Phytomedicine最新文献

{"title":"Ligustilide covalently binds to Cys254 of the creatine kinase, M-type protein, ameliorating acute myocardial ischemia by enhancing the creatine phosphate level","authors":"Kaixue Zhang,&nbsp;Guoqing Luan,&nbsp;Jin Zhang,&nbsp;Shilong Wang,&nbsp;Min Jiang,&nbsp;Gang Bai","doi":"10.1016/j.phymed.2025.156532","DOIUrl":"10.1016/j.phymed.2025.156532","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial ischemia (MI) threatens the health of middle-aged and older adults by reducing cardiac oxygen supply and function. Current therapies, including vasodilation, thrombolysis, and interventions, focus on relieving symptoms and improving blood flow but do not adequately address underlying energy metabolism issues. Ligustilide exerts a protective effect on the cardiovascular system and holds the potential for ameliorating MI; however, there is currently no systematic elucidation of ligustilide's target and action mechanism for MI.</div></div><div><h3>Purpose</h3><div>This study aimed to comprehensively assess ligustilide's potential targets for improving acute MI and elucidate its underlying mechanism.</div></div><div><h3>Methods</h3><div>The therapeutic effects of ligustilide were evaluated at doses of 30, 15, and 7.5 mg/kg over 7 days in a murine model of acute MI induced by isoproterenol hydrochloride. The putative target protein was identified through target fishing, in-gel imaging, and thermal shift assay (TSA), followed by tissue and cell localization studies <em>via</em> a ligustilide probe. The interaction sites between ligustilide and the target protein were elucidated using protein profiling, molecular docking, and TSA at the protein level. Subsequently, knockdown and reconstruction tests were employed at the cellular level to identify the functionally active sites where ligustilide binds to the target protein. Finally, molecular docking and molecular dynamics simulations were conducted to elucidate the underlying mechanism by which ligustilide enhances creatine kinase, M-type (CKMM) protein activity.</div></div><div><h3>Results</h3><div>The covalent bonding of ligustilide in cardiac tissue enhances the therapeutic effect on acute MI in mice. For the first time, we found ligustilide specifically targets Cys254 of the CKMM protein following epoxidation. This irreversible binding effectively reduces the proximity between creatine and ATP, promoting creatine phosphorylation and ultimately increasing the creatine phosphate (CP) level by 9.50 % to 19.31 %. The accumulation of CP alleviates MI by enhancing energy metabolism, mitigating oxidative stress, and suppressing inflammatory responses.</div></div><div><h3>Conclusions</h3><div>Our study unveiled ligustilide as a CKMM activator, which effectively enhances the content of CP and mitigates acute MI. The findings significantly contribute to advancing our understanding of ligustilide's function for myocardial protection while proposing a novel activation mechanism of CKMM to improve MI. And the insight into the covalent regulation of the active pocket on CKMM may lead to an alternative therapeutic strategy against acute MI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156532"},"PeriodicalIF":6.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473907","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":"5-hydroxymethylfurfural attenuates osteoarthritis by upregulating of glucose metabolism in chondrocytes","authors":"Xinyu Wang ,&nbsp;Xiaolong Han ,&nbsp;Jinjin Ma ,&nbsp;Ruogu Zhang ,&nbsp;Kaiao Zou ,&nbsp;Xucheng Wang ,&nbsp;Wenhua Yuan ,&nbsp;Min Qiu ,&nbsp;Jiali Chen ,&nbsp;Yimin Yang ,&nbsp;Songfeng Hu ,&nbsp;Xiaofeng wang ,&nbsp;Hongting Jin ,&nbsp;Yuanbin Zhang ,&nbsp;Pinger Wang","doi":"10.1016/j.phymed.2025.156499","DOIUrl":"10.1016/j.phymed.2025.156499","url":null,"abstract":"<div><h3>Introduction</h3><div>5-HMF (5-hydroxymethylfurfural), an active constituent found in Radix Rehmanniae Preparata, a widely utilized traditional Chinese medicine for osteoarthritis (OA) treatment, exhibits notable therapeutic benefits in countering the catabolic and inflammatory responses of OA chondrocytes. Despite these promising effects, the underlying mechanisms of 5-HMF's action remain elusive, thereby impeding its broader clinical application and development.</div></div><div><h3>Objective</h3><div>To investigate the impact of 5-HMF on the progression of OA and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>In this study, Destabilization of the Medial Meniscus (DMM) was used to construct an OA model of C57BL/6 and transgenic mice in vivo, and interleukin -1β (IL-1β) was used to construct an OA model in vitro. Micro-CT and Alcnohistochemistry (IHC) and immunofluorescence (IF) were used to determine the eian Blue/Hematoxylin and Orange G (ABH/OG) staining were used to observe the morphological changes of joints. Western blot, Polymerase Chain Reaction (PCR), immuxpression levels of cartilage metabolic markers Collagen type II alpha 1 (Col2a1) and Matrix Metalloproteinase-13 (MMP13), as well as glucose transporter Glucose Transporter Type 1 (Glut1), glucose metabolic markers Hexokinase 1 (HK1) and Lactate Dehydrogenase A (LDHA). RNA-seq and Reactom analysis were used to predict the potential mechanism of 5-HMF in the treatment of OA.</div></div><div><h3>Results</h3><div>5-HMF demonstrates effective alleviation of OA progression, improvement of subchondral sclerosis and cartilage degeneration, particularly in the realm of cartilage protection, which is equivalent to that of celebrex. The protective effect of 5-HMF on cartilage is primarily attributed to its regulatory role in cartilage matrix metabolism, suppress the activity of MMP13 and enhance the expression of Col2a1 to delay cartilage injury. Moreover, RNA sequencing results indicate that 5-HMF's therapeutic effect on OA is closely linked to metabolism, specifically glucose metabolism. Our in vivo and in vitro experiments validate these findings. 5-HMF can counteract the decline in glucose metabolism induced by OA through the Glut1/HK1/LDHA signaling pathway. Furthermore, our findings confirm that Glut1 knockout mice with a DMM-induced OA model do not respond to 5-HMF treatment.</div></div><div><h3>Conclusion</h3><div>Our data reveal for the first time that 5-HMF may play a role in cartilage protection in the treatment of osteoarthritis by regulating glycolysis driven by Glut1/HK1/LDHA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156499"},"PeriodicalIF":6.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510093","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":"Apigenin alleviates inflammation as a natural IRAK4 inhibitor","authors":"Pianchou Gongpan ,&nbsp;Tingting Xu ,&nbsp;Yufei Zhang ,&nbsp;Kailong Ji ,&nbsp;Lingmei Kong ,&nbsp;Xue Wang ,&nbsp;Hongman Chen ,&nbsp;Qishi Song ,&nbsp;Yili Sun ,&nbsp;Chang-an Geng ,&nbsp;Jia Li","doi":"10.1016/j.phymed.2025.156519","DOIUrl":"10.1016/j.phymed.2025.156519","url":null,"abstract":"<div><h3>Background</h3><div>Uncontrolled inflammation is a key factor in the development of many diseases, and targeting pivotal kinases involved in the inflammatory response, such as interleukin-1 receptor-associated kinase 4 (IRAK4), holds promise for the treatment of inflammatory conditions. Apigenin (Api) is a popular element in numerous plants, possessing anti-inflammatory properties. Many studies have shown that Api modulates NF-κB signaling and MAPK cascade to reduce inflammation, but the exact mechanisms by which Api regulates these pathways remain unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to investigate the role of Api on acute inflammation and its specific mechanism in mediating inflammation.</div></div><div><h3>Methods</h3><div>The dextran sulfate sodium (DSS) induced ulcerative colitis (UC) model and LPS induced acute inflammation mouse model were established to investigate the anti-inflammatory effects of Api. Subsequently, the anti-inflammatory activity of Api was validated <em>in vitro</em> and <em>vivo</em> by RNA-seq, qPCR, Western blot, cytokine ELISA, immunofluorescence and histological analysis. A series of experiments were performed to study the effects of Api on IRAK4, including ADP-Glo™ kinase assay, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and molecular docking simulation. The targeting of Api to IRAK4 was verified by IRAK4 inhibitor and siRNA.</div></div><div><h3>Results</h3><div>Oral administration of Api significantly ameliorated inflammatory conditions in the LPS induced acute inflammation and DSS induced UC mouse models. Furthermore, Api inhibited the expression of interleukin and chemotactic factor genes and downregulated the immune response of macrophages at the transcriptome level. Mechanistically, Api acted as a novel IRAK4 inhibitor, inhibiting kinase activity by direct binding to IRAK4 (Kd = 4.78 μM) with an IC₅₀ of 1.74 μM, interfering with extracellular signaling to the NF-κB and MAPK pathways, and reducing the expression of pro-inflammatory factors in an IRAK4 dependent manner.</div></div><div><h3>Conclusion</h3><div>In this study, Api was identified for the first time as a natural IRAK4 inhibitor that suppresses cytokine signaling pathways and modulates the immune response at the level of the transcriptome. The results provided valuable insights into the specific mechanism of Api inhibition of inflammatory activation and shed light on opportunities for the development of novel IRAK4 inhibitors based on Api, which is found in various plants.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156519"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487401","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":"Targeting ferroptosis in the treatment of ulcerative colitis by traditional Chinese medicine: A novel therapeutic strategies","authors":"Ying Liu ,&nbsp;Jing-tian Zhang ,&nbsp;Meng Sun ,&nbsp;Jian Song ,&nbsp;Hai-Ming Sun ,&nbsp;Meng-Yang Wang ,&nbsp;Chun-Mei Wang ,&nbsp;Wei Liu","doi":"10.1016/j.phymed.2025.156539","DOIUrl":"10.1016/j.phymed.2025.156539","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of ulcerative colitis (UC) has been rising rapidly in recent years, and there is currently no effective method to prevent its recurrence. Owing to its long treatment duration, difficulty in treatment, prolonged remission, and high costs, it has attracted global attention. Exploring safe, effective, and sustainable treatment regimens has become an urgent global issue. Traditional Chinese medicine (TCM) has unique advantages such as low cost, low drug resistance, and fewer side effects, and has accumulated rich experience in the treatment of UC.</div></div><div><h3>Purpose</h3><div>Ferroptosis, as a new form of non-apoptotic cell death, is characterized by iron homeostatic imbalance and lipid peroxidation in the redox system. Studies have shown that inhibited ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of UC.</div></div><div><h3>Methods</h3><div>We conducted a systematic literature search with Google Scholar, PubMed, Web of Science, ScienceDirect and X-mol databases have been utilized to retrieve relevant literature up to October 2024, using keywords included ferroptosis, Inflammatory bowel disease (IBD), UC, Crohn's disease and TCM, Chinese traditional prescription, Chinese medicine extract and active ingredients. The existing literature was comprehensively studied and sorted out.</div></div><div><h3>Results</h3><div>Currently, UC is mainly treated with drugs, including corticosteroids, amino salicylates, biologics, and immunomodulators, but drug resistance and adverse reactions are common. Increasing evidence suggests that TCM may treat UC by interfering with ferroptosis. Scholars have confirmed that TCM can inhibit ferroptosis, and recent studies have shown that TCM can not only inhibit iron dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa, thus playing a role in the treatment of UC. This review explores the relevance of TCM intervention in ferroptosis and the treatment of UC, discusses the possible mechanisms of ferroptosis in UC, and aims to provide a basis for the diagnosis and treatment of UC.</div></div><div><h3>Conclusion</h3><div>It is revealed that TCM targeted ferroptosis has a good application prospect in the treatment of UC, providing a theoretical basis for elucidating the pathogenesis of UC and the study of TCM targeting ferroptosis regulating lipid metabolism in the treatment of UC, and providing a new perspective for the treatment of IBD in the future.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156539"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463631","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":"(+)-Borneol enhances the protective effect of edaravone against cerebral ischemia/reperfusion injury by targeting OAT3/P-gp transporters for drug delivery into the brain","authors":"Xin Wang ,&nbsp;Jun-jin Liu ,&nbsp;Xin-ru Zheng ,&nbsp;Ze-jia Zhou ,&nbsp;Jia-qi Duan ,&nbsp;Hai-yu Liu ,&nbsp;Yun-yun Shao ,&nbsp;Rui-gang Hou","doi":"10.1016/j.phymed.2025.156521","DOIUrl":"10.1016/j.phymed.2025.156521","url":null,"abstract":"<div><h3>Objectives</h3><div>Cerebral ischemia-reperfusion (CI/R) injury is a severe neurological condition associated with significant morbidity and mortality. Edaravone-dexborneol is a promising neuroprotective agent for alleviating CI/R injury, which composed of edaravone and (+)-borneol. Several studies have confirmed that combining edaravone with (+)-borneol can exert synergistic effects when compared to using edaravone alone. However, whether the synergistic effect is achieved through the enhanced cerebral delivery of edaravone facilitated by (+)-borneol remains unclear, and the potential binding targets need to be further explored.</div></div><div><h3>Methods</h3><div>Middle cerebral artery obstruction reperfusion (MCAO/R) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) treated bEnd.3 cells were used to evaluate the synergistic effects between edaravone and (+)-borneol. The cerebral exposure of edaravone was detected using a rapid HPLC-MS/MS method. Then, we examined whether the mechanism by which (+)-borneol increases the cerebral concentration of edaravone occurs via paracellular or transcellular pathways, and we explored potential binding targets.</div></div><div><h3>Results</h3><div>The combined administration of edaravone and (+)-borneol significantly attenuating CI/R injury both in vivo and in vitro. What captured our interest was that the co-administration of (+)-borneol increased the exposure of edaravone in cerebral infarction area. We found that the combination of (+)-borneol contributed to the maintenance of BBB integrity. The increased expressions of tight junction proteins indicated that paracellular pathway plays a limited role in the elevated cerebral edaravone concentrations. Furthermore, we found that the co-administration of (+)-borneol up-regulated the expressions of influx transporters (OAT1 and OAT3) and down-regulated the expressions of efflux transporters (P-gp and MRP1). Inhibitor experiments further confirmed that the involvement of P-gp and OAT1/3 in the transcellular transport of edaravone across BBB. Finally, we verified that (+)-borneol could directly bind to P-gp and OAT3, facilitating the entry of edaravone into brain and reducing its efflux.</div></div><div><h3>Conclusion</h3><div>This study demonstrated for the first time that (+)-borneol could enhance the concentration of edaravone in the infarcted region under conditions of CI/R. The underlying mechanisms may involve the enhancement of trans-BBB delivery of edaravone by (+)-borneol through OAT3/P-gp-mediated transcellular transport.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156521"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453138","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":"Sakuranetin ameliorates experimental colitis in a gut microbiota-dependent manner","authors":"Lian Wang ,&nbsp;Zhen Zhang ,&nbsp;Xiaohua Chen ,&nbsp;Zhiyuan Wang ,&nbsp;Xue Song ,&nbsp;Zhijun Geng ,&nbsp;Xiaofeng Zhang ,&nbsp;Yueyue Wang ,&nbsp;Jing Li ,&nbsp;Jianguo Hu ,&nbsp;Lugen Zuo","doi":"10.1016/j.phymed.2025.156540","DOIUrl":"10.1016/j.phymed.2025.156540","url":null,"abstract":"<div><h3>Background</h3><div>The progression of inflammatory bowel disease (IBD) is closely connected with intestinal flora dysbiosis. Sakuranetin (SAK) is a natural compound with anti-inflammatory and antibiosis activities. We investigated the properties and mechanisms of SAK on IBD-like colitis.</div></div><div><h3>Methods</h3><div>Mice with dextran sulfate sodium (DSS)-induced colitis were accomplished to assess the effects of SAK on colitis, as well as intestinal mucosal immune imbalance and intestinal barrier dysfunction. 16S rDNA was used to characterize the intestinal flora, and the short-chain fatty acid (SCFA) content in faeces was calculated using GS‒MS. Faecal microbiota transplantation (FMT) and a pseudosterile model (antibiotic cocktail, ABX) were used to evaluate whether the effects of SAK on colitis were dependent on the gut flora. Pathohistological and biochemical tests were used to estimate the safety of SAK.</div></div><div><h3>Results</h3><div>SAK significantly ameliorated DSS-induced colitis in mice, verified by decreased weight loss, less colon shortening, and lower disease activity, histology and colonoscopy scores. Moreover, SAK alleviated gut dysbiosis and elevated the abundance of SCFA-producing bacteria in DSS-treated mice. Meanwhile, SAK increased faecal SCFA levels and activated GPR41/43 signalling. SAK also improved Treg/Th17 homeostasis and intestinal barrier function. In addition, ABX and FMT experiments confirmed that the ability of SAK to alleviate colitis was mediated through the gut flora. Finally, a safety experiment revealed that SAK had no significant adverse effects on major organ or liver/kidney function.</div></div><div><h3>Conclusions</h3><div>SAK may improve the intestinal immune balance and barrier function by regulating intestinal flora dysbiosis and increasing SCFA production, thereby protecting against colitis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156540"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473834","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":"Effect of Qishen Yiqi dripping pills on the classification of ejection fraction in patients with ischaemic heart failure: A prospective cohort study","authors":"Zhou Zhou ,&nbsp;Shuai Wang ,&nbsp;Zixuan Fan ,&nbsp;Zeyu Zhang ,&nbsp;Xuan Zhang ,&nbsp;Zhiqiang Zhao ,&nbsp;Xianliang Wang ,&nbsp;Jingyuan Mao","doi":"10.1016/j.phymed.2025.156530","DOIUrl":"10.1016/j.phymed.2025.156530","url":null,"abstract":"<div><h3>Background</h3><div>In patients with heart failure (HF), improved left ventricular ejection fraction (LVEF) classification is closely associated with increased survival rates. However, even patients receiving guideline-directed medical therapy (GDMT) still struggle with poor cardiac function and high rates of readmission. Enhancing cardiac function in HF patients and reducing the occurrence of adverse events (AEs) remain critical challenges at present.</div></div><div><h3>Purpose</h3><div>This study was designed to evaluate the effects of the Qishen Yiqi dripping pills (QSYQ) on the EF classification of patients with ischaemic HF (IHF).</div></div><div><h3>Study design and methods</h3><div>This is a secondary analysis of data from a multicentre, prospective cohort study involving 1,225 patients with IHF from 84 centres. We selected IHF patients with reduced (HFrEF) and mildly reduced (HFmrEF) EF. One-to-one propensity score matching (PSM) was performed to compare patients who received GDMT alone (control group) with patients who received additional treatment with QSYQ (QSYQ group). The primary outcome was the longitudinal improvement in EF at 90 days, defined as a change in EF classification from HFrEF to HFmrEF/HFpEF (HF with preserved EF) or from HFmrEF to HFpEF, with an increase in EF of at least 10 %. The secondary outcome was a composite endpoint consisting of all-cause mortality, hospitalization for HF, hospitalization for unstable angina, revascularization, nonfatal stroke, and malignant arrhythmias. Additionally, the New York Heart Association (NYHA) functional classification, Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and safety were evaluated.</div></div><div><h3>Results</h3><div>Compared with the control treatment, the addition of QSYQ treatment for 90 days led to a 28 % increase in the improvement rate of EF classification in HFmEF or HFmrEF patients (RR: 1.28; 95 % CI: 1.03–1.59; <em>p</em> = 0.023), a 50 % reduction in the occurrence of composite endpoints (HR: 0.50; 95 % CI: 0.25–0.99; <em>p</em> = 0.04), a 40 % increase in the improvement rate of NYHA functional classification (RR: 1.40; 95 % CI: 1.26–1.55; <em>p</em> &lt; 0.001), and a greater reduction in MLHFQ scores (-16.00 (-7.00, -27.00) vs. -8.00 (-1.00, -17.00), <em>p</em> &lt; 0.001). Additionally, no increased risk of AEs was observed with the use of the QSYQ.</div></div><div><h3>Conclusions</h3><div>As a complementary strategy in addition to HF guideline-directed treatments, QSYQ can further improve EF classification, reduce the occurrence rate of the composite endpoint, improve quality of life, and improve the safety profile of patients with IHF. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR-ONRC-14,004,407).</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156530"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445377","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":"Anti-inflammatory effects of Rhus javanica ethanol extract for pulmonary and colonic disorders","authors":"Lei Huang ,&nbsp;Jinghan Su ,&nbsp;Yuhao Wang ,&nbsp;Canglang Mou ,&nbsp;Won Young Jang ,&nbsp;Sun Moo Rhee ,&nbsp;Long You ,&nbsp;Yerkyesh Khamit ,&nbsp;Ji Won Kim ,&nbsp;Ji Hye Yoon ,&nbsp;Ziliang He ,&nbsp;Jaeyoun Lee ,&nbsp;Seung Hyun Kim ,&nbsp;Fangfang Wang ,&nbsp;Fan Qu ,&nbsp;Youn Kyoung Son ,&nbsp;Byoung-Hee Lee ,&nbsp;Eun Sil Kim ,&nbsp;Jae Youl Cho","doi":"10.1016/j.phymed.2025.156535","DOIUrl":"10.1016/j.phymed.2025.156535","url":null,"abstract":"<div><h3>Background</h3><div><em>Rhus javanica</em> is a traditional medicinal herb widespread in East Asia, including Korea, China, and Japan. Valued for its antidiarrheal, bactericidal, and anti-inflammatory properties, it epitomizes the synergy of traditional wisdom and natural benefits.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-inflammatory properties of Rhus javanica ethanol extract (Rj-EE) in both in vitro and in vivo models, elucidate the underlying mechanisms, and provide a theoretical foundation for its potential use as a natural therapeutic option for clinical colitis and lung diseases.</div></div><div><h3>Study Design</h3><div>RAW264.7 cells, peritoneal macrophages, HEK293T cells, and mouse models of acute lung injury and acute ulcerative colitis were used to evaluate the anti-inflammatory activity of Rj-EE.</div></div><div><h3>Methods</h3><div>In this study, the phytochemical constituents of Rj-EE were identified by GC–MS and LC-MS. Inflammatory targets were sourced from GeneCards and Swiss Target Prediction databases. Gene ontology and KEGG analyses revealed Rj-EE's anti-inflammatory mechanisms. Nitric oxide (NO) production and cell viability were assessed with Griess and MTT assays, respectively. Inflammatory cytokines were measured by RT-PCR, transcription factor activity by luciferase assays, and protein expression through Western blotting. Overexpression and CETSA assays were conducted in HEK293T cells. In vivo model animals with lipopolysaccharide-induced acute lung injury and dextran sulfate sodium–induced acute ulcerative colitis were treated with Rj-EE and then assessed by RT-PCR, hematoxylin and eosin (H&amp;E), cytokine analysis via an enzyme-linked immunosorbent assay, and Western blotting.</div></div><div><h3>Results</h3><div>KEGG analysis identified the NF-κB pathway as key to Rj-EE's anti-inflammatory effects, with Src as a central target. Molecular docking showed strong binding between Rj-EE's active components and key genes. In vitro, Rj-EE reduced NO production and inflammatory mRNA markers, and inhibited MyD88- and TRIF-induced <em>NF-κB</em> and <em>AP-1</em> activity. It also targeted Src and Syk. In vivo, Rj-EE alleviated colitis and lung injury.</div></div><div><h3>Conclusion</h3><div>Overall, Our findings lay a foundation for further research into Rj-EE's molecular anti-inflammatory mechanisms and suggest that <em>Rhus javanica</em> could be explored as a potential anti-inflammatory agent targeting Src and Syk for conditions like lung injury and colitis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156535"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453176","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":"Siegesbeckia orientalis ethanol extract impedes RAGE-CD11b interaction driven by HMGB1 to alleviate neutrophil-involved neuronal injury poststroke","authors":"Jinfen Chen ,&nbsp;Xingping Quan ,&nbsp;Yiyang Li ,&nbsp;Junming Chen ,&nbsp;Jiacheng Hu ,&nbsp;Manfei Zhou ,&nbsp;Ying Chen ,&nbsp;Jiali Chen ,&nbsp;Caisheng Wu ,&nbsp;Hua Yu ,&nbsp;Yonghua Zhao","doi":"10.1016/j.phymed.2025.156541","DOIUrl":"10.1016/j.phymed.2025.156541","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Ischemic stroke is a life-threatening cerebrovascular disease with limited therapeutic options. During the progression of acute ischemic stroke (AIS), neutrophil-involved inflammation mediated by high mobility group box 1 (HMGB1) considerably contributes to intensification of neuronal injury. &lt;em&gt;Siegesbeckia orientalis&lt;/em&gt; L. (SO), one of the primary sources of Sigesbeckiae Herba, is promising in anti-neuroinflammation and neutrophil function modulation. Consequently, it is supposed that SO could fight against neuronal inflammatory injury following AIS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The current study struggles to explore the ameliorative effects of ethanol extract of SO (EESO) on neuronal inflammatory injury following AIS, and dissect the related mechanisms focusing on HMGB1-driven neutrophil recruitment and neutrophil extracellular traps (NETs) generation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Murine photothrombotic stroke model was established to evaluate the ameliorative effects of EESO administration against AIS. Histopathological examination and immunofluorescence staining were conducted for the observation of cerebral neuronal injury, neutrophil infiltration and NETs generation. Additionally, inflammatory indexes and serum HMGB1 levels were also detected through qPCR and ELISA, respectively. &lt;em&gt;In vitro&lt;/em&gt;, the effects of EESO-containing serum administration on neutrophil migration and NETs generation were also assessed. HMGB1-overexpressed mimic transfection, cellular thermal shift assay and coimmunoprecipitation were employed to investigate whether the compounds from EESO-containing serum targeted HMGB1 to block the receptor for advanced glycation end products (RAGE)-CD11b interaction. Furthermore, potential active compounds of EESO targeting HMGB1 were screened and verified.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;EESO administration alleviated photochemically induced murine AIS as revealed by remarkably reducing infract volume as well as improving cerebral blood flow and neurological functions. Moreover, EESO administration prominently mitigated secondary neuronal injury, restrained neutrophil infiltration and NETs generation, as well as lowered the levels of serum pro-inflammatory mediators and HMGB1. &lt;em&gt;In vitro&lt;/em&gt;, the compounds in EESO-containing serum directly interacted with neuron-derived HMGB1. HMGB1-driven neutrophil migration and NETs generation through the RAGE-CD11b interaction were also reversed by EESO-containing serum administration. Additionally, isoimperatorin, 4,7-dimethyltetral-1-one, perillartine and darutigenol, as the active components, contributed to the suppressive effects of EESO on neutrophil migration and NETs generation driven by HMGB1.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In the present study, it was demonstrated that HMGB1 promoted interaction between CD11b and RAGE to drive NETs generation for the first time. Furthermore, EESO was proved to target neuron-derived H","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156541"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453175","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":"Tianqi Yizhi Granule alleviates cognitive dysfunction and neurodegeneration in SAMP8 mice via the PKC/ERK pathway","authors":"Yi Zeng ,&nbsp;Sixia Yang ,&nbsp;Zeping Xie ,&nbsp;Qitian Li ,&nbsp;Yuhua Wang ,&nbsp;Qiaowu Xiong ,&nbsp;Xiaotong Liang ,&nbsp;Hui Lu ,&nbsp;Weidong Cheng","doi":"10.1016/j.phymed.2025.156542","DOIUrl":"10.1016/j.phymed.2025.156542","url":null,"abstract":"<div><h3>Background</h3><div>Given the lack of satisfactory clinical treatments for Alzheimer's disease (AD), a neurodegenerative condition detrimental to health, developing alternative therapies is critical. Tianqi Yizhi Granule (TQYZ) is a preparation used to treat AD based on traditional Chinese medicine theory, the latent mechanisms of which await elucidation.</div></div><div><h3>Purpose</h3><div>This study sought to investigate the neuroprotective properties of TQYZ while exploring its potential therapeutic mechanisms using network pharmacology analyses and experimental validation.</div></div><div><h3>Methods</h3><div>Network pharmacology analyses were performed. Cognitive and neurodegenerative alterations were evaluated through behavioral tests and histological staining. For in vivo and in vitro experiments, short hairpin RNA sequences were transfected via adeno-associated virus vectors to verify the predicted mechanism.</div></div><div><h3>Results</h3><div>A total of 159 potential therapeutic targets of TQYZ overlapped with AD-related targets. In senescence-accelerated mouse prone 8 (SAMP8) mice, treatment with TQYZ significantly improved cognitive function, ameliorated neuronal damage and apoptosis, and upregulated the protein expression of PKC/ERK pathway members. TQYZ maintained the mitochondrial membrane potential, reduced the generation of reactive oxygen species, and inhibited neuronal apoptosis in Aβ_25–35-induced HT22 cells. However, these neuroprotective effects were notably reduced in shRNA PRKCB-transfected HT22 cells and SAMP8 mice.</div></div><div><h3>Conclusions</h3><div>TQYZ mitigates the pathological degeneration process and cognitive impairment in SAMP8 mice and suppresses mitochondrial dysfunction and apoptosis in HT22 cells treated with Aβ_25–35. Its neuroprotective mechanism is linked to PKC/ERK pathway activation. This study highlights a promising strategy for AD therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156542"},"PeriodicalIF":6.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463632","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}