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The exploration of the effect and mechanism of Shengxian decoction inhibiting acute high-altitude myocardial injury 生仙汤抑制急性高原心肌损伤的作用及机制探讨
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-26 DOI: 10.1016/j.phymed.2025.156896
Zhihan Chen , Lingyuan Zhong , Mengsong Liu , Peiwen Ding , Nan Jia , Qian Chen , Junling Liu , Yitong Wang , Jianyuan Tang
{"title":"The exploration of the effect and mechanism of Shengxian decoction inhibiting acute high-altitude myocardial injury","authors":"Zhihan Chen ,&nbsp;Lingyuan Zhong ,&nbsp;Mengsong Liu ,&nbsp;Peiwen Ding ,&nbsp;Nan Jia ,&nbsp;Qian Chen ,&nbsp;Junling Liu ,&nbsp;Yitong Wang ,&nbsp;Jianyuan Tang","doi":"10.1016/j.phymed.2025.156896","DOIUrl":"10.1016/j.phymed.2025.156896","url":null,"abstract":"<div><h3>Background</h3><div>The heart is the most vulnerable organ to acute hypobaric hypoxia exposure, acute high-altitude myocardial injury (AHMI) typically occurs in individuals who rapidly ascend from lowland areas to high-altitude regions. Effective intervention strategies for AHMI have garnered significant attention, with Shengxian decoction (SXD) emerging as a potential therapeutic agent; however, the underlying mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>The objective of this study was to explore the effective components, potential targets and regulatory mechanisms of SXD in improving AHMI.</div></div><div><h3>Study design</h3><div>This study innovatively employed the combined strategy including network pharmacology, transcriptomics, proteomics, molecular docking, and molecular biology to analyze the targets and mechanism pathways of SXD for improving AHMI. Ultra-high-performance liquid chromatography/Q Exactive HFX mass spectrometry (UHPLC-QE-MS) and network pharmacology were adopted to identify active ingredients and analyze their functions. On this basis, transcriptomics and proteomics technologies were integrated to further investigate and validate the mechanisms at both gene and protein levels. Additionally, a herbs-components-targets-pathways (HCTP) network was generated for exploration and analysis. Molecular docking was utilized for an in-depth examination of the binding activity between screened components and targets. Finally, molecular biology techniques were applied to re-confirm the targets and mechanisms involved.</div></div><div><h3>Results</h3><div>SXD effectively reduced heart’s abnormal electrical activity, inhibited the release of various myocardial enzymes, troponins and inflammatory factors into the blood. Network pharmacology, transcriptomics, proteomics revealed that inflammatory response was important for the effects of SXD in AHMI. The combined analysis of network pharmacology, transcriptomics, proteomics constructed the HCTP network encompassing 5 herbs, 13 active ingredients, 146 targets and 20 signaling pathways to elucidate the mechanism by which SXD exerts its effects on AHMI, further analysis suggested that SXD regulated IL-17, MAPK/ERK, and Ras signaling pathways to alleviate AHMI.</div></div><div><h3>Conclusion</h3><div>The positive effect of SXD on AHMI was achieved through the regulation of inflammation-related pathways (IL-17, MAPK/ERK, and Ras signaling pathways), the inhibition of inflammatory factors releases and the modulation of the inflammatory response.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156896"},"PeriodicalIF":6.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178125","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}
引用次数: 0
Mechanism of Dihydroartemisinin in activating macrophages to enhance host resistance to malaria 双氢青蒿素激活巨噬细胞增强宿主疟疾抗性的机制
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-26 DOI: 10.1016/j.phymed.2025.156913
Xin Li , Qilong Li , Ning Jiang , Kexin Zheng , Yiwei Zhang , Xiaoyu Sang , Ying Feng , Ran Chen , Qijun Chen
{"title":"Mechanism of Dihydroartemisinin in activating macrophages to enhance host resistance to malaria","authors":"Xin Li ,&nbsp;Qilong Li ,&nbsp;Ning Jiang ,&nbsp;Kexin Zheng ,&nbsp;Yiwei Zhang ,&nbsp;Xiaoyu Sang ,&nbsp;Ying Feng ,&nbsp;Ran Chen ,&nbsp;Qijun Chen","doi":"10.1016/j.phymed.2025.156913","DOIUrl":"10.1016/j.phymed.2025.156913","url":null,"abstract":"<div><h3>Background</h3><div>The property of dihydroartemisinin (DHA) in promoting host immunohomeostasis, apart from its potent antimalarial activity, has been well-recognized. However, the mechanism of DHA in activating macrophages to enhance host resistance to malaria remains unexplored.</div></div><div><h3>Purpose</h3><div>This study investigated the molecular mechanism by which DHA promotes the polarization of macrophages toward the M1 phenotype during the treatment of malaria.</div></div><div><h3>Methods</h3><div>The mouse macrophage cell line RAW 264.7 or the macrophages isolated from mice were stimulated with <em>Plasmodium berghei</em> ANKA infected red blood cells (iRBC) in the presence of DHA. The macrophage phenotypes in both <em>in vivo</em> and <em>in vitro</em> were determined using cytometric bead array and flow cytometry. To dissect the molecular mechanisms underlying macrophage responses to DHA, we initially profiled the expression of 90 genes associated with innate immunity, including the entire NLR family, in macrophages stimulated with DHA. This targeted screen strikingly revealed that only <em>Nlrp12</em> was significantly upregulated among all tested NLR genes. The function of <em>Nlrp12</em> was further dissected by <em>Nlrp12</em> knockdown in macrophages with recombinant lentiviruses encoding <em>Nlrp12</em>-specific shRNA, within the context of DHA treatment. To comprehensively define the molecular consequences of <em>Nlrp12</em> deficiency, we performed an integrated analysis by combining single-cell RNA sequencing with label-free quantitative proteomic profiling. This allowed us to systematically characterize the complex transcriptomic and proteomic dynamics in DHA-treated macrophages upon <em>Nlrp12</em> deletion.</div></div><div><h3>Results</h3><div>DHA induced macrophage polarization to M1 phenotype and enhanced phagocytosis by up-regulating the expression of NLRP12. <em>Nlrp12</em>-knockdown in macrophages reduced the expression of M1 type-associated genes, resulting in a significantly increased expression of the translocator protein (TSPO), which suppressed the secretion of inflammation-associated cytokines and blunting macrophage M1 polarization. The results of single cell RNA sequencing further revealed that DHA promoted the conversion of classical M1 macrophages into lipocalin-2 (Lcn2) <sup>high</sup> M1 macrophages.</div></div><div><h3>Conclusion</h3><div>The activation of <em>NLRP12</em> induced by DHA is crucial for M1 macrophage polarization, which plays a significant role in the clearance of <em>Plasmodium</em> parasites.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156913"},"PeriodicalIF":6.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185593","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}
引用次数: 0
UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Qishen Huanwu capsule attenuates anthracycline-induced cardiotoxicity 以UPLC-Q-TOF-MS为基础研究芪参还五胶囊减轻蒽环类药物心脏毒性的活性成分及其分子机制
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-26 DOI: 10.1016/j.phymed.2025.156877
Jin-Meng Lv , Li-Xin Wang , Jing Yang , Jing-Jing Dong , Na-Na Feng , Hong-Gui Liu , Na Zhao , Guang-Li Yin , Feng Wang
{"title":"UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Qishen Huanwu capsule attenuates anthracycline-induced cardiotoxicity","authors":"Jin-Meng Lv ,&nbsp;Li-Xin Wang ,&nbsp;Jing Yang ,&nbsp;Jing-Jing Dong ,&nbsp;Na-Na Feng ,&nbsp;Hong-Gui Liu ,&nbsp;Na Zhao ,&nbsp;Guang-Li Yin ,&nbsp;Feng Wang","doi":"10.1016/j.phymed.2025.156877","DOIUrl":"10.1016/j.phymed.2025.156877","url":null,"abstract":"<div><h3>Background</h3><div>Cardiotoxicity is a prevalent side effect linked to anthracyclines, a class of chemotherapy drugs, that frequently leads to the discontinuation of anthracycline-based treatments among cancer patients. Thus, there is a pressing need to mitigate and prevent these cardiotoxic effects. Mounting evidence suggests that Traditional Chinese Medicine may alleviate the toxic side effects of chemotherapy agents. For this reason, this study seeked to comprehensively assess the cardioprotective properties of the Qishen Huanwu capsule (QSHWC) against pirarubicin (THP)-induced cardiotoxicity in rat models and explore the underlying mechanisms.</div></div><div><h3>Methods</h3><div>The effects of QSHWC on anthracycline-induced myocyte damage was evaluated via CCK8 assay. Investigations conducted subsequently principally comprised network pharmacology methodology, Ultra-performance liquid chromatograph-hybrid quadrupole orbitrap high resolution mass spectrometer (UHPLC-Q-Orbitrap HRMS) and an anthracycline-induced cardiotoxicity (AIC) rat model to dig into the chemical constituents and potential therapeutic mechanisms of the QSHWC.</div></div><div><h3>Results</h3><div>As evidently demonstrated by in-vitro studies, QSHWC not only effectively elevated the cell viability of H9c2 after anthracycline injury, but also downregulates NLRP3 expression and LDH release. As illustrated by in-vivo studies, medium and high doses of QSHWC improved the cardiac injury caused by pirarubicin, decreased myocardial injury scores, cTnT and NT-proBNP levels, and elevated the left ventricular ejection fraction (LVEF %). By conducting HPLC-Q-Exactive-MS analysis, we identified the major parts of the QSHWC. As suggested by network pharmacology and molecular docking analyses, QSHWC may exert cardioprotective protective effects by regulating multiple signaling pathways such as PI3K/AKT and NOD-like receptors. Last but not least, animal experiments confirmed that QSHWC can up-regulate phosphorylated PI3K and phosphorylated AKT in rat myocardial tissue, while down-regulating NLRP3 levels.</div></div><div><h3>Conclusion</h3><div>QSHWC alleviates anthracycline-induced cardiotoxicity by targeting cardiac pyroptosis through the PI3K/AKT pathway, while providing a multi-target therapeutic strategy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156877"},"PeriodicalIF":6.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177910","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}
引用次数: 0
Salvianolic acid A acts as a herpes simplex virus dual inhibitor by blocking glycoprotein B-mediated adsorption and membrane fusion 丹酚酸A通过阻断糖蛋白b介导的吸附和膜融合作为单纯疱疹病毒的双重抑制剂
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-25 DOI: 10.1016/j.phymed.2025.156910
Han Yan , Haihua Li , Xiayu Chen , Jie Wang , Jiayi Yang , Zhongqiu Xu , Cui Hao , Wei Wang
{"title":"Salvianolic acid A acts as a herpes simplex virus dual inhibitor by blocking glycoprotein B-mediated adsorption and membrane fusion","authors":"Han Yan ,&nbsp;Haihua Li ,&nbsp;Xiayu Chen ,&nbsp;Jie Wang ,&nbsp;Jiayi Yang ,&nbsp;Zhongqiu Xu ,&nbsp;Cui Hao ,&nbsp;Wei Wang","doi":"10.1016/j.phymed.2025.156910","DOIUrl":"10.1016/j.phymed.2025.156910","url":null,"abstract":"<div><h3>Background</h3><div>The development of novel anti-herpes simplex virus (HSV) agents with high efficacy and low toxicity is great importance. Salvianolic acid A (SAA), a stilbenoid caffeic acid trimer from <em>Salvia miltiorrhiza</em> Bunge roots, has shown broad-spectrum antiviral activities against enterovirus 71 (EV71), pseudorabies virus (PRV), and SARS-CoV-2. However, no studies on its anti-HSV activity have been reported yet.</div></div><div><h3>Purpose</h3><div>To investigate the anti-HSV effects of SAA through both <em>in vitro</em> and <em>in vivo</em> approaches and to elucidate its mechanisms of action.</div></div><div><h3>Methods</h3><div>The anti-HSV effects of SAA in <em>vitro</em> were determined by cytopathic effect (CPE) inhibition assay, western blot assay and viral plaque assay<em>.</em> The virucidal assay, drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA) and heparin binding assay investigated SAA’s anti-HSV mechanism. The <em>in vivo</em> anti-HSV efficacy of SAA was evaluated using murine model for intranasal HSV-1 encephalitis and vaginal HSV-2 infection model.</div></div><div><h3>Results</h3><div>SAA suppressed HSV-1 and HSV-2 multiplication in different cells with low toxicity, superior to acyclovir. SAA directly inactivates HSV by disrupting virion membrane. SAA interacts with viral surface glycoprotein B (gB) to block HSV adsorption and entry. SAA treatment significantly improved mice survival, attenuated inflammatory symptoms, and reduced viral titers in HSV-1 and HSV-2 infected mice.</div></div><div><h3>Conclusion</h3><div>SAA possesses significant anti-HSV effects <em>in vitro</em> and <em>in vivo</em> through interaction with gB to block HSV entry and cause HSV particle rupture and inactivation. These findings support its potential as a novel therapeutic agent for herpetic encephalitis and genital herpes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156910"},"PeriodicalIF":6.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185594","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}
引用次数: 0
Jianpi Huayu decoction enhances the antitumor effect of doxorubicin via piezo1-mediated autophagy in hepatocellular carcinoma 健脾化瘀汤通过piezo1介导肝癌细胞自噬增强阿霉素的抗肿瘤作用
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-25 DOI: 10.1016/j.phymed.2025.156908
Chongkai Fang , Silin Liu , Sijia Zhang , Hao Zheng , Guang Fang , Chuyao Chen , Ying Zhang , Ruiwei Yao , Xinqiu Chen , Rui Luo , Jing Li , Chong Zhong
{"title":"Jianpi Huayu decoction enhances the antitumor effect of doxorubicin via piezo1-mediated autophagy in hepatocellular carcinoma","authors":"Chongkai Fang ,&nbsp;Silin Liu ,&nbsp;Sijia Zhang ,&nbsp;Hao Zheng ,&nbsp;Guang Fang ,&nbsp;Chuyao Chen ,&nbsp;Ying Zhang ,&nbsp;Ruiwei Yao ,&nbsp;Xinqiu Chen ,&nbsp;Rui Luo ,&nbsp;Jing Li ,&nbsp;Chong Zhong","doi":"10.1016/j.phymed.2025.156908","DOIUrl":"10.1016/j.phymed.2025.156908","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) carries a poor prognosis, especially in advanced stages. Although Piezo1, a mechanosensitive ion channel, is linked to HCC progression, its underlying mechanisms and therapeutic potential remain poorly understood.</div></div><div><h3>Methods</h3><div>Piezo1 expression in HCC and its correlation with prognosis were assessed using TCGA and GEO datasets, along with clinical tissue samples. The role of Piezo1 in HCC malignancy and autophagy was investigated in MHCC97H cells via siRNA-mediated silencing. A DEN-induced Piezo1-knockout mouse model and an shPiezo1-transfected MHCC97H xenograft nude mouse model were also used to evaluate the role of Piezo1 in tumor development and growth. The effects of Jianpi Huayu decoction (JPHY), doxorubicin (DOX), and combined treatment on malignant phenotypes and autophagy were examined in MHCC97H cells as well as an allogeneic transplantation model. Shared pathways between JPHY and DOX were identified by network pharmacology analysis and validated by molecular biology experiments. Molecular docking studies analyzed interactions between JPHY active components and Piezo1.</div></div><div><h3>Results</h3><div>Piezo1 was overexpressed in HCC tissues and correlated with poor prognosis. Piezo1 knockdown suppressed malignancy and enhanced autophagy in MHCC97H cells. In Piezo1<sup>+/−</sup> mice, the size and number of DEN-induced liver tumors were reduced by approximately 60 % and 45 %, respectively. Tumor growth was also suppressed in nude mice transplanted with shPiezo1-transfected MHCC97H cells. JPHY combined with DOX enhanced the antitumor effect and increased treatment sensitivity. Network pharmacology analysis revealed common targets of JPHY and DOX, enriched in the PI3K/AKT pathway. Both JPHY and DOX downregulated Piezo1 expression and inhibited the PI3K/AKT/mTOR pathway, while the combination demonstrated an even greater efficacy. The combination of JPHY and DOX reduced xenograft tumor size by approximately 40 % compared to DOX alone, without apparent hepatic or renal toxicity.</div></div><div><h3>Conclusion</h3><div>This study uncovers a novel mechanism by which JPHY enhances DOX sensitivity in HCC, acting through modulation of Piezo1-mediated autophagy via the PI3K/AKT/mTOR pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156908"},"PeriodicalIF":6.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185591","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}
引用次数: 0
Schisandrol B alleviated diabetic cardiac injury by inhibiting ferroptosis and improving lipid metabolism in mice 五味子酚B通过抑制铁下垂和改善小鼠脂质代谢减轻糖尿病小鼠心脏损伤
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-25 DOI: 10.1016/j.phymed.2025.156902
Zi-Chang Niu , Qi Jin , Qian-You Shen , Hui-hui Shi , Ye Shang , Xiao-Tong Guo , Meng Wang , Qin Yuan , Hao-Ping Mao
{"title":"Schisandrol B alleviated diabetic cardiac injury by inhibiting ferroptosis and improving lipid metabolism in mice","authors":"Zi-Chang Niu ,&nbsp;Qi Jin ,&nbsp;Qian-You Shen ,&nbsp;Hui-hui Shi ,&nbsp;Ye Shang ,&nbsp;Xiao-Tong Guo ,&nbsp;Meng Wang ,&nbsp;Qin Yuan ,&nbsp;Hao-Ping Mao","doi":"10.1016/j.phymed.2025.156902","DOIUrl":"10.1016/j.phymed.2025.156902","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic cardiomyopathy (DCM) is a major complication of diabetes mellitus, highlighting the need to elucidate its pathogenesis and explore potential therapeutic interventions.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the cardioprotective mechanisms of SolB in DCM using metabolomic and transcriptomic approaches.</div></div><div><h3>Methods</h3><div>A DCM mouse model was induced by a high-fat diet combined with streptozotocin (STZ) administration. Cardiac function was assessed, and myocardial structure was examined via echocardiography and HE staining after 10 weeks of SolB treatment. Serum metabolomics and cardiac transcriptomics were performed to identify differentially expressed metabolites and genes, respectively, followed by correlation analysis. Ferroptosis-related proteins were detected by Western blotting (WB). In vitro, H9c2 cells exposed to palmitic acid and high glucose were used to evaluate the effects of SolB on cell viability, ATP production, oxygen consumption, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Ferroptosis inducer and inhibitor were employed to further explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>SolB did not significantly alter blood glucose levels but markedly improved cardiac function and myocardial structure. Metabolomic analysis revealed that SolB modulated serum metabolic pathways, including carnitine synthesis and fatty acid oxidation et al. Transcriptomic data indicated that SolB influenced ferroptosis-related pathways. Integrated analysis demonstrated that SolB regulated fatty acid degradation, glutathione metabolism, and cysteine and methionine catabolism. In H9c2 cells, SolB enhanced cell viability, suppressed ferroptosis, reduced lactate dehydrogenase (LDH) release, and improved mitochondrial function.</div></div><div><h3>Conclusions</h3><div>SolB ameliorates diabetic myocardial injury by inhibiting ferroptosis and improving myocardial lipid metabolism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156902"},"PeriodicalIF":6.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185595","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}
引用次数: 0
Paeonol ameliorates diabetic nephropathy by promoting TFEB-mediated lysosome biogenesis and lipophagy 丹皮酚通过促进tfeb介导的溶酶体生物生成和脂质吞噬来改善糖尿病肾病
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-24 DOI: 10.1016/j.phymed.2025.156901
Sinan Ai , Jiayin Tao , Yaoxian Wang , Jingwei Zhou , Weijing Liu , Xi Li , Lin Wang , Jinyi Hou , Leying Zhao , Zhen Wang , Liang Peng
{"title":"Paeonol ameliorates diabetic nephropathy by promoting TFEB-mediated lysosome biogenesis and lipophagy","authors":"Sinan Ai ,&nbsp;Jiayin Tao ,&nbsp;Yaoxian Wang ,&nbsp;Jingwei Zhou ,&nbsp;Weijing Liu ,&nbsp;Xi Li ,&nbsp;Lin Wang ,&nbsp;Jinyi Hou ,&nbsp;Leying Zhao ,&nbsp;Zhen Wang ,&nbsp;Liang Peng","doi":"10.1016/j.phymed.2025.156901","DOIUrl":"10.1016/j.phymed.2025.156901","url":null,"abstract":"<div><h3>Rationale</h3><div>Diabetic nephropathy (DN) is a significant clinical and public health burden worldwide whose magnitude underscores the urgent need for more effective treatment options. Excessive lipid accumulation in renal tubular cells leads to their injury and dysfunction, thereby contributing to DN progression, suggesting that the alleviation of renal tubular lipid accumulation is a potential strategy for treating DN.</div></div><div><h3>Methods</h3><div>The effects of paeonol (PAE), a natural phenolic compound, on renal tubular lipid accumulation were evaluated using a glucolipotoxicity-treated HK-2 cell line and C57BL/6 J mice treated with streptozotocin (STZ) injection combined with a high-fat diet (HFD). Autophagic flux and lipophagy were assessed through immunofluorescence, adenoviral mRFP-GFP-LC3 transfection, and western blotting. Small interfering RNA (siRNA) was used for in vitro experiments to silence Tfeb in HK-2 cells, while a Cre-loxP system was employed to induce Tfeb knockout specifically in renal tubules in vivo, to validate the therapeutic target of PAE. RNA sequencing, pulldown assays, surface plasmon resonance (SPR), and molecular docking were utilized to further explore the specific molecular mechanisms involved.</div></div><div><h3>Results</h3><div>We found that PAE dose-dependently alleviated renal tubular lipid accumulation in glucolipotoxicity-treated HK-2 cells and the DN mouse model. Mechanistically, PAE directly binds to RHEB, functioning as an mTOR suppressor, thereby activating TFEB to promote lysosome biogenesis and lipophagy, subsequently alleviating renal tubular lipid accumulation and DN progression.</div></div><div><h3>Conclusions</h3><div>Per our findings, PAE holds promise as a therapeutic agent for DN, with the unique mechanism of activating renal TFEB-mediated lipophagy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156901"},"PeriodicalIF":6.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203582","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}
引用次数: 0
Disruption of cholesterol homeostasis triggers NLRP3-cGAS-STING axis-dependent hepatic fibrosis and honokiol intervention effects 胆固醇稳态的破坏触发NLRP3-cGAS-STING轴依赖性肝纤维化和檀香醇干预效应
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-24 DOI: 10.1016/j.phymed.2025.156904
Zhilei Wang , Jingwen Liu , Yu Mou , Xianglu Zhou , Wenhao Liao , Yuchen Li , Yong Liu , Jianyuan Tang
{"title":"Disruption of cholesterol homeostasis triggers NLRP3-cGAS-STING axis-dependent hepatic fibrosis and honokiol intervention effects","authors":"Zhilei Wang ,&nbsp;Jingwen Liu ,&nbsp;Yu Mou ,&nbsp;Xianglu Zhou ,&nbsp;Wenhao Liao ,&nbsp;Yuchen Li ,&nbsp;Yong Liu ,&nbsp;Jianyuan Tang","doi":"10.1016/j.phymed.2025.156904","DOIUrl":"10.1016/j.phymed.2025.156904","url":null,"abstract":"<div><h3>Background</h3><div>Maintaining cholesterol homeostasis is crucial for sustaining human health and physiological function. Although the detrimental effects of chronic cholesterol overload on hepatic injury and fibrosis are well documented, the molecular mechanisms driving this pathology remain incompletely understood.</div></div><div><h3>Purpose</h3><div>This study investigates the mechanistic role of chronic cholesterol overload in driving liver fibrosis and evaluates the therapeutic efficacy of honokiol as a targeted intervention.</div></div><div><h3>Study design and methods</h3><div>High-cholesterol models induced by cholesterol and 25-hydroxycholesterol in human HepG2 cells or induced by cholesterol crystals in mouse bone marrow-derived macrophages were established. We also examined the effect of cholesterol on the livers of mice following a 20-week regimen of high-cholesterol diets.</div></div><div><h3>Results</h3><div>Excess cholesterol interfered with normal cholesterol metabolism both <em>in vitro</em> and <em>in vivo</em>, and led to liver damage and fibrosis <em>in vivo</em>. Further research showed that cholesterol exposure triggered NLRP3 inflammasome activation and programmed cell death called pyroptosis; induced an increase in mitochondrial ROS and a disruption of intracellular redox homeostasis, followed by the opening of the mitochondrial permeability transition pore; and finally induced cellular DNA damage, resulting in the translocation of the double-stranded DNA fragment into the cytoplasm and the activation of the DNA-sensing adaptor STING. The activation of the NLRP3-cGAS-STING axis initiated the downstream cascade reaction and up-regulated the expression of pro-inflammatory cytokines, including IL-1β, TNF-α, and IFN-β, thus facilitating liver damage and fibrosis. Furthermore, honokiol, an active ingredient in <em>Magnolia officinalis</em>, could alleviate liver damage and fibrosis by blocking NLRP3 inflammasome activation, pyroptosis, and the cGAS-STING pathway.</div></div><div><h3>Conclusion</h3><div>Systematic evidence shows that cholesterol induces liver fibrosis through the activation of the NLRP3-cGAS-STING signaling axis and that honokiol demonstrates interventional efficacy in mitigating this process.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156904"},"PeriodicalIF":6.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177820","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}
引用次数: 0
Calycosin inhibits lytic replication of Kaposi’s sarcoma-associated herpesvirus by downregulating early growth response 1 毛蕊异黄酮通过下调早期生长反应抑制卡波西肉瘤相关疱疹病毒的裂解复制
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-24 DOI: 10.1016/j.phymed.2025.156884
Yue Liu , Jiale Wang , Si-Wei Cheng , Xin Chen , Zhantao Bai , Yan-Heng Zhou
{"title":"Calycosin inhibits lytic replication of Kaposi’s sarcoma-associated herpesvirus by downregulating early growth response 1","authors":"Yue Liu ,&nbsp;Jiale Wang ,&nbsp;Si-Wei Cheng ,&nbsp;Xin Chen ,&nbsp;Zhantao Bai ,&nbsp;Yan-Heng Zhou","doi":"10.1016/j.phymed.2025.156884","DOIUrl":"10.1016/j.phymed.2025.156884","url":null,"abstract":"<div><h3>Background</h3><div>Kaposi’s sarcoma-associated herpesvirus (KSHV) is linked to several diseases, including primary effusion lymphoma, multicentric Castleman’s disease, and KSHV inflammatory cytokine syndrome. Current treatment options for KSHV-associated diseases are sometimes ineffective, and antiviral drugs are still lacking. Calycosin (CA), an O-methylated isoflavone found in <em>Astragalus membranaceus,</em> has previously demonstrated strong activity against coxsackievirus B3 (CVB3) and human immunodeficiency virus (HIV), but its effect against KSHV has not been previously reported.</div></div><div><h3>Methods</h3><div>Viral lytic replication was evaluated via both the relative quantification of viral DNA within cells and the absolute quantification of viral genomes in cellular supernatants. RNA sequencing was employed to identify key genes involved in the anti-KSHV process for CA. Real-time PCR and western blotting were utilized to elucidate gene expression. Ectopic gene expression was delivered by plasmid transfection or lentivirus transduction.</div></div><div><h3>Results</h3><div>CA dose-dependently inhibited KSHV lytic replication in both KSHV latently infected cells and <em>de novo</em>-infected human umbilical vein endothelial cells (HUVECs) without causing cytotoxicity. Further investigation of the anti-KSHV mechanism revealed that CA downregulated the expression of early growth response 1 (EGR1), consequently suppressing the promoter activity of replication and transcription activator (RTA), which is a crucial switch triggering KSHV from latency to lytic replication. Additionally, CA suppressed inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) induced by KSHV infection, and this suppression was EGR1 dependent.</div></div><div><h3>Conclusion</h3><div>This study for the first time reported the function and mechanism of CA in inhibiting the lytic replication of KSHV, providing a new candidate for anti-KSHV agents. Moreover, these findings expand the understanding of the pharmacological values of CA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156884"},"PeriodicalIF":6.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177655","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}
引用次数: 0
Predicting the molecular mechanism of ginger targeting PRMT1/BTG2 axis to inhibit gastric cancer based on WGCNA and machine algorithms 基于WGCNA和机器算法预测生姜靶向PRMT1/BTG2轴抑制胃癌的分子机制
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-05-24 DOI: 10.1016/j.phymed.2025.156892
Guoqing Chen , Boyun Gou , Yuhua Du , Ziying Zhou , Yuting Bai , Yi Yang , Yi Nan , Ling Yuan
{"title":"Predicting the molecular mechanism of ginger targeting PRMT1/BTG2 axis to inhibit gastric cancer based on WGCNA and machine algorithms","authors":"Guoqing Chen ,&nbsp;Boyun Gou ,&nbsp;Yuhua Du ,&nbsp;Ziying Zhou ,&nbsp;Yuting Bai ,&nbsp;Yi Yang ,&nbsp;Yi Nan ,&nbsp;Ling Yuan","doi":"10.1016/j.phymed.2025.156892","DOIUrl":"10.1016/j.phymed.2025.156892","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to screen the biomarkers of ginger against gastric cancer (GC) by network pharmacology, WGCNA and machine algorithms. To find the upstream transcription factors and downstream signaling proteins constituting the signaling axis, so as to predict the possible mechanism of action of ginger against GC.</div></div><div><h3>Methods</h3><div>Ginger was screened for active ingredients and targets through public databases. GC genes were screened using disease database, GEO database and WGCNA. The intersection of the four was taken to obtain the potential core genes. Machine algorithms was used to screen the core genes. Clinical relevance analysis, gene mutation relationship, epigenetic regulation analysis, immune infiltration analysis and molecular docking validation were performed on the core genes. Find its upstream transcription factors and downstream signaling proteins through database.</div></div><div><h3>Results</h3><div>35 intersecting genes were obtained by databases and WGCNA analysis. Machine algorithms and PPI were combined to finally screen the core gene PRMT1. The upstream transcription factor of PRMT1 was identified as EGR1 and the downstream protein as BTG2 by database and molecular docking.</div></div><div><h3>Conclusion</h3><div>In this study, we found that PRMT1 could be used as a biomarker for ginger against GC using network pharmacology, WGCNA and machine algorithms. We hypothesized that ginger may exert antitumor effects through PRMT1/BTG2, providing new insights into the pharmacological mechanism of ginger against GC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156892"},"PeriodicalIF":6.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177817","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}
引用次数: 0
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