Phytomedicine最新文献

{"title":"AANG: A natural compound formulation for targeting macrophage-myofibroblast transition in non-small-cell lung carcinoma","authors":"Max Kam-Kwan Chan ,&nbsp;Philip Chiu-Tsun Tang ,&nbsp;Zoey Zeyuan Ji ,&nbsp;Jeff Yat-Fai Chung ,&nbsp;Aaron Qi Zhang ,&nbsp;Yan-Fang Xian ,&nbsp;Qing Zhang ,&nbsp;Chun-Kwok Wong ,&nbsp;Ka-Fai To ,&nbsp;Chunjie Li ,&nbsp;Dongmei Zhang ,&nbsp;Patrick Ming-Kuen Tang","doi":"10.1016/j.phymed.2026.157921","DOIUrl":"10.1016/j.phymed.2026.157921","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). They are highly heterogeneous containing both anti-cancer and pro-tumor populations, which largely limits their translational development. Recently, we have identified macrophage‐myofibroblast transition (MMT) as a novel and key origin of pro-tumoral CAF in non-small-cell lung cancer (NSCLC), targeting it with Traditional Chinese Medicine (TCM) may represent a safe and effective strategy for solid tumors. Here, by spatial single-cell bioinformatics, we revealed that not only Smad3 activation but also Smad7 reduction occurs in the macrophages undergoing MMT in clinical NSCLC. Therefore, we optimized our well-established TCM-derived natural product formulation AANG, which remodulated TGF-β1/Smad3/Smad7 signaling and synergistically blocked MMT on the bone marrow derived macrophages (BMDM) in vitro. More encouragingly, this optimized AANG can effectively block MMT-derived cancer progression on mouse cancer models with syngeneic lung cancer LLC and human NSCLC xenograft A549 without side-effect in vivo. Thus, AANG may represent the first natural compound formulation for blocking MMT-derived pro-tumoral CAF formation in the clinical NSCLC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157921"},"PeriodicalIF":8.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geum japonicum Thunb. var. Chinese-P.decorata H.Andres herbal pair ameliorates CIRI-induced neuronal injury by facilitating mitochondrial transfer via the CD38/Miro1 signaling pathway","authors":"Feiyue Sun ,&nbsp;Ruining She ,&nbsp;Tong Yang ,&nbsp;Bei Chen ,&nbsp;Zi Liao ,&nbsp;Jun Liao ,&nbsp;Zhigang Mei","doi":"10.1016/j.phymed.2026.157928","DOIUrl":"10.1016/j.phymed.2026.157928","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia-reperfusion injury (CIRI) leads to severe mitochondrial dysfunction, which is a critical trigger of widespread neuronal apoptosis. Therefore, restoring mitochondrial homeostasis represents a key strategy for neuroprotection. Clinical observations suggest that the herbal pair <em>Geum japonicum</em> Thunb. var. <em>chinense</em>-<em>P. decorata</em> H. Andres (GJ-PD) shows therapeutic advantages in alleviating CIRI. However, its precise neuroprotective effects and underlying molecular mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the protective mechanisms of combined GJ-PD against CIRI, with particular emphasis on mitochondrial transfer and neuronal PANoptosis.</div></div><div><h3>Methods</h3><div>Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify the chemical constituents of GJ-PD in brain. The mechanisms of GJ-PD in CIRI were investigated using transmission electron microscopy, Western blotting, immunofluorescence, immunohistochemistry, and pathological staining. In addition, an <em>in vitro</em> oxygen-glucose deprivation/reoxygenation (OGD/R)-induced co-culture injury model was established using HT22 neurons and C8-D1A astrocytes. Scanning electron microscopy and laser confocal microscopy combined with MitoTracker staining were applied to explore the effects of GJ-PD on mitochondrial transfer and neuronal PANoptosis. Furthermore, the involvement of CD38 and Miro1 was examined using CD38- and Miro1-overexpression plasmids, both alone and in combination with GJ-PD treatment.</div></div><div><h3>Results</h3><div>GJ-PD exhibited significant neuroprotective effects following CIRI. It reduced cerebral infarct volume, alleviated neuronal oxidative stress and mitochondrial dysfunction, and increased CD38 and Miro1 expression, thereby attenuating programmed cell death. These effects contributed to its anti-CIRI efficacy. <em>In vitro</em> results were consistent with <em>in vivo</em> findings. Treatment with GJ-PD-containing plasma alone in the co-culture system enhanced mitochondrial transfer from C8-D1A astrocytes to neurons via tunneling nanotubes (TNTs). This was accompanied by increased neuronal proliferation and ATP production, along with reduced neuronal PANoptosis. Co-treatment with CD38- or Miro1-overexpressing C8-D1A cells further improved cell viability and ATP levels, decreased the expression of programmed cell death-related proteins, and elevated CD38 and Miro1 protein expression. Notably, Miro1 overexpression did not significantly affect CD38 expression.</div></div><div><h3>Conclusions</h3><div>GJ-PD promotes the transfer of astrocytic mitochondria to neurons via TNTs through the CD38/Miro1 pathway. This process alleviates neuronal PANoptosis and improves neurological function, thereby exerting protective effects against CIRI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157928"},"PeriodicalIF":8.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloesin improves metabolic associated fatty liver disease and obesity by targeting TGFBR1","authors":"Jianfeng Wu ,&nbsp;Siqi Liu ,&nbsp;Zhen Ma ,&nbsp;Badrakh Munkhbayar ,&nbsp;Qichao Liao ,&nbsp;Menglong Hou ,&nbsp;Yutian Wei ,&nbsp;Yang Xiao ,&nbsp;Yang Wang ,&nbsp;Ruxue Chen ,&nbsp;Batbold Batsaikhan ,&nbsp;Khongorzul Batchuluun ,&nbsp;Lei Zhou ,&nbsp;Yixing Li","doi":"10.1016/j.phymed.2026.157922","DOIUrl":"10.1016/j.phymed.2026.157922","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic associated fatty liver disease (MAFLD) is a chronic liver condition with a high global prevalence. Obesity and its associated insulin resistance are among the main risk factors for MAFLD, for which no effective clinical treatments are currently available. Aloesin, a natural chromone compound derived from <em>Aloe vera,</em> has anti-inflammatory, antioxidant, anticancer, and antidiabetes activity. However, its involvement in MAFLD has not been systematically studied.</div></div><div><h3>Purpose</h3><div>This study investigated the effectiveness of aloesin against MAFLD and obesity and elucidated its potential molecular mechanism.</div></div><div><h3>Methods</h3><div>Aloesin was added to the high-fat diet-of an induced mouse model and to oleic acid/palmitic acid-induced HepG2 cells to explore its effect on lipid metabolism. Molecular targets were identified by reverse docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS).</div></div><div><h3>Results</h3><div>Aloesin significantly reduced lipid accumulation in hepatocytes in both the high-fat diet-induced MAFLD mouse model and the oleic acid/palmitic acid-induced HepG2 cells. It also alleviated oxidative stress and energy metabolism disorders and decreased the body fat mass in mice fed the high-fat diet, which ameliorated the pathological features of MAFLD and obesity. Target prediction and validation identified TGFBR1 as a direct target of aloesin, which was confirmed by CETSA and DARTS. Functional experiments demonstrated that overexpression of TGFBR1 increased lipid accumulation and metabolic disturbances, which were reversed by aloesin.</div></div><div><h3>Conclusion</h3><div>Aloesin improved lipid deposition and slowed the progression of MAFLD by targeting TGFBR1. The results support its potential application for the prevention and treatment of MAFLD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157922"},"PeriodicalIF":8.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Effusol ameliorates ischemic stroke by targeting NLRP3 protein to regulate NLRP3 inflammasome-mediated pyroptosis” [Phytomedicine, 136 (2025) 156253/PMID: 39615210]","authors":"Libin Xu ,&nbsp;Siyu Li ,&nbsp;Jiaxin Qi ,&nbsp;Yan Mi ,&nbsp;Ying Zhang ,&nbsp;Yuxin Yang ,&nbsp;Yingjie Wang ,&nbsp;Di Zhou ,&nbsp;Ning Li ,&nbsp;Yue Hou","doi":"10.1016/j.phymed.2026.157834","DOIUrl":"10.1016/j.phymed.2026.157834","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157834"},"PeriodicalIF":8.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of crocetin, a constituent of saffron, on indomethacin-induced gastric ulcer and related anxiety-like behavior in rats","authors":"Sina Tamaddonfard ,&nbsp;Amir Abbas Farshid ,&nbsp;Esmaeal Tamaddonfard ,&nbsp;Seyedeh Soraya Mahmoudi ,&nbsp;Amir Erfanparast ,&nbsp;Mehdi Imani","doi":"10.1016/j.phymed.2026.157918","DOIUrl":"10.1016/j.phymed.2026.157918","url":null,"abstract":"<div><h3>Background</h3><div>Crocetin (CRT), one of the active ingredients in saffron, exerts health-promoting effects on body systems such as neuroprotective, cardioprotective and hepatoprotective properties.</div></div><div><h3>Purpose</h3><div>In the present study, the effects of CRT and lansoprazole (LAP), as a reference drug, were investigated on indomethacin (IND)-induced gastric ulcer and related anxiety.</div></div><div><h3>Methods</h3><div>Thirty rats were divided into five groups of six. Groups 1 and 2 received vehicle and groups 3, 4 and 5 received CRT (5 and 20 mg/kg) and LAP (30 mg/kg) for seven consecutive days. All groups were deprived of food on day 6. On day 7, group 1 was treated with vehicle and groups 2, 3, 4 and 5 received 50 mg/kg IND. Anxiety and locomotor activity were recorded, and then the animals were euthanized and stomach and hippocampus samples were taken. The effects of the aforementioned treatments were studied in 24 intact rats in four equal groups.</div></div><div><h3>Results</h3><div>CRT (20 mg/kg) and LAP restored IND-induced alterations in the gastric content volume and pH and ulcer index and protection and cyclooxygenases 1 and 2 and prostaglandin E2 and gastric mucosal and hippocampal superoxide dismutase, malondialdehyde, tumor necrosis factor-alpha, interleukin-1β and caspase-3 and hippocampal brain derived neurotrophic factor. Histopathological alterations in the gastric mucosa and hippocampus were improved, and anxiety was suppressed. Intact rats were not influenced.</div></div><div><h3>Conclusions</h3><div>CRT and LAP caused protective effects against IND-induced gastric ulcer and by antioxidative, anti-inflammatory, anti-apoptotic and PGE₂-increasing activities. Anxiolytic effects of CRT and LAP were also observed.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157918"},"PeriodicalIF":8.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renqingchangjue ameliorates MNNG-induced chronic atrophic gastritis by inhibiting the TNF/NF-κB/Caspase-3 axis","authors":"Yuan Chen ,&nbsp;Guang Yue ,&nbsp;Yanjun Liu ,&nbsp;Wei Wang ,&nbsp;Ge Jiang ,&nbsp;Jinhua Zhang ,&nbsp;Zhuo Ga ,&nbsp;Yanfei Zhang ,&nbsp;Xiaoya Liu ,&nbsp;Qingjia Ren ,&nbsp;Caolong Li","doi":"10.1016/j.phymed.2026.157920","DOIUrl":"10.1016/j.phymed.2026.157920","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic atrophic gastritis (CAG) is a pivotal premalignant stage in the Correa cascade, characterized by progressive and largely irreversible loss of gastric glands and an elevated risk of gastric cancer. Renqingchangjue (RQCJ), a classical Tibetan multi-herb formula, has demonstrated clinical and pharmacological benefits in gastritis, yet its mechanisms of action in CAG remain inadequately defined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to clarify the therapeutic efficacy and mechanistic basis of RQCJ in CAG.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We established a network pharmacology–bioinformatics workflow to predict potential RQCJ targets in CAG, integrating targets obtained from TCMSP/SwissTargetPrediction with CAG-related genes to construct a STRING protein–protein interaction (PPI) network and perform GO/KEGG enrichment analyses. Constituents were characterized by UHPLC–HRMS/MS. An MNNG-induced CAG mouse model (control group, model group, Weifuchun positive control group, RQCJ low-dose group and RQCJ high-dose group) was validated by histopathology (H&amp;E), immunohistochemistry (IHC), immunofluorescence (IF), TUNEL, ELISA, and Western blot (WB). In vitro, MNNG-injured GES-1 cells were evaluated using CCK-8, scratch wound-healing, and Annexin V–FITC/PI flow cytometry. Mechanistically, RT-qPCR, WB, and reference-based transcriptome sequencing of gastric tissue were employed, and compound druggability was assessed by AutoDock Vina docking.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;RQCJ markedly ameliorated MNNG-induced chronic atrophic gastritis in vivo and in vitro. UHPLC–HRMS/MS profiling identified 43 constituents, of which 31 were detected as circulating prototypes. Network pharmacology first predicted 154 putative RQCJ–CAG targets enriched in TNF/NF-κB signaling; integrating serum-absorbed component targets with CAG-related genes refined this to 140 high-confidence targets with consistent TNF/NF-κB enrichment. Functionally, RQCJ (20–40 μg/mL) improved GES-1 cell viability and migration while suppressing apoptosis, and in mice dose-dependently repaired gastric mucosal architecture, lowered TNF-α, IL-1β and IL-6, and normalized gastrin and pepsinogen. RQCJ also reduced IL-8, CCL2 and CXCL1 mRNA and increased IL-10 in both models. Mechanistically, it inhibited phosphorylation of IKKβ, IκBα and NF-κB p65 in a dose- and time-dependent manner, decreased cleaved caspase-8/3, restored the Bax/Bcl-2 ratio. Transcriptomics confirmed enrichment of NF-κB and apoptosis pathways, and intersecting differentially expressed genes with the 140 serum-based targets yielded 99 core genes converging on TNF/NF-κB-mediated apoptosis. Molecular docking further supported target engagement, with a chromen-7-ol derivative showing strong predicted affinity for MMP9.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Together, these multi-level data indicate that RQCJ exerts clinically relevant protection against CAG via multi-component su","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157920"},"PeriodicalIF":8.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer’s disease: Metabolite signaling, neuroimmune circuits, and systems-level regulation","authors":"Dong Xue ,&nbsp;Xixi Hu ,&nbsp;Ranchang Li ,&nbsp;Tongyu Sun ,&nbsp;Siying Qian ,&nbsp;Fuxin Chu ,&nbsp;Huawu Gao ,&nbsp;Feng Li ,&nbsp;Biao Cai","doi":"10.1016/j.phymed.2026.157919","DOIUrl":"10.1016/j.phymed.2026.157919","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is increasingly recognized as a multisystem disorder shaped not only by central neurodegeneration but also by peripheral metabolic and immune dysregulation. Growing evidence highlights the gut microbiota and its metabolites as key modulators of amyloid accumulation, tau phosphorylation, neuroinflammation, and microglial dysfunction.</div></div><div><h3>Purpose</h3><div>This review aims to synthesize current advances on how plant-derived bioactive compounds modulate AD pathophysiology through microbiota-dependent metabolic and neuroimmune mechanisms, and to establish a systems-level framework linking botanical interventions to gut microbiota remodeling and metabolite signaling.</div></div><div><h3>Methods</h3><div>A comprehensive literature survey was conducted using PubMed, Web of Science, ScienceDirect, and Google Scholar, covering publications from 2010 to 2026. Studies investigating gut microbiota, microbial metabolites, and plant-derived bioactive compounds in AD-related metabolic, immune, and neurodegenerative pathways were systematically reviewed and integrated.</div></div><div><h3>Results</h3><div>Plant-derived bioactive compounds, including phytochemicals, polysaccharides, and multi-herb formulations, interact extensively with the gut microbiota, undergoing microbial biotransformation to yield more active metabolites while simultaneously reshaping microbial community structure and metabolite profiles. These bidirectional interactions position the microbiota as a central mediator of plant-derived therapeutic activity. We summarize current evidence on how plant-derived compounds influence AD pathophysiology through microbiota-dependent metabolic and neuroimmune pathways. Major microbial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids (BAs), and indole derivatives, are discussed, together with their regulatory roles in signaling networks such as nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/Akt (PI3K/Akt), cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF), and triggering receptor expressed on myeloid cells 2 (TREM2)-associated microglial states. We further summarize evidence for synergistic strategies combining plant bioactives with probiotics and highlight advances in microbial biotransformation, precision metabolite modulation, and engineered microbial systems. Finally, future directions integrating multi-omics, personalized microbiota-guided interventions, and synthetic biology are outlined to support the development of targeted, mechanism-based therapies.</div></div><div><h3>Conclusion</h3><div>By framing AD through a gut microbiota-centered perspective, this review provides a unified mechanistic foundation for the development of next-generation interventions based on plant-derived compounds and microbiota regulation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157919"},"PeriodicalIF":8.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bupleurum chinense ameliorates metabolic-associated fatty liver disease by modulating Sirtuin 6","authors":"Siqi Liu ,&nbsp;Penglong Chen ,&nbsp;Yayi Li ,&nbsp;Zhisen Pan ,&nbsp;Can Zhang ,&nbsp;Anquan Li ,&nbsp;Chongyan Huang ,&nbsp;Hongxuan Zheng ,&nbsp;Like Chen ,&nbsp;Chuangpeng Shen","doi":"10.1016/j.phymed.2026.157905","DOIUrl":"10.1016/j.phymed.2026.157905","url":null,"abstract":"<div><h3>Background</h3><div><em>Bupleurum chinense</em> (Bc) is a traditional Chinese medicine commonly used to treat metabolic-associated fatty liver disease (MAFLD), demonstrating hepatoprotective, anti-inflammatory, and antioxidant effects. Sirtuin 6 (SIRT6) regulates fatty acid metabolism and oxidative stress, playing a crucial role in MAFLD treatment.</div></div><div><h3>Purpose</h3><div>To investigate Bc’s mechanisms in ameliorating MAFLD and analyze the primary active components contributing to its therapeutic effects.</div></div><div><h3>Methods</h3><div>C57BL/6J mice developed MAFLD through 12-week high-fat diet (HFD) feeding, followed by 4-week interventions with Bc decoction (1.3, 0.65, 0.325 g/kg/d) or pioglitazone (0.1 g/kg/d). Lipid metabolism, oxidative stress, inflammation, and insulin resistance were measured. RNA-seq identified the key Bc targets, which were validated in liver-specific knockout mice. Bioactive constituents were initially screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, followed by molecular docking, dynamics simulations, and microscale thermophoresis (MST) to validate target affinity and binding stability. An in vitro MAFLD model was established using primary mouse hepatocytes (MPHs) challenged with oleic and palmitic acid (OAPA).</div></div><div><h3>Results</h3><div>Bc significantly ameliorated lipid accumulation and HFD-induced oxidative stress. Pioglitazone and Bc (1.3 g/kg/d) administration demonstrated marked reductions in circulating TG, ALT, and AST concentrations in a dose-responsive manner. Furthermore, Bc ameliorated hepatic oxidative stress, as evidenced by elevated GSH and SOD levels alongside reduced H₂O₂ content. Transcriptomic profiling and mechanistic validation identified SIRT6 as the central mediator. Bc upregulated SIRT6 expression and enhanced its deacetylase activity, resulting in reduced acetylation of histone H3K9 and H3K56 compared to HFD controls. This promoted PPARα/NRF2 nuclear translocation, upregulating fatty acid β-oxidation genes (such as <em>Cpt1a</em>) and antioxidant genes (such as <em>Ho-1</em>). Crucially, hepatocyte-specific Sirt6 knockout abolished Bc's therapeutic effects. Moreover, molecular docking, molecular dynamics, and MST results indicated that Saikosaponin C (SSc), the major component of Bc, has a strong affinity for SIRT6. Cell experiments confirmed that SSc (25 μM) significantly improved lipid deposition and redox imbalance in MAFLD models, exhibiting SIRT6-dependent efficacy.</div></div><div><h3>Conclusion</h3><div>Bc alleviates MAFLD by activating SIRT6 through its core component SSc. This activation, via SIRT6-mediated histone deacetylation, enhances PPARα/NRF2-driven metabolic-redox homeostasis, establishing the Bc-SSc-SIRT6 axis as a therapeutic target.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157905"},"PeriodicalIF":8.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Da-Bu-Yin-Wan rescues cognitive deficits in aging and Alzheimer’s disease models by Wnt/β-catenin-dependent restoration of lysosomal acidification","authors":"Haijun Zhang ,&nbsp;Hao Zhang ,&nbsp;Meihuan Zhao ,&nbsp;Wenjun Luo ,&nbsp;Simin Chen ,&nbsp;Ping Wang ,&nbsp;Xiao Liu ,&nbsp;Shijun Xu","doi":"10.1016/j.phymed.2026.157916","DOIUrl":"10.1016/j.phymed.2026.157916","url":null,"abstract":"<div><h3>Background</h3><div>Lysosomal acidification deficits are increasingly recognized as a convergent pathological mechanism driving both age-related cognitive decline (ARCD) and early Alzheimer's disease (AD) progression, creating a self-reinforcing cycle of cellular aging and Aβ dyshomeostasis. Despite demonstrated neuroprotective effects of Da-Bu-Yin-Wan (DBYW) in Parkinson's disease models, its therapeutic potential for lysosomal dysfunction in ARCD and AD remains an uncharted area of investigation.</div></div><div><h3>Purpose</h3><div>This present work aimed to elucidate the mechanistic basis by which DBYW mitigates both ARCD and AD pathology through functionally rescuing impaired lysosomal acidification.</div></div><div><h3>Methods</h3><div>Cell-based D-galactose and Aβ-induced in BV2 cells to study lysosomal acidification. Molecular analyses combined immunofluorescence localization studies with quantitative immunoblotting of lysosomal and Wnt signaling proteins. <em>In vivo</em>, DBYW treatment effects were systematically evaluated in both D-gal-induced and APP/PS1 transgenic models using cognitive behavioral followed by immunohistochemical and biochemical assessment of brain tissues lysosomal parameters and Wnt signaling activity.</div></div><div><h3>Results</h3><div>DBYW attenuated the mechanistic basis of ARCD and AD pathology by functionally rescuing impaired lysosomal acidification. Overexpression of β-catenin could modulate D-galactose or Aβ-induced dysregulation of the Wnt/β-catenin pathway and restore lysosomes with abnormal acidification, while DBYW could regulate lysosomal function by promoting Wnt/β-catenin signaling. In addition, in D-gal-induced aging and AD model mice, DBYW treatment activated Wnt/β-catenin signaling to restore lysosomal acidification, while spatial memory deficits in ARCD and AD models were improved, and pathology in mouse attenuation and APP/PS1 mouse brain tissue was inhibited.</div></div><div><h3>Conclusion</h3><div>DBYW shows a potential dual efficacy in improving cognitive decline in ARCD and AD models. It makes DBYW a promising disease-modifying intervention targeting the shared lysosomal pathophysiology of aging-associated neurodegeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157916"},"PeriodicalIF":8.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetagitrin targets EIF3D to activate NCOA4-mediated ferritinophagy-dependent ferroptosis for the treatment of non-small cell lung cancer","authors":"Xinglinzi Tang ,&nbsp;Feiyan Wu ,&nbsp;Huijuan Rao ,&nbsp;Xinyi Luo ,&nbsp;Guixing Zhang ,&nbsp;Xin Lai ,&nbsp;Caizhi Li ,&nbsp;Jiansong Fang ,&nbsp;Hang Li","doi":"10.1016/j.phymed.2026.157914","DOIUrl":"10.1016/j.phymed.2026.157914","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancer. Although traditional treatment methods such as surgery, chemotherapy, and radiotherapy can extend patient survival to some extent, they still present significant challenges due to their limited efficacy and substantial side effects. Ferroptosis, a form of iron-dependent programmed cell death, has been shown to exhibit considerable potential in the treatment of NSCLC. However, the molecular mechanisms underlying ferroptosis and how to safely and effectively induce it remain to be fully explored. This study aims to investigate the mechanism by which the natural flavonoid compound Quercetagitrin (Que) regulates the ferritinophagy-ferroptosis pathway to suppress NSCLC and to identify its molecular targets.</div></div><div><h3>Methods</h3><div>This study evaluated the selective toxicity of Que against NSCLC cells (A549, PC9) and normal lung epithelial cells (BEAS-2B) using <em>in vitro</em> assays, including CCK-8, colony formation, and flow cytometry. Key pathways related to ferritinophagy and ferroptosis were identified through transcriptomic analysis and KEGG pathway analysis. Fluorescence imaging, Western blot (WB) and BODIPY C11 staining were used to assess the levels of ferritinophagy and ferroptosis in cells. Limited proteolysis-mass spectrometry (LiP-MS) and molecular dynamics simulations were employed to identify the direct targets of Que. Gene knockdown and overexpression experiments were conducted to verify that Que targets eukaryotic translation initiation factor 3 subunit D (EIF3D) and regulates the activation of nuclear receptor coactivator 4 (NCOA4) -mediated ferritinophagy. <em>In vivo</em> experiments using xenograft mouse models assessed the antitumor effect and safety of Que.</div></div><div><h3>Results</h3><div>Que selectively inhibited the proliferation and colony formation of NSCLC cells while showing minimal toxicity to normal lung epithelial cells. It promoted the release of Fe²⁺ and lipid peroxidation by activating the NCOA4-dependent ferritinophagy pathway, while simultaneously inhibiting the expression of ferroptosis markers such as glutathione peroxidase 4 (GPX4). LiP-MS and molecular dynamics simulations confirmed EIF3D as a direct target of Que. Knockdown of EIF3D mimicked the antitumor effect of Que, whereas overexpression of EIF3D diminished its antitumor effect. <em>In vivo</em>, Que significantly inhibited tumor growth without observable toxicity, accompanied by upregulation of NCOA4 and LC3 II, and downregulation of EIF3D and GPX4.</div></div><div><h3>Conclusion</h3><div>Que exerts significant antitumor effects in NSCLC by targeting EIF3D to activate NCOA4-mediated ferritinophagy and ferroptosis. This study reveals a novel mechanism involving the EIF3D-NCOA4 axis in the regulation of ferritinophagy-dependent ferroptosis, providing a potential therapeutic strategy for the treatment of NSCLC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157914"},"PeriodicalIF":8.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}