Phytotherapy Research最新文献

{"title":"Herbal Therapeutics in Osteoporosis: Mechanisms, Evidence, and Translational Potential.","authors":"Elnaz Vafadar Moradi, Sina Vossoughinia, Zahra Yazdanpanah, Hossein Sobhani, Jalileh Jalali, Mahboobeh Ghasemzadeh Rahbardar","doi":"10.1002/ptr.70457","DOIUrl":"https://doi.org/10.1002/ptr.70457","url":null,"abstract":"<p><p>Osteoporosis is a chronic bone disease marked by reduced density and increased fracture risk. Current treatments face limitations in safety, efficacy, and long-term adherence, prompting interest in alternative therapies. Herbal medicine, with its bioactive compounds and historical use, offers potential for bone health support. This review explores the role of Chrysanthemum morifolium, Crocus sativus, Eriobotrya japonica, Ficus carica, Glycine max, Olea europaea, Salvia rosmarinus, and Zingiber officinale in preventing and managing osteoporosis. Relevant studies were identified through comprehensive searches of Google Scholar, PubMed, Scopus, and Web of Science, without time restriction up to October 2025. Included literature encompassed in vitro experiments, in vivo animal models, and clinical trials investigating herbal interventions targeting bone loss and osteoporosis-related mechanisms. The reviewed botanicals modulate key molecular pathways involved in bone remodeling, including RANKL/NFATc1, MAPKs, NF-κB, Sirt1, Nrf2, BMP/Smad, Wnt/β-catenin, and XPO5-microRNA axes. Their bioactive constituents exert antioxidant, anti-inflammatory, anti-apoptotic, anti-senescent, and hormone-modulating effects, collectively promoting osteoblast differentiation and suppressing osteoclastogenesis. Several agents, such as crocin, safranal, and ursolic acid, demonstrated dual-action profiles and favorable safety in preclinical models, with emerging evidence supporting their immunomodulatory and angiogenic roles. Herbal therapeutics offer a multi-targeted, biologically harmonious approach to osteoporosis management. This review provides a mechanistic synthesis and translational framework for future research, highlighting their potential as adjunctive therapies, especially in aging populations. Standardization, clinical validation, and interdisciplinary collaboration are essential to advance these botanicals from bench to bedside.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025761","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":"Plant-Derived Extracellular Vesicles: Biogenesis, Function, and Application in Cancer Immunotherapy.","authors":"Guosheng Li, Mengyu Li, Shujing Liu, Yuan Wei, Chen Wang","doi":"10.1002/ptr.70456","DOIUrl":"https://doi.org/10.1002/ptr.70456","url":null,"abstract":"<p><p>Plant-derived extracellular vesicles (PDEVs) are nanoscale, lipid bilayer-enclosed vesicles secreted by plant cells. They are widely distributed across plant tissues, including fruits, roots, stems, and leaves, and are particularly abundant in edible and medicinal plant species. This review presents a comprehensive overview of recent advances in PDEV research, focusing on their biogenesis, isolation strategies, physicochemical characterization, and cross-kingdom regulatory mechanisms. We highlight the multifaceted roles of PDEVs in anti-tumor immunity, including tumor cell suppression, immune stimulation, drug delivery, and gut-microbiota-mediated immunomodulation. Despite their therapeutic potential, challenges remain in standardization and pharmacokinetic profiling. Emerging engineering strategies offer promising solutions to improve targeting and therapeutic efficacy. Additionally, PDEVs provide a unique platform for mechanistic exploration of traditional Chinese medicine. By integrating current knowledge and future perspectives, this review aims to advance the translational application of PDEVs in cancer immunotherapy and dietary intervention.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017750","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":"Baicalin Induces Ferroptosis in Breast Cancer Through a Novel STAT3/HO-1/GPX4 Regulatory Axis.","authors":"Tingting Guo, Fansu Meng, Detang Li, Maciej Mazur, Alicia Marcelina Díaz García, Mulazim Hussain Asim, Zhong Chen, Yiqi Chen, Yixuan Lin, Zhenjiang Yang, Panpan Wang, Yu Cai","doi":"10.1002/ptr.70426","DOIUrl":"https://doi.org/10.1002/ptr.70426","url":null,"abstract":"<p><p>Breast cancer (BC) is a leading cause of cancer-related mortality worldwide. Ferroptosis is a non-apoptotic regulated cell death that has been linked to the progression of BC and represents a promising therapeutic target for this malignancy. Baicalin (BA) is recognized for its antioxidant, anticancer, and anti-inflammatory effect. Although the ferroptosis-mediated antitumor activity of BA has been widely demonstrated in various cancers, its potential to induce ferroptosis in BC remains unclear. To explore its regulation of ferroptosis in BC and identify the underlying mechanisms, we performed multi-dimensional experiments to investigate the mechanisms of BA-induced ferroptosis. Proliferatively, CCK-8 and colony formation assays were employed to measure the viability and reproductive capacity of cells, complemented by a nude mouse xenograft model for in vivo validation. Subsequently, we demonstrated BA-induced cell death via ferroptosis in vitro and in vivo in BC, accompanied by ROS and lipid peroxidation accumulation, GSH depletion, intracellular liable Fe²⁺ enrichment and mitochondrial damage. Notably, these effects were reversed by ferrostatin-1. The pan-caspase inhibitor Z-VAD-FMK and Fer-1 rescued BA-induced cell death, whereas necroptosis inhibitors necrosulfonamide and necroptosis inhibitor necrostatin-1 as well as autophagy inhibitor chloroquine did not exert such effects. Significantly, ferroptosis serves as the predominant cell death mechanism. Mechanistically, we performed network pharmacology analysis and molecular docking to explore the interaction between BA and STAT3/HO-1/GPX4. Functionally, BA effectively disrupted GPX4-dependent ferroptosis defense and induced BC cell death. As a natural compound modulating this ferroptosis-related axis, BA is a promising therapeutic alternative to conventional chemotherapy, which is limited by severe systemic toxicity. Collectively, this work reveals BA may regulate ferroptosis via the potential STAT3/HO-1/GPX4 signaling axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012757","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":"Gentiopicroside Regulates EGFR and Induces Its Lysosomal Degradation to Attenuate Heart Failure.","authors":"Mingzhen Cao, Da Ke, Jian Ni, Yuan Yuan, Zhang Nan, Xiujun Dai, Heng Zhou","doi":"10.1002/ptr.70452","DOIUrl":"https://doi.org/10.1002/ptr.70452","url":null,"abstract":"<p><p>Cardiac hypertrophy is a major pathological response to cardiovascular stress and a critical contributor to heart failure (HF). Gentiopicroside (GPS), a naturally occurring iridoid glycoside derived from Gentiana scabra, exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties. However, its role and molecular mechanisms in cardiac hypertrophy and HF remain unclear. A pressure overload-induced cardiac remodeling model was established in C57BL/6 mice by transverse aortic constriction (TAC), followed by GPS treatment with or without the EGFR tyrosine kinase inhibitor Canertinib. Cardiac function and remodeling were evaluated by echocardiography, hemodynamic analysis, and histological staining. In vitro, neonatal rat ventricular myocytes (NRVMs) and cardiac fibroblasts (NRCFs) were used to investigate the cellular effects of GPS. EGFR knockdown, conditioned medium transfer, cellular thermal shift assay (CETSA), and lysosomal/proteasomal inhibition experiments were performed to elucidate the mechanism underlying GPS-mediated EGFR regulation. GPS markedly alleviated TAC-induced cardiac hypertrophy and fibrosis in vivo and suppressed Ang II-induced cardiomyocyte hypertrophy. GPS also reduced cardiomyocyte apoptosis and oxidative stress. Mechanistically, GPS acted as an EGFR degrader rather than a conventional kinase inhibitor, reducing total EGFR abundance without inhibiting the kinase activity of remaining receptors, thereby attenuating excessive AKT/ERK1/2 signaling. CETSA and molecular docking indicated direct GPS-EGFR interaction. GPS-induced EGFR reduction was mediated primarily through lysosomal degradation, as demonstrated by chloroquine rescue experiments, whereas proteasome inhibition had limited effects. Co-administration of Canertinib with GPS conferred no additional benefit. EGFR depletion abolished the protective effect of GPS in cardiomyocytes, indicating a cardiomyocyte-autonomous mechanism. This study identifies GPS as a regulator of EGFR stability during pathological cardiac remodeling. By promoting lysosome-dependent EGFR degradation and suppressing excessive AKT/ERK1/2 signaling, GPS attenuates cardiac hypertrophy and remodeling while preserving basal EGFR function, highlighting its potential therapeutic value for HF.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012275","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":"Plant-Derived Natural Product Nanodelivery System in Cancer Therapy.","authors":"Changqi Shi, LuLu Zhang, Lan Yan, Qi Geng, Li Li, Xiaojuan He, Ning Zhao, Yong Tan, Xiaomeng Zhang, Cheng Lu","doi":"10.1002/ptr.70441","DOIUrl":"https://doi.org/10.1002/ptr.70441","url":null,"abstract":"<p><p>Plant-derived natural products have emerged as important sources of anticancer agents because of their diverse chemical structures and broad biological activities. However, their clinical application is often limited by poor aqueous solubility, low membrane permeability, insufficient tumor selectivity, and systemic toxicity. Recent advances in nanodelivery systems have provided effective strategies to overcome these pharmacokinetic and pharmacodynamic barriers by improving drug stability, enhancing tumor-targeted accumulation, and promoting intracellular delivery. In this review, we systematically summarise recent progress in the nanotechnology-based delivery of plant-derived natural products for cancer therapy, with a focus on three major strategies: chemical conjugation, self-assembly of natural products, and codelivery of natural products with chemotherapeutic agents. We further discuss the major advantages of these systems, including improved bioavailability, enhanced targeting capacity, reduced off-target toxicity, and the potential to overcome multidrug resistance. Finally, current challenges in formulation design, safety evaluation, large-scale manufacturing, and clinical translation are highlighted. This review provides a comprehensive framework for the rational development of plant-derived natural product nanomedicines in precision oncology.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012262","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 Polysaccharides for Rheumatoid Arthritis Therapy: Mechanism, Drug Delivery and Clinical Application.","authors":"Luxin Li, Junnan Li, Guangzhi Li, Lili Huang, Tiantian Wen, Yanying Li, Yan Sun, Zhenqiang Liu, Qingshan Chen, Lili Zhang, Tiangang Lu, Ruiyan Wu, Haixue Kuang, Xiaochi Ma, Yan Liu","doi":"10.1002/ptr.70455","DOIUrl":"https://doi.org/10.1002/ptr.70455","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized primarily by chronic synovitis. Clinically, RA manifests as joint pain, swelling, and functional impairment caused by persistent synovial inflammation. Additionally, RA can involve vital organs, including the cardiovascular and respiratory systems, thereby significantly compromising patients' quality of life and increasing the risk of disability. In recent years, natural polysaccharides have attracted increasing attention in research on RA prevention and treatment because of their multi-target regulatory effects, high bioactivity, and low-toxicity. Natural polysaccharides can ameliorate the pathological progression of RA through various mechanisms, including modulating immune balance, suppressing inflammatory responses, alleviating oxidative stress, inhibiting the abnormal proliferation of synovial fibroblasts, and regulating gut microbiota. This review systematically summarizes the pharmacodynamic basis and molecular mechanisms underlying the anti-RA effects of natural polysaccharides reported since 2000, with particular emphasis on recent advances in novel drug delivery technologies and a critical evaluation of clinical application studies. These findings aim to provide scientific evidence and theoretical support for developing new therapeutic strategies involving natural polysaccharides for RA treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991054","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":"Hinokitiol Promotes Neural Repair After Spinal Cord Injury by Reprogramming Microglial Inflammatory and Redox Responses.","authors":"Wenhao Zhang, Jing Wang, Tianyi Wang, Qihao Fu, Jiawen Xu, Chaochen Li, Zheng Zhou, Chenxi Zhang, Guanhua Xu, Mingjie Xia, Zhiming Cui","doi":"10.1002/ptr.70447","DOIUrl":"https://doi.org/10.1002/ptr.70447","url":null,"abstract":"<p><p>Secondary neuroinflammation and oxidative stress, driven partly by maladaptive microglial activation, limit recovery after spinal cord injury (SCI). We investigated whether hinokitiol promotes neural repair and whether nuclear factor erythroid 2-related factor 2 (Nrf2) signaling mediates its effects. Male C57BL/6J mice received T10 contusive SCI and intraperitoneal vehicle or hinokitiol (20 mg/kg once daily for 7 days, starting 6 h after injury). Locomotor, electrophysiological, histological, and single-nucleus transcriptomic outcomes were evaluated. In vitro, lipopolysaccharide-challenged BV2 microglia, BV2-HT22 indirect cocultures, and pharmacological Nrf2 inhibition with ML385 were used to examine inflammatory, oxidative, and neuronal apoptosis outcomes. Hinokitiol improved locomotor and motor-evoked potential outcomes; reduced lesion cavitation, collagen deposition, neuronal loss, demyelination, and astroglial activation; and shifted microglia from inflammatory/oxidative programs toward repair-associated states. Hinokitiol reduced tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and NADPH oxidases 2/4 in spinal cord tissue and BV2 cells. Hinokitiol-pretreated microglia reduced HT22 apoptosis in coculture. Hinokitiol decreased Kelch-like ECH-associated protein 1 and increased Nrf2 and heme oxygenase-1, whereas ML385 attenuated these effects and restored inflammatory and oxidative responses. Hinokitiol supports neural repair after SCI by reprogramming microglial inflammatory-redox states, at least partly through Nrf2 signaling. These findings justify further pharmacokinetic, sex-inclusive, and long-term safety studies.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977529","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":"Chaetocin Induces Ferroptosis in Cisplatin-Resistant Ovarian Cancer Cells Through Neddylation-Mediated TFRC Upregulation.","authors":"Hanfei Xie, Wumin Dai, Lu Sun, Wangang Gong, Tao Zhu, Yingli Zhang","doi":"10.1002/ptr.70446","DOIUrl":"https://doi.org/10.1002/ptr.70446","url":null,"abstract":"<p><p>Ovarian cancer (OV) is a highly lethal gynecological tumor, often developing platinum chemotherapy resistance and treatment failure. With their diverse and complex structures, natural products offer potential solutions to drug resistance. This study systematically examines chaetocin's effects on cisplatin-resistant OV cells and its underlying molecular mechanisms. We utilized a cell counting Kit-8, transwell assays, flow cytometry, immunohistochemistry, and western blotting to evaluate chaetocin's effects on cisplatin-resistant OV cells. Proteomic analysis and bioinformatics were utilized to identify the molecular targets of chaetocin, which were validated via cell transfection and co-immunoprecipitation. Additionally, a cisplatin-resistant OV xenograft model was developed for in vivo studies. Chaetocin suppressed the malignancy of cisplatin-resistant OV cells in a dose-dependent manner to suppress cell proliferation, impede cell migration and invasion, and induce both cell apoptosis and cell cycle arrest. Furthermore, in vivo studies showed that chaetocin inhibited tumor growth in a cisplatin-resistant OV xenograft model. In terms of mechanism, chaetocin induced ferroptosis in these cells, inhibiting TFRC ubiquitination and upregulating its expression by reducing the levels of cullin1 and its neddylation binding (cullin1-NEDD8). Our study uncovers a previously unrecognized mechanism: Chaetocin induces ferroptosis by inhibiting TFRC neddylation to upregulate its expression in OV. Unlike its known role as an SUV39H1 inhibitor, chaetocin functions through the neddylation-TFRC-ferroptosis axis, a pathway not previously linked to this compound. Moreover, while neddylation has recently been reported to regulate ferroptosis via SLC7A11, our study reveals an entirely distinct mechanism involving TFRC-mediated iron transport. This epigenetic regulation stabilizes TFRC, sensitizing resistant cells to ferroptosis, providing a dual-mechanistic insight not found in existing literature. By linking chaetocin's gene regulation to iron-dependent cell death, we offer new insights and potential therapies for cisplatin-resistant OV.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963644","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":"Protective Potentials of Natural Products Against Vascular Dementia: A Comprehensive Review of Experimental Studies.","authors":"Jung-Hoon Kim, Yongtaek Oh, Suin Cho","doi":"10.1002/ptr.70448","DOIUrl":"https://doi.org/10.1002/ptr.70448","url":null,"abstract":"<p><p>Vascular dementia (VaD), accounting for up to 20% of dementia cases globally, is primarily driven by chronic cerebral hypoperfusion (CCH), which leads to progressive cognitive impairment. Despite the increasing prevalence of VaD, effective treatments remain limited. Natural products-including herbal formulas, single herbs, and phytochemicals-have emerged as promising candidates due to their multi-targeted biological activities. This review aimed to evaluate the efficacy and underlying mechanisms of natural products in ameliorating CCH-induced VaD in experimental rodent models, and to identify feasible mechanistic pathways and targets. Protective effects of natural products were mediated by enhanced vascular regeneration, BBB stability, synaptic plasticity, and neurotrophic signaling along with reduced oxidative stress, neuroinflammation, and apoptosis. Among the proteins concerned, the serine/threonine kinase Akt1 emerged as a primary regulatory protein involved in coordinating survival and inflammatory responses. Predominantly male rat models were subjected to bilateral common carotid artery occlusion (BCCAo) or bilateral common carotid artery stenosis (BCAS) to mimic clinical features of CCH. These two models provided a robust and translational strategy for a preclinical approach against VaD. The interconnected network analysis facilitated the discovery of core anti-VaD interventions by linking established herbal formulas with promising, yet understudied, botanical resources. Natural products demonstrate multitargeted protective potential in VaD animal models by targeting multiple pathological processes. Further investigation of underexplored herbs and phytochemicals may expand treatment strategies and support the development of novel and multi-targeted interventions for VaD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963636","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":"Plant-Derived Bioactives and PPAR Signaling in Functional Dyspepsia: Mechanistic Insights and Therapeutic Perspectives.","authors":"Irene Palenca, Emidio Scarpellini, Jan Tack, Pierluigi De Pierro, Giovanni Sarnelli, Giuseppe Esposito","doi":"10.1002/ptr.70449","DOIUrl":"https://doi.org/10.1002/ptr.70449","url":null,"abstract":"<p><p>Functional dyspepsia (FD) is a common disorder of gut-brain interaction in which gastric sensorimotor abnormalities may coexist with impaired duodenal barrier function, low-grade immune activation, and altered neuroimmune signaling. Peroxisome proliferator-activated receptors (PPARs) are relevant to this emerging model because they regulate epithelial differentiation, inflammatory responses, mitochondrial metabolism, redox balance, and lipid-mediator signaling. Impaired duodenal release of palmitoylethanolamide (PEA) provides direct translational evidence that defective PPARα-dependent lipid signaling may contribute to FD. Experimental studies further suggest that several plant-derived bioactives modulate PPAR-related pathways and other mechanisms involved in mucosal adaptation. Whether these effects restore duodenal function or improve clinically meaningful outcomes in humans remains uncertain. This review examines PPAR signaling as a mechanistic link between duodenal dysfunction and the actions of plant-derived bioactives. Therefore, we distinguish disease-specific evidence from findings obtained in other experimental settings and identify priorities for the development of mechanism-based phytotherapy in FD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963647","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}