Phytomedicine最新文献

{"title":"Higenamine protects against doxorubicin-induced heart failure by attenuating ferroptosis via modulating the Nrf2/GPX4 signaling pathway","authors":"Jianxia Wen ,&nbsp;Lu Li ,&nbsp;Dinglin Ou ,&nbsp;Jianling Li ,&nbsp;Yi Yang ,&nbsp;Liting Duan ,&nbsp;Xinghai Zhang ,&nbsp;Yichan Zhu ,&nbsp;Junjie Hao ,&nbsp;Yuling Tong","doi":"10.1016/j.phymed.2025.156670","DOIUrl":"10.1016/j.phymed.2025.156670","url":null,"abstract":"<div><h3>Background</h3><div>Higenamine (HG), a benzylisoquinoline alkaloid in <em>Aconiti Lateralis Radix Praeparata</em> (ALRP), has cardioprotective effects. Prior research indicated its potential anti-heart failure (HF) function, yet the molecular mechanism remained elusive.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the underlying mechanism of HG against doxorubicin (DOX)-induced HF <em>via</em> an integrated approach involving gut microbiota, untargeted metabolomics, network pharmacology, and molecular biology.</div></div><div><h3>Methods</h3><div>DOX was employed to induce HF in rats and H9c2 cardiomyocytes injury models. Cardiac injury was assessed using hemodynamic indices, cardiac injury biomarkers, and oxidative stress markers. Cell counting kit-8 (CCK-8) method and high-content analysis were used to investigate the effects of HG on the cell proliferation, morphology and mitochondrial function of H9c2 cardiomyocytes. 16S rDNA sequencing analysis, untargeted metabolomics, and network pharmacology were performed to identify the multi-target and multi-pathway mechanisms of HG in treating HF. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western Blotting was used to investigate its intervention on the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) ferroptosis pathway.</div></div><div><h3>Results</h3><div>HG alleviated DOX-mediated myocardial injury by enhancing cardiac and mitochondrial function, reducing oxidative stress levels, and promoting cell proliferation. Effects of HG on changes in the gut microbiota of rats is characterized by a low abundance of <em>Firmicutes</em> and <em>Proteobacteria</em>, along with a high abundance of <em>Bacteroidetes</em> and <em>Actinobacteria</em>, indicating an improvement in DOX-induced dysbiosis. Untargeted metabolomics combined with network pharmacology showed that HG exerted anti-HF effects by regulating eight metabolites, eight pathways, and interacting with ferroptosis-related targets. Molecular biology studies revealed its cardioprotective effects <em>via</em> regulating the Nrf2/GPX4 ferroptosis pathway.</div></div><div><h3>Conclusion</h3><div>HG could inhibit ferroptosis and protect against HF by regulating the Nrf2/GPX4-mediated \"mitochondrial-ferroptosis\" pathway, offering a potential treatment strategy for HF.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156670"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817283","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 “B. glomerulata promotes neuroprotection against ischemic stroke by inhibiting apoptosis through the activation of PI3K/AKT/mTOR pathway” [Phytomedicine, 2024, 132:155817]","authors":"","doi":"10.1016/j.phymed.2025.156636","DOIUrl":"10.1016/j.phymed.2025.156636","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156636"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711070","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":"Validated herbal extracts for alleviating chemotherapy-induced myelosuppression: A systematic review and meta-analysis","authors":"De-Hui Wang,&nbsp;Xiao-Ni Ma,&nbsp;Yan Wang,&nbsp;Yi-Xiao Wei,&nbsp;Po Hu,&nbsp;Yang Pan","doi":"10.1016/j.phymed.2025.156659","DOIUrl":"10.1016/j.phymed.2025.156659","url":null,"abstract":"<div><h3>Background</h3><div>Myelosuppression is a major side effect of chemotherapy. It impairs hematopoietic function of bone marrow, decreases immunity, increases uncontrolled bleeding. Advanced myelosuppression even forces discontinuation of treatment. The agents that reduce myelosuppression can promote outcomes of clinical chemotherapy, and herbal extracts show the effects.</div></div><div><h3>Purpose</h3><div>This study aims to evaluate the effects of herbal extracts on chemotherapy-induced myelosuppression, providing evidence of their potential in mitigating myelosuppression and exploring their prospects for further clinical application.</div></div><div><h3>Methods</h3><div>We conducted a systematic search in six English and Chinese databases and screened studies that met the inclusion criteria. Through a systematic review of animal experiments, data were extracted and analyzed from studies that evaluated the effect of herbal extracts on myelosuppression, provided appropriate control groups for comparison, and reported key outcomes related to myelosuppression. We screened 6169 articles and ultimately selected 95 experimental studies for final analysis.</div></div><div><h3>Results</h3><div>The comprehensive analysis indicates that herbal extracts have a significant protective effect on myelosuppression. Herbal extracts treatment increases levels of hemoglobin, white blood cells, platelets, and granulocytes, while also enhancing immunity, which may be an effective way to alleviate chemotherapy-induced myelosuppression.</div></div><div><h3>Conclusion</h3><div>This systematic review and meta-analysis underscore the significant role of herbal extracts in alleviating chemotherapy-induced myelosuppression, laying a foundation for future clinical.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156659"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816792","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":"Schisandrin B regulates mitochondrial dynamics via AKT1 activation and mitochondrial targeting to ameliorate renal ischemia-reperfusion injury","authors":"Changhong Xu ,&nbsp;HuaBin Wang ,&nbsp;Hailong Wang ,&nbsp;Jiangwei Man ,&nbsp;Yun Deng ,&nbsp;Yi Li ,&nbsp;Kun Cheng ,&nbsp;Jiping Niu ,&nbsp;Huiming Gui ,&nbsp;Shengjun Fu ,&nbsp;Li Yang","doi":"10.1016/j.phymed.2025.156672","DOIUrl":"10.1016/j.phymed.2025.156672","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Renal ischemia-reperfusion injury (RIRI) is a significant cause of acute kidney injury(AKI) and delayed graft function(DGF), impacting post-transplant outcomes. Mitochondrial dynamics, in particular fission and fusion, play a pivotal role in the cellular response to RIRI. The modulation of these dynamics represents a potential therapeutic target. Schisandrin B (Sch B), a component derived from traditional Chinese medicine, has shown protective roles in various organ injuries, but its effect on RIRI through mitochondrial dynamics remains unexplored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study explores the previously uninvestigated role of Sch B in modulating mitochondrial dynamics as a potential means of alleviating RIRI. By focusing on mitochondrial fission and fusion, this research provides novel insights into the therapeutic potential of Sch B, distinguishing it from existing approaches.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;HK-2 cells were treated with hypoxia/reoxygenation (HR) in order to simulate renal ischemia-reperfusion injury (RIRI) in vitro. In vivo, mice underwent renal ischemia followed by reperfusion, which allowed for the simulation of the injury. Sch B's impact on mitochondrial dynamics, apoptosis, and oxidative stress was assessed through mitochondrial morphology assays, Western blotting for mitochondrial and apoptotic markers, TUNEL staining, and measurement of reactive oxygen species. Key molecular interactions were explored via Western blotting, molecular docking, SPR, and cellular thermal shift assays. In vivo, renal pathological damage was evaluated using HE, PAS, and TUNEL staining, while immunohistochemistry and immunofluorescence were employed to detect the expression levels of mitochondrial dynamics proteins and p-AKT1.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;First, we unveiled that Schisandrin B (Sch B) significantly mitigated oxidative stress and apoptosis in HK-2 cells subjected to hypoxia-reoxygenation conditions. Sch B pretreatment notably enhanced cell viability and mitochondrial function, demonstrating its superior antioxidant capabilities compared to NAC. Second, we discovered that Sch B's protective effects involve regulating mitochondrial dynamics by decreasing fission markers, such as DRP1, while increasing fusion proteins, including OPA1 and MFN2. Furthermore, our studies revealed that Sch B directly binds to AKT1, promoting its phosphorylation and localization to mitochondria, thereby enhancing mitochondrial resilience. Finally, we demonstrated that in vivo administration of Sch B reduced renal damage and apoptosis in mouse models of renal ischemia-reperfusion injury (RIRI), while immunohistochemical analyses unveiled its role in promoting mitochondrial fusion and reducing fission, marking a significant advancement in understanding Sch B's therapeutic potential in RIRI.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings demonstrate for the first time that Sch B directly inter","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156672"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823335","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":"Stevia rebaudiana root polysaccharide modulates liver metabolism, bile acid, and gut microbiota improving HFD-induced NAFLD: Potential roles of ACSL1 and FADS2","authors":"Yulong Bao ,&nbsp;Xiaolong Shang ,&nbsp;Guangdong Hu ,&nbsp;Jiapeng Wang ,&nbsp;Chunyan Liu ,&nbsp;Qiuyue Lv ,&nbsp;Hui Che ,&nbsp;Jun Han ,&nbsp;Taili Shao ,&nbsp;Guodong Wang","doi":"10.1016/j.phymed.2025.156680","DOIUrl":"10.1016/j.phymed.2025.156680","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder characterized by liver lipid accumulation and insulin resistance. However, effective therapeutic drugs for NAFLD are currently unavailable. <em>Stevia rebaudiana</em> root polysaccharides (SRRP) are inulin-type polysaccharides known for their hypoglycemic properties. Despite this, the effects of SRRP on improving NAFLD and the underlying mechanisms remain poorly understood.</div></div><div><h3>Purpose</h3><div>This study aims to evaluate the potential of SRRP in alleviating NAFLD and to explore its mechanisms of action.</div></div><div><h3>Methods</h3><div>NAFLD was induced in male C57BL/6 J mice through high-fat diet (HFD) feeding, with subsequent SRRP administration over 8 weeks. Comprehensive assessments included serum biochemical profiling, hepatic histopathological examination, and proinflammatory enzyme activity quantification. Mechanistic investigations employed tripartite analytical approaches: gut microbiota analysis via 16S rRNA sequencing, hepatic metabolomic profiling and bile acid profiling, and validation of transport protein expression through Western blot (WB) techniques.</div></div><div><h3>Results</h3><div>SRRP administration significantly alleviated NAFLD through reduced serum lipid concentrations, ameliorated inflammatory responses and oxidative stress, and decreased hepatic lipid deposition mechanistically, SRRP improved the structure of the gut microbiota by enhancing the proliferation of beneficial bacterial, including <em>Lactobacillales</em> and <em>Bifidobacteriales</em>, which subsequently elevated circulating Cholic acid (CA) and Chenodeoxycholic acid (CDCA), and improved hepatic lipid metabolites. Notably, KEGG from metabolomics indicated that the linoleic acid pathway might be associated with the improvement in hepatic lipid metabolite levels by SRRP. In Western blot analysis, SRRP significantly upregulated hepatic ACSL1 and FADS2 in NAFLD mice, demonstrating that the alleviation of NAFLD by SRRP may be achieved through the reduction of hepatic lipid accumulation.</div></div><div><h3>Conclusions</h3><div>SRRP exerts effects on improving NAFLD by modulating the gut microbiota, hepatic metabolites, bile acid levels, and the expression of ACSL1 and FADS2 proteins, providing more scientific evidence and support for the improvement of NAFLD by SRRP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156680"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816890","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":"New insights into phytochemicals via protein glycosylation focused on aging and diabetes","authors":"Yihan Chen ,&nbsp;Suyue Lu ,&nbsp;Shuo Shan ,&nbsp;Weihao Wu ,&nbsp;Xinxin He ,&nbsp;Mohamed A. Farag ,&nbsp;Weichao Chen ,&nbsp;Chao Zhao","doi":"10.1016/j.phymed.2025.156673","DOIUrl":"10.1016/j.phymed.2025.156673","url":null,"abstract":"<div><h3>Background</h3><div>Protein glycosylation as a common post-translational modification that has significant impacts on protein folding, enzymatic activity, and interfering with receptor functioning. In recent years, with the rapid development of glycopeptide enrichment and analysis technology and the deepening of glycosylation research, glycosylation has gradually become a sign of disease occurrence and development. Multiple investigations suggest that protein glycosylation affect the advances of diabetes and aging.</div></div><div><h3>Purpose and Methods</h3><div>This review was focused on the action mechanisms of glycosylated proteins production, permanent abnormalities in extracellular matrix component function, inflammatory and reactive oxygen species production, as well as the glycosylated characterizations of diabetes and aging. Further, advances in glycosylation analysis and detection methods are presented for the first time, highlighting for needed future developments. All literatures were gathered from PubMed and Google Scholar.</div></div><div><h3>Results</h3><div>Herein, we review how protein glycosylation impacts the progression of diabetes and aging. Specifically, we focus on various types of glycosylation, including N-linked glycosylation, O-linked glycosylation, C-glycosylation, S-glycosylation, and glycophosphatidylinositol (GPI) anchors. N-linked glycosylation and O-linked glycosylation are commonly observed glycosylation forms, wherein O-GlcNAcylation plays a significant role in diabetes, while N-glycan could serve as biomarkers for identifying inflammation and aging.</div></div><div><h3>Conclusions</h3><div>Protein glycosylation produces a vastly larger number of core glycan structures through utilizing at least 173 glycosyltransferases and repeated common scaffolds. Single protein may contain multiple glycosylation sites, and the structure and occupancy of glycan at each site may be different, resulting in the macro heterogeneity of protein glycosylation. This review will contribute to how protein glycosylation impacts the life progress of cells and its association with diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156673"},"PeriodicalIF":6.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817303","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":"Anemarchalconyn, a natural alkyne ketone compound, inhibits HCC cell growth by suppressing Polθ and inducing synthetic lethality in Homologous recombination deficiency cells","authors":"Junnan Li ,&nbsp;Wenwen Deng ,&nbsp;Tianjie Zhou ,&nbsp;Xinyang Zhang ,&nbsp;Liqing Hu ,&nbsp;Shasha Fan ,&nbsp;Hui Zou","doi":"10.1016/j.phymed.2025.156679","DOIUrl":"10.1016/j.phymed.2025.156679","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with limited treatment options. Dysfunction of DNA damage response (DDR) genes, including Polθ and BRCA1, is implicated in HCC development and progression, offering novel therapeutic targets.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the anticancer effects of anemarchalconyn (SL-001) on HCC and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We leveraged The Cancer Genome Atlas (TCGA) data analysis to explore the potential of POLQ/BRCA1 as therapeutic targets in liver cancer, as well as their association with the prognostic clinicopathological features of hepatocellular carcinoma (LIHC). We have isolated SL-001 and then developed an innovative and efficient synthesis strategy for SL-001, a natural alkyne ketone compound isolated from <em>Selaginella tamariscina,</em> and assessed the anti-tumor effects of SL-001 through in vitro and in vivo studies.</div></div><div><h3>Results</h3><div>TCGA analysis revealed significant upregulation of POLQ and BRCA1 in HCC tumors compared to normal tissues. Additionally, POLQ and BRCA1 expression demonstrated high accuracy in distinguishing tumor tissues and correlating with reduced overall survival. SL-001 exhibited robust anti-proliferative effects on hepatocellular carcinoma (HCC) cells, surpassing the efficacy of the current standard treatment, sorafenib. The anti-HCC effect of SL-001 was associated with downregulation of POLQ, a key protein involved in alternative DNA repair pathways. Importantly, SL-001 demonstrated enhanced inhibitory effects on Homologous recombination deficiency (HRD) HCC cells, suggesting a synthetic lethal interaction between SL-001 and HRD.</div></div><div><h3>Conclusion</h3><div>SL-001 represents a promising therapeutic candidate for HCC, particularly for patients with HRD tumors. Its mechanism involves inhibiting POLQ and disrupting DNA repair pathways, leading to increased DNA damage and cell death in HRD cells. This study provides a foundation for further investigation of SL-001 as a targeted therapy for HCC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156679"},"PeriodicalIF":6.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817429","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":"Discovery of the pharmacodynamic material basis of Danggui Buxue Decoction in the treatment of diabetic kidney disease based on lipidomics regulation","authors":"Xu Wang ,&nbsp;Jing Liu ,&nbsp;Tingting Liu ,&nbsp;Cheng Fang ,&nbsp;Lin Ding ,&nbsp;Qiyao Li ,&nbsp;Kaidi Yang ,&nbsp;Xiuhong Wu","doi":"10.1016/j.phymed.2025.156643","DOIUrl":"10.1016/j.phymed.2025.156643","url":null,"abstract":"<div><h3>Background</h3><div>Danggui Buxue Decoction (DBD) is a formula used for treating diabetic kidney disease (DKD). However, the pharmacodynamic material basis of DBD in DKD therapy remains unclear, hindering its industrial development and innovation in drug formulations.</div></div><div><h3>Purpose</h3><div>Lipid metabolism disorder is a key pathological mechanism in DKD progression. This study employs lipidomics to elucidate and validate the pharmacodynamic material basis of DBD in treating DKD.</div></div><div><h3>Methods</h3><div>Forty-eight male SD rats were used in the experiment, with 8 rats per group. The DKD model was constructed with a diet high in fat and sugar, together with intraperitoneal administration of low-dose STZ and unilateral nephrectomy. DBD was administered continuously for 10 weeks to assess its therapeutic efficacy on DKD. Lipid biomarkers in the DKD models were analyzed using lipidomics, while the transitional components in the blood of DBD-treated rats were characterized through UPLC-QE-Orbitrap MS. Potential pharmacodynamic substances were identified by correlating lipid biomarkers with active ingredients in vivo, followed by molecular docking and in vitro experiments to validate key pharmacodynamic components.</div></div><div><h3>Results</h3><div>DBD significantly improved blood glucose, blood lipid levels, and renal function in DKD model rats. Lipidomics identified 37 lipid biomarkers in the DKD models, and DBD demonstrated a marked corrective effect on these biomarkers. In the therapeutically effective state, 91 blood transitional components of DBD were identified. Correlation analysis revealed 44 pharmacodynamic substances associated with DKD treatment, with ferulic acid, calycosin, astragaloside IV, and ligustilide being the key components. These substances acted by increasing the levels of SIRT1, PPARG, and ABCA1 proteins in lipid-deposited podocytes.</div></div><div><h3>Conclusion</h3><div>In conclusion, this study explained the scientific connotation of DBD treatment of DKD with modern scientific language from three aspects: pharmacodynamic evaluation, pharmacodynamic material basis and mechanism of action from the perspective of lipid metabolism balance for the first time, and provided an empirical basis for the modern application of traditional Chinese medicinal prescriptions.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156643"},"PeriodicalIF":6.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816889","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":"Mechanistic insights into the potentiation and toxicity mitigation of myocardial infarction treatment with salvianolate and ticagrelor","authors":"Yan Wan ,&nbsp;Ming-Hao Yuan ,&nbsp;Xue Liang ,&nbsp;Yu-Lu Wang ,&nbsp;Qiang Ye ,&nbsp;Cheng Peng ,&nbsp;Yi-Ping Guo ,&nbsp;Li Guo","doi":"10.1016/j.phymed.2025.156676","DOIUrl":"10.1016/j.phymed.2025.156676","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Ticagrelor (TG), a first-line treatment for myocardial infarction (MI), is limited in its clinical application due to the risk of elevated uric acid (UA) levels. Salvianolate injection (SAL), an adjunctive therapy for MI, has been reported to have potential for UA reduction. Although the combined use of TG and SAL has been reported in clinical practice, no studies have focused on the optimal ratio for the combination or the mechanisms underlying their synergistic effects on MI and UA reduction.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study follows the principle of enhancing efficacy and reducing toxicity through combination therapy. It aims to explore the optimal combination ratio (low-dose combination group: 10 mg/kg TG + 10 mg/kg SAL; medium-dose combination group: 10 mg/kg TG + 20 mg/kg SAL; high-dose combination group: 20 mg/kg TG + 20 mg/kg SAL) by evaluating both UA-lowering and anti-MI activities. Additionally, the study investigates the underlying mechanisms of anti-hyperuricemia and anti-MI through metabolomics and transcriptomics, in hopes of providing insights into rational clinical use of these drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Kidney H&amp;E staining, biochemical assays (UA, BUN, XOD, CRE), in vitro XOD detection, UA transporter protein analysis (GLUT9, OAT1, ABCG2, URAT1), and bioinformatics (PI3K/AKT) were used to assess anti-hyperuricemic activity under different combination ratios. ECG, echocardiography, biochemical assays (CK, LDH), ELISA (cTnT), and H&amp;E staining were employed to evaluate anti-MI activity. The optimal combination ratio was determined based on both anti-hyperuricemic and anti-MI effects, and metabolomics and transcriptomics were used to explore the mechanisms of anti-hyperuricemia and anti-MI for this ratio.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The TG-SAL combination reduced TG-induced hyperuricemia by enhancing renal function, UA excretion, and PI3K-AKT expression, as well as inhibiting UA reabsorption and production. Simultaneously, the combination alleviated cardiac injury and restored abnormal cardiac function, demonstrating anti-MI activity. Among the groups, the medium-dose combination showed the best synergistic effect. Further, metabolomics indicated that the anti-hyperuricemic mechanism of the medium-dose combination was related to the positive regulation of selenium compound metabolic pathways. Transcriptomics revealed that the anti-MI activity of the medium-dose combination was associated with the inhibition of cardiac muscle contraction pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The TG-SAL combination exhibited ideal synergistic effects in enhancing anti-MI activity and reducing TG-induced hyperuricemia, with the medium-dose combination demonstrating the best results. Mechanistically, the medium-dose combination exerted anti-hyperuricemic effects by positively regulating selenium compound metabolic pathways and anti-MI activity by inhibiting cardia","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156676"},"PeriodicalIF":6.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817281","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":"Erianin alleviates doxorubicin-induced cardiotoxicity by activating the Keap1-Nrf2 signaling pathway","authors":"Shiyao Kang ,&nbsp;Huimin Li ,&nbsp;Ming Li ,&nbsp;Yuan Zhao ,&nbsp;Jianyu Pang ,&nbsp;Juhua Dan ,&nbsp;Miaomiao Sheng","doi":"10.1016/j.phymed.2025.156684","DOIUrl":"10.1016/j.phymed.2025.156684","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX) has significant toxic side effects on cardiomyocytes, and existing preventive drug dexrazoxane has serious side effects. Therefore, in-depth research on drugs that can enhance the antitumor effect of DOX and simultaneously reduce its cardiotoxicity is of crucial significance. Our study explored the regulatory role of Erianin in DOX-induced cardiotoxicity and the specific molecular mechanism.</div></div><div><h3>Methods</h3><div>In this study, we constructed a myocardial injury model in mice with DOX. The toxic side effects of DOX on the organism were determined by recording the weight changes of the mice and calculating the spleen index and heart-tibia ratio of the mice. The degree of myocardial injury in mice was evaluated by methods such as echocardiography and Sirius red staining. Further <em>in vivo</em> experiments were conducted to verify whether the silencing of Nrf2 could block the protective effect of Erianin on myocardial cells.</div></div><div><h3>Results</h3><div>We found Erianin significantly alleviated DOX-induced cardiomyocyte injury (<em>p</em> &lt; 0.0001), increased heart tissue pumping efficiency and contractility (<em>p</em> &lt; 0.001), and reduced myocardial cell fibrosis. Mechanism study showed that Erianin can bind to Keap1, promote its ubiquitination and autophagic degradation, increase the acetylation of lysine 599 site in Nrf2 protein, and activate the antioxidant stress response.</div></div><div><h3>Conclusions</h3><div>Taken together, our study had for the first time elucidated the molecular mechanism by which Erianin alleviated DOX-induced myocardial injury by activating the Keap1-Nrf2 signaling pathway. It provides a theoretical basis for the development of Erianin as a potential protective drug for DOX-induced cardiotoxicity. It has very important clinical application and translational value.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156684"},"PeriodicalIF":6.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817282","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}