Phytomedicine最新文献

{"title":"Huang-Lian-Jie-Du decoction inhibits CD4+ T cell infiltration into CNS in MCAO rats by regulating BBB","authors":"Congai Chen ,&nbsp;Changxiang Li ,&nbsp;Xin Lan ,&nbsp;Zilin Ren ,&nbsp;Yuxiao Zheng ,&nbsp;Dan Chen ,&nbsp;Wenxiu Xu ,&nbsp;Youxiang Cui ,&nbsp;Xueqian Wang ,&nbsp;Fafeng Cheng ,&nbsp;Qingguo Wang","doi":"10.1016/j.phymed.2025.156607","DOIUrl":"10.1016/j.phymed.2025.156607","url":null,"abstract":"<div><h3>Background</h3><div>Stroke, especially ischemic stroke (IS), represents a major global health challenge due to its high incidence, disability, mortality, recurrence, and economic impact. The limited therapeutic window for thrombolysis underscores the need for new treatments. The blood-brain barrier (BBB), which protects the brain, becomes compromised following ischemia-reperfusion injury, allowing peripheral immune cell infiltration and subsequent neuroinflammation. Huang-Lian-Jie-Du Decoction (HLJDT), a traditional formula with significant neuroprotective effects demonstrated in preliminary studies and literature reviews, has not yet been fully explored for its potential to inhibit peripheral immune cell infiltration through BBB protection.</div></div><div><h3>Purpose</h3><div>This study aims to: (1) Evaluate the efficacy of HLJDT in treating MCAO. (2) Observe the regulatory effect of HLJDT on the infiltration of CD4+ T cells into the central nervous system. (3) Investigate the effect of HLJDT on the Wnt/β-Catenin Signaling Pathway.</div></div><div><h3>Methods</h3><div>A focal MCAO reperfusion model will be used to evaluate HLJDT's effects on neurological function (Zea Longa and Garcia scores), infarction volume (TTC staining), and pathological changes (HE and NISSL staining). Immune-inflammatory responses will be assessed using ELISA for cytokines, flow cytometry for T lymphocyte distribution, and immunofluorescence staining for CD4+ T cell infiltration. The interaction of T cell antigens (LFA-1) and endothelial adhesion molecules (ICAM-1) will be studied with ELISA and immunofluorescence. BBB protection will be evaluated with Evans blue staining and transmission electron microscopy. Mechanisms of T cell infiltration will be examined using transmission electron microscopy and Western blotting (WB) for key proteins. Additionally, the impact of HLJDT on the Wnt/β-catenin pathway will be assessed with WB.</div></div><div><h3>Results</h3><div>HLJDT significantly improves neurological scores, reduces infarction volume, and mitigates pathological damage. It balances CD4+ T cell responses by inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory ones, reducing CD4+ T cell CNS infiltration. HLJDT inhibits LFA-1/ICAM-1 interactions. It can also inhibit CD4+ T cell infiltration by repairing paracellular and transcellular structures of the BBB, with the Wnt/β-catenin signaling pathway playing a key role in this process.</div></div><div><h3>Conclusion</h3><div>We have innovatively demonstrated for the first time that HLJDT can regulate the balance between peripheral and central immune inflammation. It inhibits LFA-1/ICAM-1-mediated cell adhesion and, by modulating the Wnt/β-catenin pathway, improves the paracellular and transcellular structures of the blood-brain barrier, thereby suppressing CD4+ T cell infiltration and providing multifaceted protective effects for MCAO rats.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156607"},"PeriodicalIF":6.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674443","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":"The roles of algal polysaccharides in modulating tumor immune microenvironment","authors":"Yinfeng Wu ,&nbsp;Nan Jia ,&nbsp;Jingyu Sun ,&nbsp;Wei Liao ,&nbsp;Jingxiang Xu ,&nbsp;Weichao Chen ,&nbsp;Chao Zhao","doi":"10.1016/j.phymed.2025.156610","DOIUrl":"10.1016/j.phymed.2025.156610","url":null,"abstract":"<div><h3>Background</h3><div>Polysaccharides from algae provide a range of biology and health benefits. Lately, there has been a significant interest in how algal polysaccharides affect the immune microenvironment around tumors.</div></div><div><h3>Purpose</h3><div>To elucidate the subtle interactions between algal polysaccharides and the tumor immune microenvironment to further understand the medicinal potential of algal polysaccharides.</div></div><div><h3>Study design</h3><div>To give a summary of the sources, bioactivities and characteristics of the tumor immune microenvironment of algal polysaccharides, and to analyze alteration of the immunological milieu surrounding tumors by algal polysaccharides and their potential as immunomodulators of chemotherapeutic agents.</div></div><div><h3>Methods</h3><div>Search popular academic search engines using selected keywords for articles ending before September 2024 using selected keywords Google Scholar, PubMed, ScienceDirect, Scopus, Web of Science, Springer, and official websites.</div></div><div><h3>Results</h3><div>Algal polysaccharides can fight tumors by changing how immune cells work and affecting inflammation in different ways. Moreover, algal polysaccharides have shown promise in mitigating the adverse effects associated with conventional cancer treatments, such as chemotherapy. Algal polysaccharides, through their immunomodulatory effects, can alleviate some of these side effects, leading to an enhanced overall treatment outcome.</div></div><div><h3>Conclusion</h3><div>As research continues to uncover the underlying mechanisms of their antitumor effects, algal polysaccharides are poised to become a vital component in the development of novel cancer treatments, providing new hope for patients and advancing the field of oncology.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156610"},"PeriodicalIF":6.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609483","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":"Naoqing formula alleviates cerebral ischemia/reperfusion injury induced inflammatory injury by regulating Csf3 mediated JAK/STAT pathway and macrophage polarization","authors":"Yujun Ye ,&nbsp;Zhaowei Rao ,&nbsp;Xuexin Xie ,&nbsp;Yingxin Liu ,&nbsp;Lingling Qiu ,&nbsp;Qing Liu ,&nbsp;Xuliang Weng ,&nbsp;Chengyin Wang ,&nbsp;Yiming Bi ,&nbsp;Ting Zeng","doi":"10.1016/j.phymed.2025.156626","DOIUrl":"10.1016/j.phymed.2025.156626","url":null,"abstract":"<div><h3>Background</h3><div>Upon cerebral ischemia/reperfusion injury (CIRI), the brain tissue experiences excessive inflammatory responses, which fuel the activation of immune cells, thereby intensifying cellular damage and inflammatory reactions. Naoqing formula (NQ), a traditional Chinese medicinal compound formulated with musk as the primary component, has been extensively utilized in China for the clinical treatment of ischaemic stroke (IS).</div></div><div><h3>Purpose</h3><div>The precise pharmacological mechanism underlying NQ's efficacy in managing IS remains elusive. In this study, we investigate the protective effect and molecular mechanism of NQ against CIRI.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were utilized to investigate the protective effects of NQ (130, 260 and 520mg/kg) against middle cerebral artery occlusion (MCAO) induced CIRI and the underlying mechanism. Employing molecular biology techniques, transcriptomics, proteomics, and network pharmacological analyses, the study assessed the role of NQ in the inflammatory response of neuronal cells by establishing a model for neuronal cell and microglia inflammatory injury induced by oxygen-glucose deprivation/reperfusion (OGD/R) and lipopolysaccharide (LPS) stimulation.</div></div><div><h3>Results</h3><div>NQ demonstrated significant efficacy in mitigating neuronal damage and cerebral infarction induced by CIRI, achieved through the enhancement of cortical blood flow. Transcriptomic and network pharmacological analyses revealed that NQ mitigated the inflammatory damage caused by CIRI by modulating the Csf3-mediated JAK/STAT pathway. Proteomic analysis further corroborated this finding, indicating that NQ reduced the impact of CIRI by regulating macrophage polarization. Notably, in CIRI mice treated with NQ, there was a notable downregulation of Csf3, JAK2, STAT3, and STAT6, along with a co-localization of Csf3 and CD206. These observations suggested that NQ inhibited the activation of the JAK/STAT pathway and exerted its anti-inflammatory effects by orchestrating the transition of macrophages from the M1 phenotype to the M2 phenotype, triggered by Csf3. Consistent with the <em>in vivo</em> findings, NQ also inhibited the activation of the JAK/STAT pathway in neuronal cells and microglial polarization <em>in vitro</em>, thereby protecting against OGD/R- and LPS-induced inflammatory injury.</div></div><div><h3>Conclusion</h3><div>This study confirmed that NQ prevented CIRI induced inflammatory injury by inhibiting Csf3-mediated activation of the JAK/STAT pathway and modulating Csf3-mediated macrophage polarization. This study provided a new perspective on the use of NQ in the treatment of IS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156626"},"PeriodicalIF":6.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective-compounds of Jinshui Huanxian Formula acts as an SRC inhibitor to inhibit HK2-mediated H3K18 lactation and improve pulmonary fibrosis","authors":"Jiaping Zheng ,&nbsp;Yan Du ,&nbsp;Wenbo Shao ,&nbsp;Jiansheng Li ,&nbsp;Peng Zhao ,&nbsp;Qin Zhang","doi":"10.1016/j.phymed.2025.156628","DOIUrl":"10.1016/j.phymed.2025.156628","url":null,"abstract":"<div><h3>Background</h3><div>The Active Ingredient Composition of Jinshui Huanxian Formula (ECC-JHF) consists of five active ingredients: icariin, isoliquiritigenin, nobiletin, peimine, and paeoniflorin, which demonstrate notable therapeutic effects on pulmonary fibrosis.</div></div><div><h3>Purpose</h3><div>Inhibition of glycolysis has been demonstrated to be effective in treating experimental idiopathic pulmonary fibrosis (IPF). This research seeks to explore the impact of aerobic glycolysis on the mitigation of pulmonary fibrosis through ECC-JHF.</div></div><div><h3>Methods</h3><div>A pulmonary fibrosis mouse model was generated through the administration of bleomycin (Bleomycin). The degree of pulmonary fibrosis was analyzed through hematoxylin and eosin (H&amp;E) staining as well as Masson's trichrome staining. Western Blot (WB), Immunofluorescence (IF), and real-time quantitative PCR (Q-PCR) assay for fibroblast activation markers and glycolysis-related genes in lung tissues. The Lactic Acid (LA) Content Assay Kit was employed to quantify lactate concentrations in lung tissues and fibroblast cultures. Immunoprecipitation (IP) was applied to detect lactylated modified protein levels, and mass spectrometry (MS) was used to analyze lactate substrate profiles in fibroblasts. WB was employed to detect the lactate modification level of histone H3K18 (H3K18la). The targets of ECC-JHF were analyzed using network pharmacology, while molecular docking and cellular enthusiasm transfer analysis (CETSA) examined the binding of ECC-JHF to SRC. The influence of ECC-JHF on SRC activation was assessed using WB. SRC small interfering RNA (siSRC) was designed and transfected into L929 cells to validate the function of SRC in the inhibition of fibroblast activation by ECC-JHF.</div></div><div><h3>Results</h3><div>In BLM-induced pulmonary fibrosis mice, ECC-JHF significantly reduced alveolar inflammation and collagen deposition. In lung tissues and fibroblasts, ECC-JHF notably inhibited the expression of HK2, lactate levels, and lactylated modifying proteins. IP-MS and WB analyses showed that ECC-JHF significantly reduced H3K18la levels. Network pharmacology analysis, molecular docking and CETSA results indicated that SRC serves as a key target for ECC-JHF. siSRC effectively mitigated the impact of ECC-JHF on the expression of HK2, levels of H3K18la, and the activation of fibroblasts.</div></div><div><h3>Conclusion</h3><div>ECC-JHF may improve pulmonary fibrosis by inhibiting SRC activation, blocking HK2-mediated lactate production, down-regulating H3K18la levels, and inhibiting fibroblast activation. Our results serve as a significant reference for the advancement of ECC-JHF and the exploration of IPF.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156628"},"PeriodicalIF":6.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628127","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":"Dietary essential oil components: A systematic review of preclinical studies on the management of gastrointestinal diseases","authors":"Rajiv Gandhi Gopalsamy ,&nbsp;Poovathumkal James Antony ,&nbsp;Kumaraswamy Athesh ,&nbsp;Varghese Edwin Hillary ,&nbsp;Monalisa Martins Montalvão ,&nbsp;Govindasamy Hariharan ,&nbsp;Lucas Alves da Mota Santana ,&nbsp;Lysandro Pinto Borges ,&nbsp;Ricardo Queiroz Gurgel","doi":"10.1016/j.phymed.2025.156630","DOIUrl":"10.1016/j.phymed.2025.156630","url":null,"abstract":"<div><h3>Background</h3><div>The gut is responsible for the digestion and absorption of nutrients, immune regulation, and barrier function. However, factors like poor diet, stress, and infection, can disrupt the balance of the gut microbiota and lead to intestinal inflammation and dysfunction.</div></div><div><h3>Purpose</h3><div>This systematic review aims to evaluate the effects of dietary plants-derived essential oil components on gut health and intestinal functions in animal models.</div></div><div><h3>Methods</h3><div>The literature was gathered from the Scopus, Web of Science, PubMed, and Embase databases by using related search terms, such as \"dietary plants\", \"dietary sources\", \"essential oils\", \"gut health\", \"intestine\", \"anti-inflammatory\", \"antioxidant\", and \"gut microbiota\".</div></div><div><h3>Results</h3><div>The results indicate that plant-derived dietary essential oil components, such as butyrolactone-I, carvacrol, cinnamaldehyde, citral, D-limonene, eugenol, farnesol, geraniol, indole, nerolidol, oleic acid, thymol, trans-anethole, vanillin, α-bisabolol, α-linolenic acid, α-pinene, α-terpineol, β-carotene, β-caryophyllene, and β-myrcene have been found to regulate gut health by influencing vital signalling pathways associated with inflammation. Dietary essential oil components modulate the expression of tumor necrosis factor alpha, interleukin 1 beta (IL-1β), interleukin (IL)-6, IL-10, inducible nitric oxide synthase, cyclooxygenase-2, toll-like receptor-4, matrix metalloproteinase, and interferon gamma in mitigating gut inflammation. The primary signalling molecules controlled by these molecules were AMP-activated protein kinase (AMPK), protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase, mitogen-activated protein kinase, myeloid differentiation primary response 88, nuclear factor erythroid-2-related factor-2, and phosphoinositide 3-kinase (PI3K). Moreover, these phytochemicals have been shown to improve glucose homeostasis by regulating glucose transporter 4, glucagon-like peptide-1, peroxisome proliferator-activated receptor gamma, nuclear factor kappa B, AMPK, PI3K, and uncoupling protein-1. They can also reduce thiobarbituric acid reactive substance, malondialdehyde, and oxidative stress and enhance superoxide dismutase, catalase, and glutathione peroxidase levels.</div></div><div><h3>Conclusion</h3><div>In conclusion, dietary plants-derived essential oil components have the potential to mitigate inflammation and oxidative stress in the gut. However, additional clinical investigations are necessary to confirm their complete potential in improving human gut health functions.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156630"},"PeriodicalIF":6.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620653","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":"Guizhi Fuling decoction protects against bone destruction via suppressing exosomal ERK1 in multiple myeloma","authors":"Manya Yu ,&nbsp;Jie Zhang ,&nbsp;Jiaqi Fu ,&nbsp;Suzhen Li ,&nbsp;Xing Cui","doi":"10.1016/j.phymed.2025.156627","DOIUrl":"10.1016/j.phymed.2025.156627","url":null,"abstract":"<div><h3>Background</h3><div>Myeloma-related bone disease (MBD) is a common complication of multiple myeloma (MM) that deteriorates patients' quality of life and affects overall survival. Modulating the interaction between myeloma cells and the bone marrow microenvironment may offer therapeutic potential. While certain natural medicines may regulate bone homeostasis by directly targeting osteoclasts or osteoblasts, few studies have explored the effects of intervening in myeloma cells on osteoclasts, particularly through the role of exosomes.</div></div><div><h3>Purpose</h3><div>To investigate the inhibitory effect of <em>Guizhi Fuling</em> Decoction (GZFL) on bone lesions formation induced by exosomes secreted by myeloma cells and provide evidence to support the clinical application of GZFL in treating MBD.</div></div><div><h3>Methods</h3><div>TRAP staining and Von Kossa staining were used to evaluate the inhibition of GZFL on RANKL-induced osteoclastogenesis in vitro. Micro-CT and bone histomorphometric analyses were performed to identify the protective effect of GZFL on bone destruction in vivo. RNA immunoprecipitation (RIP), RNA-seq, and UHPLC-MS/MS were conducted to investigate the MBD targets of GZFL. A clinical trial was carried out to evaluate the efficacy of GZFL capsules in the treatment of MBD.</div></div><div><h3>Results</h3><div>The main bioactive components of GZFL, paeoniflorin, quercitrin and kaempferol, could target ERK1 and downregulate its expression in MM exosomes. In vitro, GZFL treatment inhibited the promoting effect of MM exosomes on osteoclast (OC) formation, bone resorption, and activated ERK1 expression. In vivo, GZFL prolonged survival rate, inhibited the exacerbation of bone lesions caused by MM exosomes and RANKL-induced ERK1 activation in mice model. Clinical data showed that GZFL capsule combined with bortezomib (Bortezomib) and dexamethasone (PD) significantly reduced the numeric rating scale, as well as the expression levels of ERK and RANKL in bone marrow. ERK1 levels exhibited a positive correlation with both the number of bone lesions and RANKL levels. Higher ERK1 expression indicated a worse prognosis.</div></div><div><h3>Conclusion</h3><div>GZFL inhibited MBD progression by reducing MM-derived exosomal ERK1, thereby suppressing RANKL-induced ERK1 activation and the downstream OC formation. GZFL combined with PD regimen had good clinical efficacy and safety in the treatment of MBD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156627"},"PeriodicalIF":6.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628023","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":"α-Hederin causes ferroptosis in triple-negative breast cancer through modulating IRF1 to suppress GPX4","authors":"Xue Wu ,&nbsp;Lingli Jin ,&nbsp;Disuo Ren ,&nbsp;Shaolong Huang ,&nbsp;Xinyu Meng ,&nbsp;Zhixuan Wu ,&nbsp;Chaoyue Lv ,&nbsp;Jiatong Ru ,&nbsp;Heyu Zhang ,&nbsp;Shuwei Zhang ,&nbsp;Jingxia Bao ,&nbsp;Ouchen Wang ,&nbsp;Erjie Xia","doi":"10.1016/j.phymed.2025.156611","DOIUrl":"10.1016/j.phymed.2025.156611","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer ranks first in the global incidence rate of cancer among women. Triple-negative breast cancer (TNBC) is considered to be the most dangerous type because of the lack of specific therapeutic targets and rapid progression. The emergence of ferroptosis provides a new therapeutic perspective for TNBC. α-Hederin is a triterpenoid saponin derived from the traditional Chinese medicine Ivy, which has been proven to have anti-cancer effects on various cancers, but its efficacy and mechanism of inducing ferroptosis in TNBC remain to be further clarified.</div></div><div><h3>Object</h3><div>To investigate the effect and mechanism of α-Hederin induced ferroptosis in TNBC.</div></div><div><h3>Method</h3><div>Cell viability was measured by CCK-8 assay, and cell proliferation and migration were evaluated by clone assay and scratch assay. The effect of α-Hederin on TNBC cell apoptosis was assessed by flow cytometry. Transcriptomics searches for critical pathways. Intracellular and lipid reactive oxygen species and Fe²⁺<strong>and Fe</strong> were detected by DCFH-DA probe, FerroOrange fluorescent probe and C11-BODIPY fluorescent probe, and the contents of malondialdehyde and reduced glutathione were detected by MDA and GSH kits. Erastin was used as a positive control for ferroptosis and Ferrrostatin-1(Fer-1) as an inhibitor. The relationship between α-Hederin and GPX4, IRF was analyzed by western blot and si-RNA, and the association was further confirmed by molecular simulation docking, external SPR experiments, and luciferase experiments. Constructing xenograft mouse models and human derived organoid models to evaluate the anti-TNBC efficacy of α-Hederin, and verifying the efficacy and ferroptosis mechanism of the drug <em>in vivo</em> through HE staining and IHC.</div></div><div><h3>Result</h3><div>α-Hederin significantly inhibited the progression of TNBC. <em>In vitro</em>, α-Hederin decreased cancer cell viability through ferroptosis, increased glutathione degradation and MDA production, and promoted intracellular Fe²⁺ and ROS production, whereas Fer-1, an ferroptosis inhibitor, reversed this effect. Mechanistically, molecular docking and SPR experiments showed binding of α-Hederin to the key regulator IRF1, and knockdown/overexpression of IRF1 significantly affected the expression of GPX4, a downstream target of the ferroptosis pathway. <em>In vivo</em>, α-Hederin prevented tumor growth in xenograft and organoid models via the IRF1/GPX4 axis.</div></div><div><h3>Conclusion</h3><div>We proved for the first time in this research that α-Hederin exerts anti-TNBC effects through a novel IRF1/GPX4 ferroptosis pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156611"},"PeriodicalIF":6.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704606","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":"Raspberry ameliorates renal fibrosis in rats with chronic kidney disease via the PI3K/Akt pathway","authors":"Jingjing Hu ,&nbsp;Xingyuan Pang ,&nbsp;Xiao Liang ,&nbsp;Xinyuan Shao ,&nbsp;Qijun Xia ,&nbsp;Jianwen Sun ,&nbsp;Yuxiao Wang ,&nbsp;Guichun Wang ,&nbsp;Shuhan Li ,&nbsp;Liangping Zha ,&nbsp;Jian Guo ,&nbsp;Chengjun Peng ,&nbsp;Peng Huang ,&nbsp;Yang Ding ,&nbsp;Cheng Jin ,&nbsp;Ning He ,&nbsp;Yuzhe Huang ,&nbsp;Shuangying Gui","doi":"10.1016/j.phymed.2025.156589","DOIUrl":"10.1016/j.phymed.2025.156589","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis is a hallmark of chronic kidney disease (CKD). In traditional Chinese medicine, <em>Rubus chingii</em> Hu (raspberry) is believed to have kidney-tonifying properties. However, whether raspberry can effectively treat CKD, along with the specific active compounds and underlying mechanisms, remains unclear.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the potential of raspberries in treating CKD and elucidate the mechanisms involved.</div></div><div><h3>Methods</h3><div>CKD model was established in rats using adenine. The effects of raspberry treatment on CKD were assessed through macroscopic observations and pathological changes in the kidney. The expression of fibrotic proteins in renal tissues was analyzed to evaluate the impact of raspberry on renal fibrosis. Data mining combined with compositional analysis were employed to identify the active ingredients, targets, and pathways of raspberry that may improve CKD. Subsequently, Western blotting and immunofluorescence analysis were conducted to confirm the involvement of the PI3K/AKT signaling pathway in the renoprotective mechanism of raspberry.</div></div><div><h3>Results</h3><div>Raspberry treatment significantly alleviated renal pathological damage, fibrosis and inflammation in model rats, showing effects comparable to irbesartan (Avapro). Chemical composition analysis and network pharmacology predicted AKT1 as the core target, and the PI3K/AKT pathway plays a pivotal role in mediating the therapeutic effects of raspberry extract in CKD. Molecular docking studies further confirmed that active compounds in raspberry have a strong binding affinity with AKT1. Western blotting and immunofluorescence results demonstrated that raspberry inhibited phosphorylation, thereby suppressing the PI3K/AKT pathway, leading to its antifibrotic effect on the kidney.</div></div><div><h3>Conclusion</h3><div>Raspberry was firstly discovered to potentially treat CKD by alleviating renal fibrosis through inhibition of the PI3K/AKT pathway. Raspberry, as a medicinal and edible traditional herb, could serve as a promising therapeutic agent or health supplement for improving renal fibrosis and slowing CKD progression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156589"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563527","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":"Mitochondrial dynamics and metabolism in macrophages for cardiovascular disease: A review","authors":"Yi-lang Zhong ,&nbsp;Chen-qin Xu ,&nbsp;Ji Li ,&nbsp;Zhi-qiang Liang ,&nbsp;Miao-miao Wang ,&nbsp;Chao Ma ,&nbsp;Cheng-lin Jia ,&nbsp;Yong-bing Cao ,&nbsp;Jian Chen","doi":"10.1016/j.phymed.2025.156620","DOIUrl":"10.1016/j.phymed.2025.156620","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondria regulate macrophage function, affecting cardiovascular diseases like atherosclerosis and heart failure. Their dynamics interact with macrophage cell death mechanisms, including apoptosis and necroptosis.</div></div><div><h3>Purpose</h3><div>This review explores how mitochondrial dynamics and metabolism influence macrophage inflammation and cell death in CVDs, highlighting therapeutic targets for enhancing macrophage resilience and reducing CVD pathology, while examining molecular pathways and pharmacological agents involved.</div></div><div><h3>Study design</h3><div>This is a narrative review that integrates findings from various studies on mitochondrial dynamics and metabolism in macrophages, their interactions with the endoplasmic reticulum (ER) and Golgi apparatus, and their implications for CVDs. The review also considers the potential therapeutic effects of pharmacological agents on these pathways.</div></div><div><h3>Methods</h3><div>The review utilizes a comprehensive literature search to identify relevant studies on mitochondrial dynamics and metabolism in macrophages, their role in CVDs, and the effects of pharmacological agents on these pathways. The selected studies are analyzed and synthesized to provide insights into the complex relationships between mitochondria, the ER, and Golgi apparatus, and their implications for macrophage function and fate.</div></div><div><h3>Results</h3><div>The review reveals that mitochondrial metabolism intertwines with cellular architecture and function, particularly through its intricate interactions with the ER and Golgi apparatus. Mitochondrial-associated membranes (MAMs) facilitate Ca2+ transfer from the ER to mitochondria, maintaining mitochondrial homeostasis during ER stress. The Golgi apparatus transports proteins crucial for inflammatory signaling, contributing to immune responses. Inflammation-induced metabolic reprogramming in macrophages, characterized by a shift from oxidative phosphorylation to glycolysis, underscores the multifaceted role of mitochondrial metabolism in regulating immune cell polarization and inflammatory outcomes. Notably, mitochondrial dysfunction, marked by heightened reactive oxygen species generation, fuels inflammatory cascades and promotes cell death, exacerbating CVD pathology. However, pharmacological agents such as Metformin, Nitazoxanide, and Galanin emerge as potential therapeutic modulators of these pathways, offering avenues for mitigating CVD progression.</div></div><div><h3>Conclusion</h3><div>This review highlights mitochondrial dynamics and metabolism in macrophage inflammation and cell death in CVDs, suggesting therapeutic targets to improve macrophage resilience and reduce pathology, with new pharmacological agents offering treatment opportunities.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156620"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578404","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":"Study on the pharmacodynamic substances and mechanism of hepatoprotection of Acanthus ilicifolius Linn.","authors":"Mengqi Zhang ,&nbsp;Dahu Zhang ,&nbsp;Xia Ren ,&nbsp;Shijun Yue ,&nbsp;Jinyue Sun ,&nbsp;Ningyang Li ,&nbsp;Shujin Bai ,&nbsp;Changyun Wang ,&nbsp;Chao Liu","doi":"10.1016/j.phymed.2025.156526","DOIUrl":"10.1016/j.phymed.2025.156526","url":null,"abstract":"<div><h3>Background</h3><div>The coastal wetland mangrove plant <em>Acanthus ilicifolius</em> l. (AI) is used as traditional medicine for liver protection and liver fibrosis treatment, but the pharmacodynamics of the hepatoprotective substance and the mechanisms of liver protection are not clear.</div></div><div><h3>Purpose</h3><div>This work aimed to assess the liver-protective ability of AI and elucidate the pharmacodynamics of the hepatoprotective substance of AI responsible for its liver activity.</div></div><div><h3>Study Design and Methods</h3><div>This study first appraised the hepatoprotective activity of the alcohol extract of AI. To identify the hepatoprotective substance in AI, network topology and the contribution index were comprehensively analyzed and screened. The screened medicinal substances, acteoside (ACT) and isoacteoside (IACT), were tested for hepatoprotective activity using mouse liver damage model and l-02 hepatocyte injury model, and metabolomics was employed to explore the mechanism of liver protection.</div></div><div><h3>Results</h3><div>AI could restore the biochemical indicators of liver damage induced by CCl₄ to normal conditions. The phenylethanoid glycoside compounds ACT and IACT, are the hepatoprotective substances of AI. ACT protects the liver tissue by regulating α-linolenic acid metabolism, glycerophospholipid metabolism, and amino acid–related pathway.</div></div><div><h3>Conclusion</h3><div>This research provides basic information of the research and development of liver-protective effects of AI and ACT.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156526"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592907","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}