Phytomedicine最新文献

{"title":"Naturally-occurring carnosic acid as a promising therapeutic agent for skin inflammation via targeting STAT1","authors":"Aike Wu ,&nbsp;Yunying Wang ,&nbsp;Rui Mao ,&nbsp;Zixin Tan ,&nbsp;San Xu ,&nbsp;Juan Long ,&nbsp;Qian Wang ,&nbsp;Zhixiang Zhao ,&nbsp;Hongfu Xie ,&nbsp;Zhili Deng ,&nbsp;Ji Li ,&nbsp;Mengting Chen","doi":"10.1016/j.phymed.2025.156442","DOIUrl":"10.1016/j.phymed.2025.156442","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis and rosacea are prevalent chronic inflammatory skin disorders driven by aberrant interactions between skin-resident keratinocytes and immune cells. Natural products represent a largely untapped source of novel therapeutic agents for various diseases. This study aimed to identify an effective natural product for treating psoriasis and rosacea and to elucidate its underlying mechanism of action.</div></div><div><h3>Methods</h3><div>Bioinformatics and network pharmacology approaches were employed to identify potential drug candidates for these conditions. Psoriasis-like and rosacea-like inflammation models were established in mice to assess the <em>in vivo</em> therapeutic effects of carnosic acid. <em>In vitro</em> experiments were performed to investigate the molecular mechanisms underlying carnosic acid's anti-inflammatory activity.</div></div><div><h3>Results</h3><div>Through bioinformatics and network pharmacology, carnosic acid, a plant-derived phenolic diterpene, was identified as a promising candidate for these skin disorders. Functional assays demonstrated that carnosic acid effectively inhibited skin inflammation in both imiquimod-induced psoriasis and LL37-induced rosacea mouse models. Mechanistically, carnosic acid bound directly to STAT1, inhibiting its phosphorylation and subsequent transcriptional activation, which led to a reduction in the production of STAT1-mediated inflammatory factors in keratinocytes. Topical application of carnosic acid significantly alleviated clinical symptoms in both psoriasis and rosacea models.</div></div><div><h3>Conclusion</h3><div>These findings suggest that carnosic acid holds potential as a therapeutic agent for STAT1-mediated skin inflammation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156442"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304862","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":"Integrated UHPLC-Q-exactive orbitrap HRMS and serum pharmacochemistry for the investigation of anti-hepatic fibrosis effect of Baoganning Decoction","authors":"Kaili Deng ,&nbsp;Min Li ,&nbsp;Liangliang Xiang ,&nbsp;Yuhua Wang ,&nbsp;Yamei Li ,&nbsp;Junya Wen ,&nbsp;Yuanyuan Li ,&nbsp;Shanshan Kuang ,&nbsp;Jinjie Wen ,&nbsp;Chuying Zhou ,&nbsp;Sha Huang ,&nbsp;Zhiping Lv","doi":"10.1016/j.phymed.2025.156363","DOIUrl":"10.1016/j.phymed.2025.156363","url":null,"abstract":"<div><h3>Background</h3><div>Early intervention in hepatic fibrosis (HF) is critical to reducing the risk of cirrhosis-related mortality and hepatocellular cancer. However, treating fibrosis has proven to be more challenging, with no approved anti-fibrotic therapies currently available for HF. Traditional Chinese medicines (TCMs) hold significant potential for the management of HF.</div></div><div><h3>Purpose</h3><div>This study aims to propose a systematic approach for investigating the pharmacological basis of Baoganning (BGN) Decoction, providing empirical evidence to support future research on its targets and mechanisms of BGN.</div></div><div><h3>Study design</h3><div>Ultrahigh-performance liquid chromatography coupled with high- resolution mass spectrometry (UPLC-HRMS) was employed to analyze the chemical composition of BGN. Key compounds were investigated using disease databases to predict relevant targets, followed by molecular docking and molecular dynamics simulations to explore molecular-level interactions. The efficacy and critical targets of BGN were validated through <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Methods</h3><div>UPLC-HRMS was used to identify the chemical composition of the BGN, and serum pharmacology determined the active chemical constituents in rat plasma. Zebrafish, HSC-T6 cells, JS-1 cell line and mice served as experimental models to evaluate the antifibrotic effects of BGN.</div></div><div><h3>Results</h3><div>BGN demonstrated significant antifibrotic effect <em>in vivo</em> and <em>in vitro</em> models. A total of 757 compounds were identified in BGN, with 18 prototypical components and metabolites detected. Three compounds-quillaic acid, methyl cholate, and 3<em>β</em>-hydroxy-5-cholenoic exhibited dose-dependent inhibitory effects on HF. Molecular docking studies revealed stable interactions between these compounds and predicted targets. Additionally, the screened components effectively reduced the expression of ‌α-SMA and COL-I in both a cellular model and a zebrafish fibrosis model in a dose-dependent manner.</div></div><div><h3>Conclusion</h3><div>The comprehensive analysis of BGN's chemical composition and its metabolic processes provides valuable insights into its pharmacological effects. These findings support the potential clinical and international application of BGN in treating hepatic fibrosis and improving patient outcomes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156363"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971942","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":"Schisandrol B alleviates depression-like behavior in mice by regulating bile acid homeostasis in the brain-liver-gut axis via the pregnane X receptor","authors":"Peng Wang ,&nbsp;Hui Ouyang ,&nbsp;Guofang Bi ,&nbsp;Fengting Liang ,&nbsp;Shuang Hu ,&nbsp;Chenghua Wu ,&nbsp;Xiaowen Jiang ,&nbsp;Wenhong Zhou ,&nbsp;Dan Li ,&nbsp;Shuaishuai Zhang ,&nbsp;Xiao Yang ,&nbsp;Mingliang Zhao ,&nbsp;Jian-Hong Fang ,&nbsp;Haitao Wang ,&nbsp;Wei Jia ,&nbsp;Zheng-jiang Zhu ,&nbsp;Huichang Bi","doi":"10.1016/j.phymed.2024.156340","DOIUrl":"10.1016/j.phymed.2024.156340","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from <em>Schisandra chinensis (Turcz.) Baill.</em> or <em>Schisandra sphenanthera Rehd.etWils,</em> is pivotal in regulating bile acid homeostasis via pregnane X receptor (PXR) in cholestasis. However, the potential of SolB in alleviating depression-like symptoms, its pharmacological effects, and the underlying mechanisms remain to be fully elucidated.</div></div><div><h3>Methods</h3><div>We confirmed the effect of SolB against depression induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) in mice. The role of SolB in bile acid homeostasis in depression was analyzed using the metabolomic. Gene analyses and 16S rRNA sequencing were employed to investigate the involvement of PXR. Experiments with <em>Pxr^−/−</em> mice were conducted to confirm the essential role of the PXR pathway in SolB's antidepressant effects.</div></div><div><h3>Results</h3><div>SolB treatment significantly increased sucrose consumption in the SPT and the locomotor activity in the OFT, while decreasing immobility time in the FST and TST in mice exposed to CRS and CUMS. Additionally, SolB treatment significantly preserved the integrity of the dendritic spine, elevated synaptic protein PSD95 levels, and augmented CREB/BDNF expression. Metabolomic and gene analyses indicated that SolB treatment significantly facilitated bile acid metabolism, promoted intestinal bile acid efflux, decreased hippocampal levels of the secondary bile acids DCA and TLCA, and upregulated expression of the PXR target proteins CYP3A11, SULT2A1, MRP2, and OATP1B1 in the liver, and MRP2 and MDR1 in hippocampus, which are integral to bile acid homeostasis. 16S rRNA sequencing revealed that SolB reduced the abundance of the bile salt hydrolase (BSH)-producing bacteria <em>Lactobacillus johnsonii</em> and <em>Bacteroides fragilis</em> and subsequently decreased the production of TLCA and DCA. Moreover, SolB failed to protect against depression induced by CRS in <em>Pxr</em>-null mice, suggesting that the antidepressant effect of SolB was PXR-dependent.</div></div><div><h3>Conclusions</h3><div>These results provide direct evidence of the antidepressant effect of SolB via activation of PXR to regulate bile acid homeostasis in the brain-liver-gut axis, suggesting that SolB may serve as a novel potential target for preventing and treating depression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156340"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984643","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":"Mechanism exploration of Wenshen Jianpi Decoction on renoprotection in diabetic nephropathy via transcriptomics and metabolomics","authors":"Yingping Deng ,&nbsp;Guanghui Zhong ,&nbsp;Tinglong Jin,&nbsp;Jin Wang,&nbsp;Xin Peng,&nbsp;Kai Zhou,&nbsp;Xiabo Chen,&nbsp;Xiaodan Cao","doi":"10.1016/j.phymed.2025.156446","DOIUrl":"10.1016/j.phymed.2025.156446","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is a severe chronic microvascular complications of diabetes mellitus and the leading cause of end-stage renal disease. Although many therapeutic approaches have been developed for treatment of DN, there is still a risk of disease progression. Wenshen Jianpi Decoction (WSJPD), a traditional Chinese medicine, have demonstrated considerable clinical efficacy in treating DN. However, the therapeutic mechanisms of WSJPD remain unclear.</div></div><div><h3>Purpose</h3><div>The study aimed to assess the potential anti-renal injury effects of WSJPD as well as the underlying mechanism.</div></div><div><h3>Methods</h3><div>Network pharmacology was performed to predict the potential targets of WSJPD in DN. Subsequently, HE, PAS, Masson staining, TEM and ELISA were used to assess the effects of WSJPD on renal injury in DN rats. Transcriptomics, metabolomics, and qRT-PCR were employed to analyze the potential mechanism.</div></div><div><h3>Results</h3><div>Network pharmacology analysis revealed that WSJPD might exert a beneficial impact on renal inflammation via the AGE-RAGE signaling pathway. The results of animal experiments indicated that WSJPD had a renoprotective effect by renal dysfunction improvement, inflammation inhibition, glycogen accumulation and podocyte injury suppression.Transcriptomic measures discovered that 212 genes were up-regulated in the DN model group and down-regulated in the WSJPD group. Conversely, 80 genes were down-regulated in the DN model group and up-regulated in the WSJPD group. Moreover, 14 metabolites from rat serum samples were identified as candidate biomarkers. Further analysis demonstrated that WSJPD ameliorated the metabolic disorders and exerted a protective effect by up-regulation of uridine-mediated pyrimidine metabolism, inhibition of inflammation mediated by the NF-κB and TNF signaling pathways, and inhibition of oxidative stress and inflammation mediated by the AGE-RAGE signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings showed that WSJPD ameliorated renal damage in DN model rats by regulating kidney pyrimidine metabolism, inflammation-related pathways, and AGE-RAGE signaling pathway. The potential renoprotective effects were verified by histopathology, ELISA, and qRT-PCR. This study not only support a foundation for interpretation of the therapeutic effects of WSJPD on renal lesions, but also provide data support for further explorations of the novel compound preparations to improve renal function in DN.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156446"},"PeriodicalIF":6.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304861","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":"Sanzi Yangqin Decoction improved acute lung injury by regulating the TLR2-mediated NF-κB/NLRP3 signaling pathway and inhibiting the activation of NLRP3 inflammasome","authors":"Anna Gan ,&nbsp;Haimiao Chen ,&nbsp;Fei Lin ,&nbsp;Ruixuan Wang ,&nbsp;Bo Wu ,&nbsp;Tingxu Yan ,&nbsp;Ying Jia","doi":"10.1016/j.phymed.2025.156438","DOIUrl":"10.1016/j.phymed.2025.156438","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated.</div></div><div><h3>Purpose</h3><div>This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI.</div></div><div><h3>Methods</h3><div>The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI.</div></div><div><h3>Results</h3><div>This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis.</div></div><div><h3>Conclusions</h3><div>This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156438"},"PeriodicalIF":6.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099483","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":"Hepatotoxicity of Phytolacca acinosa Roxb mediated by phytolaccagenin via ferroptosis/PPAR/P53/arachidonic acid metabolism","authors":"Muyao Cui ,&nbsp;Yao Zhang ,&nbsp;Yang Tang ,&nbsp;Qiqi Fan ,&nbsp;Xiaolu Chen ,&nbsp;Jiaqi Li ,&nbsp;Chuanqi Qiao ,&nbsp;Xue Chen ,&nbsp;Ruichao Lin ,&nbsp;Xue Yu ,&nbsp;Chongjun Zhao","doi":"10.1016/j.phymed.2025.156433","DOIUrl":"10.1016/j.phymed.2025.156433","url":null,"abstract":"<div><h3>Background</h3><div>The traditional Chinese medicine Phytolacca acinosa Roxb (PAR), known as Shanglu, possesses recognized therapeutic benefits against many diseases. PAR is also hepatotoxic, making it a major public health problem. However, the specific toxic substances and molecular mechanisms of PAR remain unclear. Therefore, appropriate animal models and methods are essential to confirm the toxic components and related mechanisms of PAR.</div></div><div><h3>Methods</h3><div>L-02 cells and zebrafish larvae at 4 days post-fertilization (4 dpf) were used as models and treated with various concentrations of phytolaccagenin (Phy), esculentoside A (EsA), and esculentoside H (EsH). The hepatotoxicity of three samples was assessed based on liver phenotype, pathological assessments, and biochemical index in zebrafish and proliferative activity, apoptosis level, and biochemical index in L02 cells. The transcriptomic technique was used to explore the related signaling pathways and potential mechanisms in vitro and in zebrafish , and the findings were validated by RT-PCR.</div></div><div><h3>Results</h3><div>The results of acute toxicity tests indicated that Phy exhibited substantially more severe hepatotoxicity than EsA, while EsH did not lead to any obvious toxic effects. Especially, under sublethal exposure (&lt;LC10), both Phy and EsA induced similar liver damage in zebrafish and L-02 cells, increasing mortality, disrupting morphology, enhancing apoptosis, altering liver enzyme levels, and leading to significant structural changes in cells and zebrafish. Multiomics analysis of 605 genes in L-02 cells and 780 genes in zebrafish showed that exposure to Phy significantly altered gene expression in various biological processes. Further enrichment analysis demonstrated that Phy predominantly affects the P53apoptosiscell cycle arrest, ferroptosis, PPAR signaling, and arachidonic acid metabolism, leading to notable cellular damage.</div></div><div><h3>Conclusion</h3><div>This study identified Phy as a key hepatotoxic component of PAR. Furthermore, using transcriptomic techniques, we preliminarily investigated the hepatotoxic mechanisms of Phy in vitro and in vivo. The results of the present study showed that Phy affects several signaling pathways, including those involved in lipid metabolism, oxidative stress, and apoptosis, finally leading to hepatotoxicity. These findings provide invaluable insights into the safe use of PAR in clinical settings.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156433"},"PeriodicalIF":6.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075062","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":"Isovaleroylbinankadsurin A ameliorates atherosclerosis and restenosis by promoting LXRα signaling pathway and inhibiting TGF-β1 and FHL1 signaling pathways","authors":"Yaning Shi ,&nbsp;Leping Liu ,&nbsp;Yongzhen Gong ,&nbsp;Chanjuan Zhang ,&nbsp;Yupei Yang ,&nbsp;Wei Wang ,&nbsp;Li Qin","doi":"10.1016/j.phymed.2025.156451","DOIUrl":"10.1016/j.phymed.2025.156451","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis is a leading factor in the development of several cardiovascular conditions, including ischemic heart disease, stroke, and peripheral vascular disease. A defining characteristic of atherosclerosis is the formation of macrophages and vascular smooth muscle cells (VSMCs)-derived foam cells in plaques. Angioplasty can effectively remove atherosclerotic plaque, while it may lead to restenosis. A crucial pathological feature of restenosis is neointimal formation, which is driven by the phenotypic change, growth, and migration of VSMCs. Nonetheless, there are only a handful of effective strategies. Kadsura coccinea is a folk Chinese herb mainly used to treat rheumatism, chronic gastritis, bruises, and dysmenorrhea. Isovaleroylbinankadsurin A (ISBA), isolated from Kadsura coccinea roots, is a dibenzocyclooctadiene lignan that has recently been shown to be beneficial for myocardial ischemia-reperfusion injury. However, its protective effects on atherosclerosis and restenosis remain unknown.</div></div><div><h3>Purpose</h3><div>To investigate the effects and related mechanisms of ISBA on atherosclerosis and restenosis.</div></div><div><h3>Methods</h3><div>Foam cells were induced by ox-LDL <em>in vitro</em>, and a high-fat diet was administered to ApoE^-/- mice. HE staining was applied to evaluate the morphology of vascular tissues. Lipid accumulation of plaques and foam cells was measured using BODIPY-cholesterol, DiI-ox-LDL, Oil Red O staining, and cholesterol quantification tests. A mouse model of femoral artery injury and an <em>in vitro</em> VSMC proliferation model were established. The CCK-8, EdU, plate clone formation, and wound-healing assays were used to evaluate cell viability and migration. Western blot analysis and immunohistochemistry were employed to assess the levels of crucial proteins in ISBA mediating atherosclerosis and restenosis.</div></div><div><h3>Results</h3><div>We found for the first time that ISBA could significantly alleviate atherosclerosis and restenosis. Mechanistically, ISBA inhibited lipid accumulation and reduced foam cell formation through the activation of LXRα/ABCA1 signaling pathway, which contributed to preventing atherosclerosis. In addition, ISBA could also suppress the phenotypic switch, proliferation, and migration of VSMCs through repressing TGF-β1/ERK1/2/CTGF and FHL1/ERK1/2/CTGF signaling pathways, thereby mitigating neointimal formation and restenosis.</div></div><div><h3>Conclusion</h3><div>This study offers a groundbreaking and expanded exploration of the pharmacological effects of ISBA. ISBA may be a novel therapeutic drug to prevent atherosclerosis and restenosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156451"},"PeriodicalIF":6.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304847","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":"Inhibition of citrate transport reduces HIF-1α/GABA-T-mediated succinate accumulation in macrophages: The role of astragaloside IV in ischemic stroke","authors":"Yi Li ,&nbsp;Yu-Ning Zhang ,&nbsp;Pei-Lin Zhang,&nbsp;Yu-Chen Li,&nbsp;Lu Zhang,&nbsp;Hua Yang,&nbsp;Ping Li","doi":"10.1016/j.phymed.2025.156449","DOIUrl":"10.1016/j.phymed.2025.156449","url":null,"abstract":"<div><h3>Background</h3><div>The occurrence of ischemic stroke is closely associated with the inflammatory infiltration of peripheral monocytes/macrophages, and the inflammatory activation of macrophages is often affected by metabolic reprogramming. The Slc25a1 regulates mitochondrial citrate transport and has been shown to affect cell proliferation and migration in cancer. Astragaloside IV exhibits significant anti-inflammatory activity and improves ischemic stroke, but its regulatory effect on macrophage metabolic reprogramming has not been elucidated.</div></div><div><h3>Objectives</h3><div>This study aims to explore the effect of astragaloside IV on ischemic stroke injury from the perspective of Slc25a1-mediated cellular metabolic reprogramming.</div></div><div><h3>Methods</h3><div>A total of 170 mice were used to establish the middle cerebral artery occlusion (MCAO) model. The therapeutic effect of astragaloside IV was evaluated by neurobehavioral scores and infarct volume, with its impact further verified through the depletion of peripheral macrophages. The modulation of Slc25a1 by astragaloside IV and its influence on macrophages were investigated in mouse bone marrow-derived macrophages (BMDMs) and peripheral blood mononuclear cell-derived macrophages (PBMC-derived macrophages).</div></div><div><h3>Results</h3><div>Astragaloside IV significantly mitigated neurological impairment and reduced cerebral infarction volume in MCAO mice by inhibition of peripheral monocytes/macrophage inflammatory infiltration. In activated BMDMs and PBMC-derived macrophages, astragaloside IV interacted with Slc25a1, attenuated citrate transport, maintained mitochondrial function, therefore enhancing the shift from the M1- to M2-like macrophages. Mechanistically, astragaloside IV inhibited the transcriptional regulation of HIF-1α on GABA-T <em>via</em> citate-mediated histone H3 and H4 deacetylation and promoted the resumption of the broken TCA cycle and mitochondrial OXPHOS in macrophages.</div></div><div><h3>Conclusions</h3><div>Our study unveiled a therapeutic strategy for ischemic stroke by intervening in the inflammatory infiltration of peripheral monocytes/macrophages. Astragaloside IV, by binding to the mitochondrial citrate transporter Slc25a1, maintained the homeostasis of the TCA cycle and mitochondrial function, ultimately blocking the inflammation of peripheral macrophages to ameliorate ischemic stroke damage. This discovery provides data support for expanding the clinical application of astragaloside IV and offers research insights into the external treatment of encephalopathy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156449"},"PeriodicalIF":6.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350495","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":"Norwogonin attenuates LPS-induced acute lung injury through inhibiting Src/AKT1/NF-κB signaling pathway","authors":"Tianjiao Cao ,&nbsp;An-Qing Li ,&nbsp;Yi Zhang ,&nbsp;Ting-Ting Xie ,&nbsp;Ding-Zhou Weng ,&nbsp;Chun-Shui Pan ,&nbsp;Li Yan ,&nbsp;Kai Sun ,&nbsp;Di Wang ,&nbsp;Jing-Yan Han ,&nbsp;Jian Liu","doi":"10.1016/j.phymed.2025.156432","DOIUrl":"10.1016/j.phymed.2025.156432","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Acute lung injury (ALI) has emerged as a critical illness, with sepsis-related ALI accounting for &gt;80 %. In the context of bacterial infection, damage to the pulmonary microvascular barrier leads to inflammatory cell infiltration and plasma component extravasation into pulmonary interstitium. This disruption impairs gas exchange, resulting in hypoxemia. Norwogonin (NWG), a natural plant flavone, has shown potential anti-inflammatory and antioxidative effects. However, whether it could ameliorate sepsis-related ALI and the potential mechanism remains unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to investigate the effects and underlying mechanisms of NWG in treating sepsis-related ALI.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Male Wistar rats (200–220 g) were used to establish sepsis-related ALI model via intraperitoneal injection of lipopolysaccharide (LPS). Vital signs and arterial blood gas analysis, HE and immunohistochemistry staining, dynamic visualization of the microcirculatory system to observe FITC-dextran leakage and leukocyte adhesion, ELISA assay of inflammatory cytokines, Evans Blue extravasation, measurement of total protein content in bronchoalveolar lavage fluid, determination of the Wet/Dry weight ratio, Western blot and RT-qPCR analysis were used to evaluate NWG's effects and the potential mechanism. Additionally, we employed network pharmacology and molecular docking to identify and evaluate the interaction between NWG and the key targets of ALI. Surface plasmon resonance and enzyme activity assay were utilized to confirm the direct interaction between NWG and the potential targets.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;NWG administration improved the vital signs of LPS-stimulated rats. Exposure to LPS led to deteriorated arterial blood gas analysis, prominent lung morphology destruction, neutrophil and M1 macrophage infiltration, leukocyte adhesion, FITC-dextran leakage, elevated secretion of inflammatory cytokines, and aggravated lung edema. NWG intervention effectively mitigated these changes. Furthermore, NWG suppressed NF-κB/NLRP3 signaling and up-regulated endothelial junction proteins. Network pharmacology analysis and molecular docking identified five top key targets: MMP-9, AKT1, COX-2, Src and JAK-2. Western blot and RT-qPCR results confirmed that NWG inhibited the Src/AKT1/NF-κB signaling pathway, and down-regulated the levels of inflammatory factors. Surface plasmon resonance revealed the direct binding between NWG and AKT1, COX-2 and Src, rather than MMP-9. Enzyme activity assay demonstrated that NWG inhibited the activity of AKT1, COX-2 and Src.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;NWG alleviated inflammation, restored pulmonary microvascular barrier function and improved LPS-induced ALI. These effects were mediated by inhibiting the Src/AKT1/NF-κB signaling pathway through direct targeting of Src, AKT1 and COX-2. Our study provided novel scientific evidence supporting","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156432"},"PeriodicalIF":6.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348267","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":"Bacopaside I, acting as an aquaporin 1 inhibitor, ameliorates rheumatoid arthritis via suppressing aquaporin 1-mediated autophagy","authors":"Yan Huang ,&nbsp;Meng-yuan Zhou ,&nbsp;Ling-ling Li ,&nbsp;Min Lv ,&nbsp;Ze-shan Xu ,&nbsp;Xin-jie Wu ,&nbsp;Sheng-long Gu ,&nbsp;Man-yu Zhang ,&nbsp;Li Cai ,&nbsp;Rong Li","doi":"10.1016/j.phymed.2025.156444","DOIUrl":"10.1016/j.phymed.2025.156444","url":null,"abstract":"<div><h3>Background</h3><div>Aquaporin 1 (AQP1) is a promising target for regulating fibroblast-like synoviocyte (FLS) behaviors in rheumatoid arthritis (RA). Bacopaside I (BSI), the main active compound of the herbal medicine <em>Bacopa monnieri</em> with anti-RA effects, inhibits tumor cell growth by blocking AQP1, but its potential use in RA is unclear.</div></div><div><h3>Purpose</h3><div>To address BSI's anti-RA effects and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We investigated BSI's therapeutic effects on TNF-α-induced RA FLS and identified AQP1 as its direct target through molecular docking, cellular thermal shift assay (CETSA), and AQP1 knockdown experiments. We studied BSI's impacts on rat adjuvant-induced arthritis (AIA) and synovial proliferation, apoptosis, and autophagy in AIA rat synovium. We explored the role of autophagy inhibition in BSI's effects in vitro and in vivo by co-treating with the autophagy activator rapamycin (Rapa) and/or the inhibitor 3-methyladenine (3-MA).</div></div><div><h3>Results</h3><div>BSI suppressed proliferation, promoted apoptosis, and reduced autophagy in TNF-α-stimulated RA FLS. Notably, BSI's in vitro effects were reduced by Rapa and enhanced by 3-MA. The molecular docking and CETSA confirmed BSI's binding to AQP1, while AQP1 knockdown invalidated BSI's in vitro effects, further indicating AQP1 as the target of BSI. In vivo, BSI attenuated the severity of rat AIA, alongside reduced synovial proliferation, increased apoptosis, and decreased autophagy within AIA rat synovium. Moreover, Rapa co-treatment negated BSI's effects on synovial proliferation and apoptosis and abolished its anti-AIA activity.</div></div><div><h3>Conclusions</h3><div>BSI, as an AQP1 inhibitor, hindered AQP1-mediated autophagy, causing increased apoptosis, reduced proliferation in RA FLS, and relieved rat AIA symptoms.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156444"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075122","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}