Phytotherapy Research最新文献

{"title":"Protective Effect of Epigallocatechin-3-Gallate Against Fructose-Induced Metabolic Associated Fatty Liver Disease in Mice by Regulating Ferroptosis and Autophagy via SIRT5.","authors":"Puyu Zhang, Cuiping Hou, Jiayi Liu, Bosheng Wang, Wenqi Liu, Xin Yang, Yubing Kang, Zequn Liu, Yalin Zhang, Zhuxi Liu, Yuhong Zhao, Lu Zhao","doi":"10.1002/ptr.70477","DOIUrl":"https://doi.org/10.1002/ptr.70477","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) lacks effective pharmacological therapies and is strongly associated with excessive fructose consumption. Ferroptosis and autophagy dysregulation are increasingly recognized as key drivers of MAFLD progression. Epigallocatechin-3-gallate (EGCG) exerts hepatoprotective effects. However, whether it regulates SIRT5-mediated ferroptosis and autophagy remains unclear. This study was aimed at investigating whether EGCG ameliorates fructose-induced MAFLD by regulating ferroptosis and autophagy via SIRT5. A fructose-induced MAFLD mouse model and fructose-treated HepG2 cells were established, and EGCG intervention was performed with or without SIRT5 knockdown. Hepatic steatosis, inflammation, ferroptosis- and autophagy-related markers were evaluated by biochemical assays, histological analysis, RT-qPCR, and western blotting analysis. Molecular docking was used to assess the interaction between EGCG and SIRT5. EGCG significantly mitigated hepatic lipid accumulation and inflammation in fructose-induced MAFLD models. It restored SIRT5 expression, alleviated iron overload and oxidative stress, rescued GPX4 and FTH1 expression, and downregulated FTL and COX2 levels. EGCG also improved autophagy, as reflected by an elevated LC3-II/LC3-I ratio and LAMP2 expression, together with reduced SQSTM1/p62 accumulation. Importantly, SIRT5 knockdown abolished these protective effects, suggesting a SIRT5-dependent mechanism. Molecular docking analysis further verified a robust binding affinity between EGCG and SIRT5. Collectively, our results demonstrate that EGCG ameliorates fructose-induced MAFLD by modulating ferroptosis and autophagy through SIRT5 upregulation, highlighting SIRT5 as a potential therapeutic target and supporting EGCG as a promising intervention for MAFLD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128304","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":"Benefits and Harms of Herbal Medicines for Preventing and Treating Acute Respiratory Infections: An Overview of Systematic Reviews.","authors":"Fariba Aghajafari, Brian Choi, Devansh Bhatt, Susanna Maltoni, Elizabeth T Thomas, Elena C Rosca, Sara Gandini, Annette Plüddemann, Carl J Heneghan, John M Conly, Tom Jefferson, Igho J Onakpoya","doi":"10.1002/ptr.70464","DOIUrl":"https://doi.org/10.1002/ptr.70464","url":null,"abstract":"<p><p>Hundreds of herbal medicines are currently marketed for the management of acute respiratory infections (ARIs). However, there is uncertainty about their benefits and harms, and clinical guidance remains unclear. Our objective was to evaluate the benefits and harms of herbal medicines for preventing and treating ARIs using the evidence from published systematic reviews. We conducted electronic searches in MEDLINE, Embase, CINAHL, and the Cochrane Library. We also searched Google Scholar and the bibliography of relevant studies. We included reviews of herbal medicines or herbal medicine combinations for the prevention or treatment of ARIs. Our primary outcomes were infection rates, symptom resolution, symptom duration, and symptom severity. We used AMSTAR-2 criteria to assess the quality of included reviews. Two reviewers independently screened abstracts, assessed quality, and extracted the data. We included 18 reviews evaluating the effectiveness of 16 different herbal medicines. A total of 13 were rated high quality, and five were rated moderate quality. Seven reviews of ginseng, ivy leaf extract, echinacea, eucalyptus, and black elderberry showed some benefits in the management of ARIs. The evidence from the remaining 11 reviews was either insufficient or inconclusive. No serious adverse events were reported; however, adverse events were likely underreported. Herbal medicines show modest benefits for managing ARIs, but the evidence remains limited by methodological flaws in the primary studies. While some treatments appear promising, current data are insufficient for strong clinical recommendations. High-quality, large-scale RCTs are needed to confirm efficacy, assess safety, and guide clinical use.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113593","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":"Multi-Target Pharmacological Mechanisms of Salvia miltiorrhiza Bunge in Metabolic Syndrome and Cardiovascular Diseases: A Comprehensive Review Based on the Theory of \"Same Treatment for Different Diseases\".","authors":"Zhiyi Jia, Kaiyi Wu, Jiaying Qi, Nana Huang, Yusheng Liu, Xiumei Gao, Rong Sun","doi":"10.1002/ptr.70442","DOIUrl":"https://doi.org/10.1002/ptr.70442","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) represents a clinical disorder characterized by the clustering of conditions including obesity, elevated blood sugar levels, and high lipid levels, which are intricately linked to the onset of cardiovascular diseases (CVDs), such as atherosclerosis, myocardial ischemia-reperfusion injury (MIRI), and heart failure (HF). Salvia miltiorrhiza Bunge (SM), recognized as a blood-regulating herb in traditional Chinese medicine (TCM), is renowned for its effects in activating blood and resolving stasis. By summarizing the pharmacological research progress and clinical efficacy of SM and its active components in the management of MetS and CVDs, this review analyzes its multi-dimensional pharmacological characteristics and multi-target action pathways, and identifies common pharmacological effects and target networks. Through a comprehensive computational integration of network pharmacology, bioinformatics analyses, ADMET profiling, PASS online bioactivity prediction, and molecular docking, candidate targets and shared signaling pathways underlying the therapeutic potential of SM in MetS and CVDs were explored. These findings were then interpreted in the context of an integrated appraisal of clinical evidence for various SM preparations in managing MetS and CVDs, together with a thorough examination of pharmacological data on SM and its major bioactive compounds. The reviewed clinical and experimental evidence indicates that SM-containing formulations and major SM constituents may modulate several pathophysiological mechanisms shared by MetS and CVDs, particularly inflammation, metabolic dysregulation, oxidative stress, and tissue remodeling. The exploratory computational integration further prioritized PIK3CG, IKBKB, JAK2, STAT3, and IL1B as candidate shared targets associated with NF-κB, PI3K/Akt, MAPK, and AGE/RAGE signaling. SM and its active components have shown potential multi-target, multi-pathway, and multi-action effects in MetS and CVDs, providing preliminary evidence for the treatment principle of \"same treatment for different diseases.\"</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113565","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":"Tangeretin Targets Macrophage M1 Polarization to Alleviate Liver Injury in a Murine Model of Hepatic Sinusoidal Obstruction Syndrome.","authors":"Fumin Zhang, Cheng Zhu, Xingyu Li, Tianyin Sun, Yongkang Zhang, Mengwei Wu, Qianqian Zhang, Ying Dai, Xuecan Mei, Derun Kong","doi":"10.1002/ptr.70475","DOIUrl":"https://doi.org/10.1002/ptr.70475","url":null,"abstract":"<p><p>Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening liver microvascular disorder characterized by hepatic sinusoidal endothelial cells (HSECs) injury, for which safe and effective pharmacological treatments are currently lacking. Tangeretin (TAN), a natural polymethoxylated flavone, exhibits anti-inflammatory, antioxidant, and hepatoprotective properties. However, its therapeutic potential and mechanisms in HSOS remain unclear. This study investigated the protective role and molecular mechanisms of TAN against monocrotaline (MCT)-induced HSOS. In the murine HSOS model, TAN intervention alleviated hepatic sinusoidal congestion, lobular injury and elevated serum transaminase levels in a dose-dependent manner. Mechanistic studies revealed that TAN blocks the binding of Keap1 and Nrf2, inhibits Keap1-mediated ubiquitination and degradation of Nrf2, and facilitates its nuclear translocation. Activated Nrf2 enhances mitophagy and restores mitochondrial homeostasis, thereby suppressing NLRP3 inflammasome activation and M1 macrophage polarization to alleviate hepatic sinusoidal endothelial cell injury. Furthermore, genetic ablation of NLRP3, or pharmacological blockade of Nrf2 (ML385) and mitophagy (Mdivi-1), markedly attenuated the protective effects of TAN in restraining M1 macrophage polarization and ameliorating HSOS pathological lesions. In conclusion, TAN activates the Keap1-Nrf2 pathway and promotes mitophagy, which further inhibits NLRP3 inflammasome activation and M1 macrophage polarization, ultimately alleviating MCT-induced hepatic sinusoidal obstruction syndrome. These findings suggest that TAN may serve as a potential candidate drug for the treatment of HSOS.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113613","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":"Curcumin Delivery Systems for Inflammatory Skin Application: A Review.","authors":"Xueer Zhang, Pai Zheng, Yuesi Qin, E Liu, Yanjiao Xiong, Siyan Chen, Jing Guo","doi":"10.1002/ptr.70275","DOIUrl":"https://doi.org/10.1002/ptr.70275","url":null,"abstract":"<p><p>Curcumin (CUR) is a low-molecular-weight polyphenolic compound extracted from the rhizomes of the herb Curcuma longa. It exhibits a wide range of pharmacological activities, including anti-inflammatory, antioxidant, hypoglycemic, and antiviral effects. However, its poor solubility, low stability, and rapid metabolism significantly hinder its clinical application. In recent years, encapsulating drugs within natural polymer-based nanoparticle systems has significantly enhanced their penetration into deeper skin layers. Nanocarriers such as CUR-loaded nanoliposomes, polymeric nanoparticles, and polymeric micelles have notably improved its pharmacological activity and prolonged its retention time. This review summarizes the applications of CUR delivery systems in the treatment of inflammatory skin diseases and discusses the potential anti-inflammatory biological mechanisms underlying their therapeutic effects.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113576","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":"Broussonin A Attenuates Type 2 Diabetic Osteoporosis by Reactivating JAK2/STAT3 Signaling to Inhibit Ferroptosis in BMSCs.","authors":"Yangfan Guo, Yixun Huang, Lijiang Han, Yikai Wang, Wenjie Ruan, Haijun Liu, Yitian Bu, Shenghuan Wu, Xinyi Zhou, Yuxuan Zhou, Jian Luo, Weikai Chen, Chen Jin, Lei Yang","doi":"10.1002/ptr.70417","DOIUrl":"10.1002/ptr.70417","url":null,"abstract":"<p><p>Type 2 diabetic osteoporosis (T2DOP) significantly impairs bone health, partially through ferroptosis triggered by glucolipotoxicity. However, therapeutic strategies targeting this process remain largely unexplored. Broussonin A (BRA), a natural antioxidant compound, shows potential for treating bone metabolic disorders, yet its specific effects on T2DOP are unclear. This study aimed to examine whether BRA inhibits ferroptosis and restores bone quality under type 2 diabetic conditions. A rat model of T2DOP was established by administering streptozotocin (STZ) combined with a high-fat dietary regimen. Additionally, an in vitro model was developed through the exposure of bone marrow mesenchymal stem cells (BMSCs) to high-glucose/high-lipid (HGHF) conditions. Intracellular Fe²⁺ and lipid peroxidation levels were determined using FerroOrange and C11-BODIPY staining techniques separately. Mitochondrial integrity and function were assessed via JC-1 staining and ultrastructural examination. Furthermore, assays for osteogenic differentiation, Western blotting (WB), and immunofluorescence (IF) analyses were performed. The results showed that BRA markedly reduced cytotoxicity induced by high-glucose/high-lipid exposure, decreased lipid peroxidation and Fe²⁺ overload, restored mitochondrial integrity and antioxidant enzyme activities, and rescued impaired osteogenic function in BMSCs. In vivo administration of BRA maintained femoral trabecular microarchitecture without observable toxicity to major organs. Network pharmacology analysis and cellular thermal shift assays identified the JAK2/STAT3 signaling pathway as the direct molecular target. Treatment with BRA effectively restored the phosphorylation states of JAK2 and STAT3, leading to an elevation in GPX4 protein expression. Importantly, knockdown of STAT3 through siRNA interference abolished these protective effects. Taken together, these findings indicate that BRA mitigates T2DOP by reactivating the JAK2/STAT3 signaling axis, thereby suppressing ferroptosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5720-5740"},"PeriodicalIF":8.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382524","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":"Curcumin as a Multifaceted Epigenetic Modulator With a Disease-Oriented Perspective.","authors":"Hedieh Sadat Shamsnia, Mahtab Roustaei, Amirreza Peyrovinasab, Mazyar Ataei, Fatemeh Shafiean, Mohammadmahdi Ghavamipour Komleh, Mobina Tajdari, Mohammad Mahdi Khosravi Nia, Sayna Sadeghi Kivi, Amir Hossein Abdolghaffari","doi":"10.1002/ptr.70401","DOIUrl":"10.1002/ptr.70401","url":null,"abstract":"<p><p>Curcumin (diferuloylmethane), a polyphenolic compound, is a component of Curcuma longa , commonly known as turmeric. It is well known for its therapeutic properties in a variety of diseases. One of its distinctive mechanisms is epigenetic modification. Epigenetic changes involve alterations in DNA methylation, histone modifications, and non-coding RNA expression patterns, which are interconnected and play a crucial role in various pathologies. It has been shown that curcumin inhibits DNA methyltransferases (DNMT), thereby reversing abnormal hypermethylation and reactivating silenced genes. Concurrently, it downregulates histone deacetylases (HDACs), promotes histone acetyltransferase (HAT) activity, and modulates the expression of non-coding RNAs, including miRNAs. Consequently, curcumin regulates many mechanisms, including inflammatory cascades, oxidative stress responses, and neuronal function. Curcumin's broad-spectrum activity has been demonstrated in various pathologies. For instance, in cancer, it modulates epigenetic mechanisms to support tumor suppression; in neurodegenerative diseases, it enhances neuronal survival; and in metabolic disorders, it improves insulin responsiveness. It also reduces inflammation and fibrosis in cardiovascular, hepatic, renal, and inflammatory conditions. This review will describe curcumin's diverse role as an epigenetic modulator from a novel disease-oriented perspective.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5639-5671"},"PeriodicalIF":8.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376352","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":"Interventional Potential of Panax Genus Chinese Medicinals in Atherosclerosis Progression.","authors":"Wenjing Li, Haiyan Li, Ronghua Zhao, Liangliang Fan, Lijia Yin, Fusong Dong, Xuxia Jia, Song Yang, Xueyuan Bai, Daqing Zhao, Jiawen Wang","doi":"10.1002/ptr.70412","DOIUrl":"10.1002/ptr.70412","url":null,"abstract":"<p><p>Atherosclerosis and its complications significantly affect human health globally. The etiology of atherosclerosis is multifaceted, with current research focusing on abnormalities in lipid metabolism, immune cell activation, inflammation, and epithelial damage. Currently, highly effective preventive and therapeutic strategies for atherosclerosis remain lacking. Recent reports have indicated the anti-atherosclerotic effects of medicinal herbs from the Araliaceae family, including Panax ginseng C. A. Mey., Panax notoginseng , Panax quinquefolius L., and Panax japonicus . The pharmacological effects of these herbs on atherosclerosis include lipid metabolism, immune cell activation, inflammation, oxidative stress, endothelial function, cell proliferation and migration, angiogenesis, apoptosis, autophagy, and gut microbiota homeostasis. This review aims to comprehensively elucidate, summarize, and update the protective effects and underlying mechanisms of Araliaceae herbs against atherosclerosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5787-5804"},"PeriodicalIF":8.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423262","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 Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.","authors":"Md Rezaul Islam, Abdur Rauf, F M Shourav, Hanan A Ogaly, Abdullah S M Aljohani, Waleed Al Abdulmonem, Kamala Badalova, Marcello Iriti","doi":"10.1002/ptr.70430","DOIUrl":"10.1002/ptr.70430","url":null,"abstract":"<p><p>Pancreatic cancer, especially pancreatic ductal adenocarcinoma, is known for its aggressive nature, late diagnosis, and resistance to standard treatments. This review demonstrates the therapeutic potential of phytochemicals as multitarget agents in pancreatic cancer, emphasizing their molecular mechanisms, pharmacological properties, and translational relevance. Important carcinogenic signaling pathways, such as KRAS/MAPK, PI3K/Akt, NF-κB, STAT3, Hedgehog, and Wnt/β-catenin, are modulated by phytochemicals like curcumin, quercetin, resveratrol, and others. These substances demonstrate anticancer effects by suppressing epithelial-mesenchymal transition, inducing apoptosis, reducing proliferation and angiogenesis, and modulating oxidative stress. Preclinical research indicates consistent multipathway targeting and potential enhanced efficacy with traditional chemotherapeutics, although evidence from clinical studies remains limited and inconsistent. New strategies to improve drug stability, target tumors more effectively, and enhance treatment outcomes involve the use of combination medicines and nanotechnology-based delivery systems. The gap between preclinical effectiveness and clinical translation continues due to insufficient large-scale trials, diverse study designs, and a lack of standardized dosing strategies. Phytochemicals show potential as multitarget treatments for pancreatic cancer, but their clinical application is inhibited by pharmacokinetic challenges and insufficient validation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5973-5987"},"PeriodicalIF":8.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766351","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":"Piper nigrum Has an Antitumor Effect Through Regulation of the Phosphatidylinositol 3-Kinase Signaling Pathway in a Murine Model of Acute Myeloid Leukemia.","authors":"Natalia Murillo, Paola Lasso, Claudia Urueña, Susana Fiorentino","doi":"10.1002/ptr.70423","DOIUrl":"10.1002/ptr.70423","url":null,"abstract":"<p><p>The search for safer and more effective therapies for acute myeloid leukemia (AML) has intensified due to low response rates and resistance to current chemotherapy. The aim of this study was to evaluate the antitumor and immunomodulatory effects of Piper nigrum extract in a murine model of AML, with particular emphasis on its ability to modulate the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway. The chemical composition of the extract was characterized using advanced analytical techniques. In vitro assays were performed to evaluate cytotoxic and cytostatic effects, glucose consumption and ROS production, modulation of Gal-9 (galectin 9) and PD-L1 (programmed death-ligand 1), focusing on and relating it to the modulation of the (PI3K/AKT/mTOR) pathway. In vivo studies were performed using mice inoculated with DA-3/ER-GM cells to evaluate hematological parameters, survival, and immune response after P. nigrum treatment. P. nigrum extract demonstrated cytotoxic and cytostatic activity in vitro, characterized by a decrease in cell proliferation and survival possibly associated with modulation of the PI3K/AKT/mTOR pathway. In the murine AML model, treatment significantly reduced circulating blasts, improved hematological parameters, and prolonged survival. In addition, an increase in effector memory CD8⁺ T cells was observed, along with a reduction in plasma proinflammatory cytokine levels. Piper nigrum may represent a promising complementary therapeutic strategy for AML, acting as an antitumor and immunometabolic modulator. These findings suggest potential clinical applications of P. nigrum extract as an adjuvant or alternative therapy in the treatment of AML, warranting further preclinical and clinical investigation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5988-6004"},"PeriodicalIF":8.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796617","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}