaluated the role of Synoviolin 1 (SYVN1), an E3 ubiquitin ligase, in mediating the ubiquitination and degradation of PGAM1. The impact of DHT on key glycolytic enzymes, glucose consumption, lactate production, and ATP levels was also measured. In vivo, orthotopic and subcutaneous xenograft HCC models were used to evaluate tumor growth suppression following DHT treatment. DHT induced SYVN1-mediated K48-linked polyubiquitination and proteasomal degradation of PGAM1, disrupting glycolytic flux by reducing hexokinase and pyruvate kinase activities, decreasing glucose consumption, lactate production, and ATP levels. In vivo, DHT demonstrated dose-responsive tumor suppression without observable short-term toxicity. These findings establish DHT as a promising therapeutic agent for HCC by targeting PGAM1 degradation and disrupting glycolysis. The study provides a mechanistic framework for developing plant-derived therapeutics targeting metabolic pathways in liver cancer.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3762-3783"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609056","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":"IL-23 Receptor Agonism by Mulberroside C Activates the RASGRP1/RAS/ERK Pathway Contributing to Leukopenia Treatments.","authors":"Lin-Wei Zhang, Yuan-Zhi Liu, Tian-Ci Li, Jian-Yue Li, Xu-Yan Yan, Zhi-Xuan Liu, Lu-Yao Li, Hong-Ping Shen, Wen-Jun Zou, Jian-Ming Wu","doi":"10.1002/ptr.70026","DOIUrl":"10.1002/ptr.70026","url":null,"abstract":"<p><p>Chemotherapy- and radiotherapy-induced leukopenia is a common challenge in cancer treatment, with a significant dearth of effective therapeutic options. IL-23 receptor (IL-23R) signaling holds the potential for promoting neutrophil generation and maturation, yet the underlying mechanisms remain elusive. This study investigates the molecular mechanism and efficacy of Mulberroside C (MC) in alleviating leukopenia via IL-23R signaling. In vitro, flow cytometry, nitroblue tetrazolium reduction assay, and Giemsa staining were employed to evaluate MC's impact on neutrophil differentiation in NB4 and HL-60 cell lines. The antibacterial activity of MC was assessed using an agar plate assay. In vivo, leukopenia models induced by irradiation and cyclophosphamide were established in zebrafish and mice to determine MC's effect on neutrophil recovery. Mechanistic studies involved RNA sequencing, network pharmacology analysis, molecular docking, quantitative real-time PCR (qRT-PCR), and Western blotting to explore the associated signaling pathways. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to identify MC's targets. MC significantly enhanced neutrophil maturation in a dose-dependent manner, facilitating leukopenia recovery. Mechanistically, MC binds to IL-23R, upregulating G-CSF, GM-CSF, and RASGRP1 and activating the RAS/ERK signaling pathway. Notably, the upregulation of RASGRP1 by MC supports the generation of fully functional neutrophils, compared to those induced by G-CSF and GM-CSF alone. This study provides the first evidence that MC promotes neutrophil generation and antimicrobial activity through the IL-23R-mediated pathway, offering a promising therapeutic strategy for leukopenia.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3578-3600"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576110","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":"Potential Candidates of Natural Antioxidants From Herbs for Treating Lung Disorders: Focus on Redox Balance and Natural Products.","authors":"Xing Chang, Siyuan Zhou, Zhaoqi Yan, Qin Zhang, Jinfeng Liu, Yanli Wang, Xuanke Guan, Qiaomin Wu, Ruxiu Liu","doi":"10.1002/ptr.70008","DOIUrl":"10.1002/ptr.70008","url":null,"abstract":"<p><p>Oxidative stress (OS) refers to an imbalance between oxidation and antioxidation processes. Reactive oxygen species (ROS) are normal byproducts of redox reactions occurring in vivo. When there is an overproduction of ROS or an insufficient antioxidant capacity, ROS accumulate in airway tissues and alveolar cells, potentially inducing OS. This condition can cause the migration and accumulation of activated inflammatory cells in the pulmonary microcirculation, airways, and alveoli, further enhancing lung inflammatory responses and triggering an inflammatory cascade. Inflammation inevitably results in pulmonary tissue damage and remodeling, leading to pulmonary diseases. Since the discovery of artemisinin, a malaria inhibitor, by Nobel laureate Youyou Tu, the effects of natural antioxidants on pulmonary diseases have been extensively evaluated. Recently, many active components of natural antioxidants have been shown to be effective in modulating redox imbalances in alveolar, endothelial, and tumor cells. Therefore, the supplementation of natural antioxidants may be an effective strategy to mitigate asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and lung cancer. This paper reviews the advances in natural antioxidants for protecting against various pulmonary diseases by regulating redox imbalance. Antioxidants offer unique advantages and substantial potential.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3353-3385"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529292","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":"Formononetin From Sophora flavescens Aiton Alleviates Atopic Dermatitis by Suppressing Neutrophil Extracellular Traps.","authors":"Lin Cheng, Zhirui Du, Xueqiao Yan, Manju Che, Guoguo Zhi, Xiuying Ma, Funeng Geng, Baojie Li","doi":"10.1002/ptr.70020","DOIUrl":"10.1002/ptr.70020","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited effective treatment. Sophora flavescens Aiton (Kushen) exhibits anti-inflammatory properties, but its key active components and mechanisms against AD remain unclear. This study aimed to identify its therapeutic compounds and the underlying molecular mechanisms. Network pharmacology and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry were applied to screen for the potential bioactive compounds from Kushen, which were validated in AD mouse models. Formononetin (FMN) was topically administered to evaluate its curative efficacy through histopathological and immunofluorescent staining of skin lesions. Transcriptomic profiling explored the molecular mechanisms, with subsequent validation of neutrophil extracellular traps (NETs)-associated markers by immunofluorescent staining and western blotting. Co-treatment with PAD4 inhibitor GSK484 and molecular docking were used to study the underlying mechanisms. The study identified FMN as an important active component in Kushen, which showed therapeutic effects comparable to dexamethasone in AD models. FMN normalized cutaneous hyperplasia, reduced infiltration of CD3⁺ T cells, mast cells, and neutrophils, and suppressed inflammatory cytokine expression. Mechanistically, FMN inhibited NETs formation evidenced by decreased levels of citrullinated histone H3 (citH3), myeloperoxidase (MPO), and peptidylarginine deiminase 4 (PAD4). GSK484 co-treatment showed non-synergistic effects, suggesting that FMN suppresses NETs formation primarily through PAD4/MPO inhibition, which was confirmed by molecular docking. These findings highlight FMN as a primary anti-AD constituent of Kushen, therapeutically suppressing NETs-driven crosstalk of innate and adaptive immunity. FMN's multitarget mechanisms provide mechanistic insights and position it as a candidate for AD treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3784-3799"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601227","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":"Phytochemicals as Modulators of NETosis: A Comprehensive Review on Their Mechanisms and Therapeutic Potential.","authors":"Fatemeh Askarizadeh, Sercan Karav, Amirhossein Sahebkar","doi":"10.1002/ptr.70025","DOIUrl":"10.1002/ptr.70025","url":null,"abstract":"<p><p>Medicinal plants have a longstanding history in the treatment of various diseases, including infectious and inflammatory disorders. These therapeutic effects are attributed to the presence of bioactive compounds. Among these, phytochemicals, particularly polyphenols such as curcumin, luteolin, resveratrol, alkaloids, and terpenoids, play a significant role as a secondary metabolites with potent NETosis-modulating properties. Phytochemicals include a wide range of bioactive substances with various therapeutic properties, including anti-inflammatory, antibacterial, anticancer, anti-metastatic, and antioxidant effects. These compounds specifically target NETosis in inflammatory and autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, psoriasis, and cancer. In such conditions, unregulated inflammatory responses lead to complications and disease progression. Innate immunity and neutrophils are recognized as the primary constituents of the immune response. NETosis is a process associated with neutrophils in the inflammatory response, which is initiated to eliminate pathogens; however, as it is dysregulated, it results in tissue damage. This process is initiated in order to eliminate external factors and modulate inflammatory pathways. However, excessive activation of NETosis leads to tissue damage and exacerbates inflammation. The phytochemicals discussed herein modulate NETosis through distinct mechanisms, including inhibiting or reducing key mediators such as MPO, NE, and ROS. This study provides the first comprehensive review systematically evaluating the active phytochemicals effect in the treatment of various diseases, with a special focus on their NETosis-modulating effects. We highlight their specific mechanism of action against NETotic pathways and clinical potential as targeted therapies for NET-driven disease.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3545-3577"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567695","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":"Unveiling the Molecular Mechanisms of Natural Triterpenoids From Mushrooms Against Type 2 Diabetes: A Critical Review.","authors":"Nidesha Randeni, Jinhai Luo, Baojun Xu","doi":"10.1002/ptr.70030","DOIUrl":"10.1002/ptr.70030","url":null,"abstract":"<p><p>The exploration of triterpenoids derived from medicinal mushrooms presents an emerging frontier in managing type 2 diabetes (T2D). Triterpenoids achieve their therapeutic potential by targeting multiple pathways implicated in T2D pathology, including insulin resistance, chronic inflammation, and oxidative stress. This review critically summarizes the mechanisms by which mushroom-derived triterpenoids, such as ganoderic acid, betulinic acid, and pachymic acid, exert anti-diabetic effects. The molecular mechanisms of triterpenoids derived from medicinal mushrooms include the activation of AMP-activated protein kinase (AMPK) and phosphatidylinositol 3kinase (PI3K-Akt) signaling pathways, enhancing insulin sensitivity and glucose uptake, as well as the inhibition of α-glucosidase activity, thereby reducing postprandial hyperglycemia. Additionally, triterpenoids can alleviate insulin resistance and pancreatic β-cell dysfunction through modulating oxidative stress and inflammation. Notably, triterpenoids influence gut microbiota composition, promoting a healthier microbial balance that supports glucose metabolism and overall metabolic health. While preclinical studies underscore the promising potential of triterpenoids in T2D intervention, further high-quality clinical trials are needed to validate the mushroom-derived triterpenoids' clinical efficacy firmly. This review synthesizes these findings to establish a comprehensive framework for further research and product development of medical mushrooms.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3466-3485"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560797","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":"Targeting CDK9 With Harmine Induces Homologous Recombination Deficiency and Synergizes With PARP Inhibitors in Ovarian Cancer.","authors":"Hao Zhang, Xiaomei Luo, Shiwei Li, Yingjie Wang, Yutong Gao, Yaodi Shao, Haixia Huang, Jindan Sheng, Xiu Tian, Fang Bai, Gaofeng Fan, Renhao Xue, Yu Wang","doi":"10.1002/ptr.70021","DOIUrl":"10.1002/ptr.70021","url":null,"abstract":"<p><p>Ovarian cancer patients with homologous recombination (HR) proficiency are more likely to develop resistance to poly (ADP-ribose) polymerase (PARP) inhibitors, resulting in poor prognosis. Harmine, a natural compound with verified clinical safety, is a potential inhibitor of HR activity. However, its effect on HR has not been tested in ovarian cancer. More importantly, its specific target involving the HR pathway is still unknown. A fluorescent reporter cell system was employed to assess the HR efficiency of cells treated by harmine. The target of harmine in the HR pathway was identified via a molecular docking screening in silico and confirmed using a cellular thermal shift assay. Evaluation of harmine treatment combined with the PARP inhibitor olaparib in BRCA1/2 wild-type ovarian cancer was performed. Treatment with harmine inhibited HR activity in a dose-dependent manner in ovarian cancer cells and selectively suppressed HR-proficient cells with high replication stress, marked with CCNE1 amplification. HR-related protein cyclin-dependent kinase 9 (CDK9) was identified as the target of harmine. Specifically, harmine diminished the interaction of CDK9 with cyclin T, resulting in impaired formation of the p-TEFb complex and subsequent transcription elongation. Hence, harmine downregulated the transcription of key HR-related genes. Moreover, harmine synergized with PARP inhibitor olaparib in BRCA1/2 wild-type ovarian cancer. Harmine inhibits HR repair by interfering with CDK9-mediated transcription elongation for HR-related genes, thus enhancing the potency of olaparib, providing a promising therapeutic strategy to improve the prognosis of HR-proficient ovarian cancer patients.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3648-3663"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591965","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":"Scutebarbatine B Exerts Anti-Breast Cancer Activity by Inducing Cell Cycle Arrest and Apoptosis Through Multiple Pathways.","authors":"Chong Niu, Ruo-Tong Li, Xiao-Shan Hao, Xiao Qi, Feng-Ze Wang, Hong-Rong Fei","doi":"10.1002/ptr.70007","DOIUrl":"10.1002/ptr.70007","url":null,"abstract":"<p><p>Breast cancer is the most commonly occurring cancer among women with high mortality. Identifying effective anticancer compounds to improve the overall survival is imperative. The present study was designed to evaluate the effects and underlying mechanisms of Scutebarbatine B (SBT-B), a diterpenoid alkaloid extracted from Scutellaria barbata D. Don ( S. barbata ), on breast cancer. Cell viability assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, immunofluorescence, flow cytometry analysis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, Western blot analysis, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and dihydroethidium (DHE) staining were performed to elucidate the anticancer mechanisms of SBT-B in vitro. Mice xenograft models were used to assess the anticancer properties in vivo. We demonstrated that SBT-B suppressed the proliferation of breast cancer cells in a dose-dependent manner. SBT-B treatment induced DNA damage response, G2/M phase arrest and downregulated the expression of cyclinB1, cyclinD1, Cdc2, and p-Cdc2. SBT-B could trigger apoptosis through increasing the cleavage of caspase-8, caspase-9 and PARP in breast cancer cells. Additionally, SBT-B elevated the generation of intracellular reactive oxygen species (ROS). Treatment with a ROS scavenger N-acetyl cysteine (NAC) partially blocked viability reduction and cleavage of caspase-8 and PARP induced by SBT-B. Moreover, SBT-B blocked pRB/E2F1 and Akt/mTOR pathways. Incubation with SBT-B increased the expression of IRE1 and phospho-JNK. In vivo, SBT-B exhibited significant suppression of tumor growth in xenograft models. We demonstrate firstly that SBT-B induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells. ROS generation, suppression of oncogenic signaling and activation of IRE1/JNK pathway play an essential role in the anticancer activity of SBT-B. Our study highlights the potential of SBT-B as an alternative candidate to treat human breast cancer.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3432-3449"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529293","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}