Phytotherapy Research最新文献

{"title":"Current Insights of the Potential Plant Bioactive Compounds on Modulating the mTOR Signaling Pathway in Regulating Oncological Disorders.","authors":"Sonali Khanal, Manjusha Pillai, Md Shimul Bhuia, Muhammad Torequl Islam, Onkar Sharma, Rachna Verma, Eugenie Nepovimova, Kamil Kuca, Dinesh Kumar, Raihan Chowdhury","doi":"10.1002/ptr.70051","DOIUrl":"10.1002/ptr.70051","url":null,"abstract":"<p><p>Deregulation of the mechanistic target of the rapamycin (mTOR) pathway plays an important role in cancer genesis and progression, making it an attractive target for cancer treatment. Disrupting the mTOR pathway contributes to uncontrolled cell growth, increased proliferation, and enhanced cell survival, all of which are hallmarks of cancer. The findings imply that the deregulation of the mTOR pathway in cancer provides a compelling basis for therapeutic treatments. Phytochemicals such as flavonoids and polyphenols have been shown to play a key role in suppressing different kinases implicated in PI3K/AKT/mTOR signaling cascades. A thorough study of the molecular connections between bioactive substances, mTOR signaling, and autophagy activation can lead to the creation of personalized treatments that work better and have fewer side effects. Finding out how important it is to target the mTOR pathway and how to use bioactive chemicals from plants to treat cancer are both important discoveries that could lead to more precise medicine and the development of effective cancer drugs. Finally, targeting mTOR pathways using plant-derived chemicals may be a promising therapy strategy for cancer. This review tries to summarize putative plant bioactive chemicals that act on malignancies via mTOR signaling pathways. Furthermore, the paper discusses the role of the mTOR pathway in cancer, specifically its influence on cell growth, proliferation, and survival.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4046-4059"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732693","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":"Daidzin Inhibits Endoplasmic Reticulum Stress by Regulating FoxO1 Expression to Alleviate Osteoarthritis Progression.","authors":"Kaiye Chen, Yangcan Jin, Hao Chen, Luyi Jiang, Xianpeng Chen, Hanwen Zhang, Yuzhe Lin, Yangbo Li, Heng Yu, Zhongke Lin","doi":"10.1002/ptr.70081","DOIUrl":"https://doi.org/10.1002/ptr.70081","url":null,"abstract":"<p><p>Endoplasmic reticulum stress (ERS) and chondrocyte apoptosis are recognized as critical pathological factors in the development of osteoarthritis (OA). Daidzin (DDZ), an isoflavone derived from soybean, exhibits antioxidant, anticancer, and anti-atherosclerotic properties. This research seeks to investigate the therapeutic potential and primary mechanisms of Daidzin using a murine Destabilization of the Medial Meniscus instability model and a TBHP-induced in vitro OA chondrocyte model. Through network pharmacology analysis, potential OA-related targets of Daidzin were identified. A mouse OA model was established and randomly divided into five groups: sham operation group, DMM group, DMM + 5 mg/kg DDZ group, DMM + 10 mg/kg DDZ group, and DMM + 3 mg/kg indomethacin group, which were examined histologically by hematoxylin and eosin (HE), Safranine O (SO), and histochemistry, and histologically by X-ray and CT techniques Imaging. The effect of Daidzin on chondrocyte endoplasmic reticulum stress, apoptosis, extracellular matrix (ECM) breakdown, and Forkhead Box O1 (FoxO1)-related signaling pathways was further investigated using various experimental techniques. The findings indicate that Daidzin upregulates FoxO1 level, inhibits endoplasmic reticulum stress, and attenuates both chondrocyte apoptosis and ECM degradation. The results suggest that Daidzin exerts therapeutic effects in OA models through both in vivo and in vitro experiments, highlighting its possibility as a viable treatment option for osteoarthritis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964986","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":"Recent Advances in the Investigation of the Role and Immunoregulatory Mechanisms of Polysaccharides From Traditional Chinese Medicine in the Intervention of Liver Cirrhosis.","authors":"Hemiao Cui, Haixia Ji, Lu Zhang, Wenwen Zhang, Ruixia Kang, Yan Ni, Xuliang Hao","doi":"10.1002/ptr.70045","DOIUrl":"10.1002/ptr.70045","url":null,"abstract":"<p><p>Cirrhosis is a severe chronic liver disease that typically develops as a result of prolonged hepatic injury and subsequent fibrosis, often driven by immune-mediated mechanisms, inflammatory responses, and oxidative stress. Polysaccharides derived from traditional Chinese medicine (TCM) are prominent constituents of herbal formulations widely employed in the management of cirrhosis and have demonstrated significant efficacy in alleviating clinical symptoms. This review aims to elucidate the potential roles and immunomodulatory mechanisms of TCM polysaccharides in the intervention of cirrhosis. A systematic search was conducted using PubMed and China National Knowledge Infrastructure (CNKI), with keywords including \"Traditional Chinese medicine polysaccharides,\" \"liver cirrhosis,\" and \"liver fibrosis,\" focusing primarily on studies published within the last 5 years. A limited number of foundational older references were also included. After screening for relevance, language (English/Chinese), and full-text availability, 104 articles were analyzed. Signaling pathways such as transforming growth factor-beta1 (TGF-β1)/Smads, mitogen-activated protein kinase (MAPK), nuclear transcription factor-kappaB (NF-κB), interleukin-22 (IL-22)/signal transducer and activator of transcription 3 (STAT3), and wingless-related integration site (Wnt)/β-catenin, as well as various cytokines, have been identified as critical in the progression of cirrhosis. TCM polysaccharides exert their therapeutic effects on cirrhosis through the modulation of immune mechanisms within hepatocytes, thereby inhibiting liver fibrosis, alleviating oxidative stress, and suppressing inflammatory responses. TCM polysaccharides exhibit substantial therapeutic potential for treating cirrhosis through their immunomodulatory effects. These findings indicate that TCM polysaccharides warrant further investigation and clinical translation to fully realize their potential in managing cirrhosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3903-3923"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643141","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 Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non-Small Cell Lung Cancer via Endoplasmic Reticulum-Stress Mediated Apoptosis.","authors":"Jia-Lu Lü, Jun Liang, Yi Zhang, Xue-Qing Liu, Wen-Fei Wang, Hai-Xue Kuang, Yong-Gang Xia","doi":"10.1002/ptr.70036","DOIUrl":"10.1002/ptr.70036","url":null,"abstract":"<p><p>Non-small cell lung cancer remains a significant global health challenge. The limited efficacy, drug resistance, and toxicity of current treatments highlight the need for novel therapeutics. While Panax quinquefolium L. has demonstrated anti-tumor activity in previous studies, the therapeutic potential of its small molecular weight saccharide fraction (SFPQ) remains unexplored. This study investigates the anti-tumor efficacy and mechanisms of SFPQ, aiming to establish its potential as a novel anti-cancer agent. SFPQ was isolated via macroporous resin adsorption and ultrafiltration, then characterized by LC-MS/MS analysis. In vitro cytotoxicity was assessed using CCK-8 and colony formation assays, and apoptosis was quantified via flow cytometry. Live-cell fluorescent labeling and confocal microscopy confirmed the specificity of SFPQ for the endoplasmic reticulum. Mechanistic insights into endoplasmic reticulum stress were elucidated via bioinformatics analysis, Western blot, and RT-qPCR assays. Lentiviral transduction and pharmacological inhibition validated SFPQ-mediated regulation of IRE1/JNK phosphorylation and c-Myc expression. In vivo anti-tumor efficacy and safety were assessed using xenograft models, complemented by morphometric parameters analysis and histopathology. CCK-8 and colony formation assay demonstrated cytotoxic effects of SFPQ on non-small cell lung cancer cells. SFPQ significantly promoted endoplasmic reticulum Ca²⁺ efflux, altered endoplasmic reticulum morphology, and increased the apoptosis rate for A549 cells. Live-cell imaging confirmed strong endoplasmic reticulum affinity, while mechanistic studies demonstrated that SFPQ triggered endoplasmic reticulum stress-mediated apoptosis via the IRE1/JNK/c-Myc axis. In xenograft models, SFPQ significantly reduced tumor volume and weight in a dose-dependent manner, showing comparable efficacy to cisplatin. Histopathological analysis further confirmed SFPQ's favorable safety profile. This study elucidates the endoplasmic reticulum stress-mediated anti-lung cancer mechanism of SFPQ through IRE1/JNK/c-Myc signaling. SFPQ exhibits potent anti-lung cancer activity in vitro and in vivo with minimal systemic toxicity, supporting its potential as a novel therapeutic agent.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3868-3885"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637729","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":"Modulation of miRNAs by Phytochemicals in Cerebral Ischemia: A Systematic Review of In Vitro and In Vivo Studies.","authors":"Joanna Rzemieniec, Mirko Marino, Benedetta Mercuriali, Laura Castiglioni, Paolo Gelosa, Majeda Muluhie, Cristian Del Bo', Patrizia Riso, Luigi Sironi","doi":"10.1002/ptr.70062","DOIUrl":"10.1002/ptr.70062","url":null,"abstract":"<p><p>Phytochemicals gained substantial interest for their protective action in cerebral ischemia. Additionally, there is a growing body of evidence suggesting that miRs play a role in stroke therapy. However, no systematic review to date has summarized the impact of phytochemicals on miRs modulation and their role in protecting the brain against ischemia. This systematic review aims to assess the current literature on the protective action of phytochemicals in cellular and animal models of stroke, with special focus on the miRs modulation. A literature search was conducted across three databases (PubMed, Scopus, Embase), adhering to PRISMA guidelines. Studies published in English between 2014 and 2024 were included based on relevant keywords. A total of 224 articles were excluded based on their title and/or abstract as they were deemed irrelevant. Furthermore, 4 articles were excluded due to the lack of an English or full-text version. Finally, 14 articles were included in this review. Phytochemicals reverted ischemia-induced changes in miRs expression; that is, they upregulated miR-556-3p, miR-223-3p, miR-1287-5p, miR-214, miR-96, miR-450b-5p, miR-149-5p, miR-375, and downregulated miR-145-5p, miR-124, miR-128-3p, miR-122, miR-181b, miR-155, miR-134, and miR-128-3p. These, in turn, led to an inhibition of apoptosis, inflammation, oxidative stress, ferroptosis, pyroptosis, and activation of Wnt and AMPK signaling. Our analysis indicates that targeting miRs with phytochemicals may inhibit the ischemic injury; thus, it represents a promising tool for the development of new therapeutic strategies for stroke. Given that all of the reviewed studies utilized cellular or animal models, further human clinical trials are necessary to confirm these findings.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4327-4347"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848265","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 Combination of Natural Products: A Promising Therapeutical Way for Management of Breast Cancers.","authors":"Pei-Pei Wang, Cheng-Xun He, Yang-Yang Shuai, Hai-Jun Zhang, Lei Zhang, Hui Ao, Wei Peng, Hong Zhang","doi":"10.1002/ptr.70044","DOIUrl":"10.1002/ptr.70044","url":null,"abstract":"<p><p>Breast cancer currently exhibits the highest incidence rate among gynecological malignancies worldwide. Natural products, which have been extensively utilized in antiviral therapies globally, demonstrate unique therapeutic advantages in breast cancer management through combinatorial applications. This article reviews recent advances in both the therapeutic effectiveness and underlying mechanisms of natural product combination therapy for breast cancer. These combinations simultaneously target multiple oncogenic pathways by inhibiting cellular proliferation and viability, suppressing autophagy and angiogenesis, blocking invasion and metastasis, and inducing cell cycle arrest and apoptosis. Beyond their direct anticancer effects, natural product combinations modulate immune responses and remodel the tumor microenvironment, offering novel therapeutic perspectives. However, rigorously designed clinical trials remain essential to validate the clinical efficacy of natural product-chemotherapeutic combinations in breast cancer treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3886-3902"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637742","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":"Embelin Mitigates the Impact of Perinatal Inflammation on Neuron Development by Inhibiting 5-Lipoxygenase-Mediated Ferroptosis.","authors":"Feng Zhang, Mengya Sun, Shiyi Ma, Junfang Sun, Yishi Li, Xianghong Li, Hong Jiang","doi":"10.1002/ptr.70052","DOIUrl":"10.1002/ptr.70052","url":null,"abstract":"<p><p>Neuronal development in newborns is often constrained by perinatal inflammation, with limited research available on the pathogenesis and treatment strategies for this condition. This study aimed to investigate the neuroprotective effects of Embelin in mitigating perinatal inflammation-induced neuronal development limitations by targeting 5-lipoxygenase (5-LOX) and reducing oxidative stress and ferroptosis. This study utilized in vivo and in vitro inflammation models to assess the therapeutic potential of Embelin, a small molecule drug from the FDA compound library. Using Autodock software and surface plasmon resonance detection technology, 5-LOX was identified as the molecular target of Embelin. Neuronal ferroptosis and oxidative stress were analyzed in rat models and PC12 cells treated with lipopolysaccharide (LPS) and Embelin. Biochemical assays, immunofluorescence staining, and western blotting were performed to quantify protein expression and oxidative stress markers. Embelin, along with the 5-LOX inhibitor Zileuton and 5-LOX mRNA silencing, significantly inhibited 5-LOX expression in neurons. Conversely, overexpressed 5-LOX promoted ferroptosis, and this effect could be inhibited by Embelin. These interventions reduced oxidative stress, suppressed ferroptosis, and promoted normal neuronal development in the cerebral cortex and hippocampus. The findings highlight Embelin's ability to specifically target and mitigate 5-LOX-induced ferroptosis, facilitating recovery from perinatal inflammation-induced neurodevelopmental deficits. Embelin demonstrates significant neuroprotective potential by inhibiting 5-LOX-mediated ferroptosis and oxidative stress, offering a promising therapeutic strategy for perinatal brain injury and related neurodevelopmental disorders.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4060-4080"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732726","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":"Insights Into Effects of Natural Bioactive Components on Inflammatory Diseases in Respiratory Tract.","authors":"Jincan Luo, Jinhai Luo, Zhonghao Fang, Yu Fu, Baojun Bruce Xu","doi":"10.1002/ptr.8367","DOIUrl":"10.1002/ptr.8367","url":null,"abstract":"<p><p>The increasing prevalence of inflammatory diseases in the respiratory tract worldwide has raised concerns, and due to its high prevalence and poor prognosis, it remains a clinical focus and research hotspot. These inflammatory diseases include airway inflammation, asthma, bacterial antigens-induced tonsil epithelial inflammation, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), COVID-19, acute lung injury, and lung cancer. This review summarizes the relevant molecular mechanisms of inflammatory diseases in the respiratory tract and the progress of natural bioactive components in inflammatory diseases in the respiratory tract. The natural bioactive components have good therapeutic or intervention effects on inflammatory airway diseases in vitro, in vivo, and in clinical trials. The information on inflammatory diseases in the respiratory tract and natural bioactive ingredients in anti-inflammatory diseases were collected from famous literature databases such as Web of Science, PubMed, and Google Scholar, with keywords including bioactive components, inflammatory diseases, respiratory tract, and so forth. The bioactive phytochemicals, such as curcumin, ginsenoside, safranal, melatonin, could improve inflammatory diseases through the regulation of PI3K/Akt, NF-κB, NRF2/HO-1, MAPK, cAMP-PKA, and MEK/ERK Signaling pathways. Further high-quality studies are still needed to firmly establish the clinical efficacy of bioactive ingredients. This review provides new insight for future research on functional food or drug-lead compound development on natural products improving inflammatory diseases in the respiratory tract.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4199-4229"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789712","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":"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}