Phytomedicine最新文献

{"title":"Xiaochaihutang ameliorates depression-like behaviors induced via chronic social defeat stress by regulating exon-specific Bdnf transcription through H3K18 acetylation in the hippocampus of mice","authors":"Fan Wang,&nbsp;Ziming Li,&nbsp;Boru Li,&nbsp;Meijing Xu,&nbsp;Yu Wang,&nbsp;Jiaying Wang,&nbsp;Jinlai Li,&nbsp;Yuwei Zhu,&nbsp;Linqi He,&nbsp;Jianchi Ma,&nbsp;Lin Mao,&nbsp;Xixi Xu,&nbsp;Xinwei Li,&nbsp;Haotian Zhang,&nbsp;Jingyu Yang,&nbsp;Kuo Zhang,&nbsp;Chunfu Wu","doi":"10.1016/j.phymed.2025.156567","DOIUrl":"10.1016/j.phymed.2025.156567","url":null,"abstract":"<div><h3>Introduction</h3><div>Depression is a prevalent and persistent mental disease characterized by symptoms such as anhedonia, anxiety, and desperation. Although our previous study shows that Xiaochaihutang (XCHT) upregulates hippocampal brain-derived neurotrophic factor (BDNF) levels in depressed mice and rats, the underlying mechanism requires further clarification.</div></div><div><h3>Objectives</h3><div>To assess the mechanism by which XCHT regulates hippocampal BDNF expression in chronic social defeat stress (CSDS)-induced mice.</div></div><div><h3>Methods</h3><div>Adult C57BL/6J mice were exposed to CSDS for 10 consecutive days to establish a depression model. XCHT treatment (2.3, 7 and 21 g/kg, intragastric administration) was administered for 4 consecutive weeks. Behavioral assessments were sequentially conducted to investigate the antidepressant effects of CSDS-induced XCHT. Golgi staining, immunofluorescence, immunoblotting, real time fluorescence quantitative polymerase chain reaction and chromatin immunoprecipitation were then employed to study the mechanisms underlying the regulation of XCHT on hippocampal BDNF expression.</div></div><div><h3>Results</h3><div>XCHT significantly improved CSDS-induced anhedonia, social avoidance, recognition memory impairment, and anxiety/depression-like behaviors in mice. XCHT significantly promoted neuronal complexity and dendritic spine maturation in the mouse hippocampus. Furthermore, XCHT reversed the CSDS-induced reduction in the number of hippocampal BDNF⁺ cells and increased hippocampal BDNF protein and mRNA levels by upregulating the expression of specific <em>Bdnf</em> exons I, IV and VI. XCHT increased <em>Bdnf</em> transcripts by upregulating histone H3K18 acetylation at the <em>Bdnf</em> promoters. The administration of an acetyltransferase inhibitor reversed the effects of these changes.</div></div><div><h3>Conclusion</h3><div>XCHT may enhance the transcripts of specific <em>Bdnf</em> exons I, VI and VI by upregulating the H3K18 acetylation at the corresponding <em>Bdnf</em> promoters, which consequently promotes BDNF expression levels. This further promotes neuronal plasticity in the hippocampus, ultimately ameliorating anxiety/depression-like behavior in CSDS-induced mice.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156567"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting GATA6 with pedunculoside inhibits fetal gene expression to attenuate pathological cardiac hypertrophy","authors":"An Pan ,&nbsp;Anqi Shi ,&nbsp;Huanhuan Chen,&nbsp;Lina Jiang,&nbsp;Qiang Zhang,&nbsp;Jiayi Feng,&nbsp;Jinting He,&nbsp;Jian Liu,&nbsp;Junwei Wang,&nbsp;Lihong Hu","doi":"10.1016/j.phymed.2025.156603","DOIUrl":"10.1016/j.phymed.2025.156603","url":null,"abstract":"<div><h3>Background</h3><div>Pathological cardiac hypertrophy is a characteristic feature of numerous cardiovascular diseases and significantly impacts human health. However, effective treatment options for cardiac hypertrophy are still significantly unmet. Pedunculoside, a pentacyclic triterpenoid saponin from the traditional Chinese herb <em>Ilex rotunda</em> Thunb., exhibits various pharmacological properties such as anti-inflammatory and cardiovascular therapeutic effects, but its anti-hypertrophy efficacy and mechanisms have not yet been reported.</div></div><div><h3>Purpose</h3><div>This study aimed to confirm the ameliorating effect of pedunculoside on cardiac hypertrophy and elucidate its underlying mechanism.</div></div><div><h3>Methods</h3><div>To investigate the effect of pedunculoside on cardiac hypertrophy, we used transverse aortic constriction (TAC) and isoproterenol hydrochloride (ISO) infusion to induce cardiac hypertrophy model in mice. Angiotensin II (Ang II) was used to mimic hypertrophy model in myocardial cells. Then, we utilized a biotin-tagged carabrone chemical probe and validation experiments to pinpoint pedunculoside's key targets. Further, molecular docking study and sites mutation were used to predict and identify the binding modes of pedunculoside to target. Finally, structural optimization was carried out to find new pedunculoside derivatives with stronger anti-hypertrophy activity and binding affinity to the target.</div></div><div><h3>Results</h3><div>Our findings revealed for the first time that pedunculoside treatment significantly attenuated hypertrophic phenotypes in response to TAC and ISO. It also effectively reduced hypertrophy and fibrosis in myocardial cells exposed to Ang II stimulation. Mechanically, we identified transcription factor GATA-6 (GATA6) as a key target of pedunculoside for treating cardiac hypertrophy. Further studies demonstrated that pedunculoside blocks cardiac hypertrophy progression by inhibiting the transcriptional activation of GATA6 on promoting fetal gene expression. More importantly, a new pedunculoside derivative <strong>PE-3</strong> with stronger anti-hypertrophy activity and affinity for GATA6 was discovered.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that pedunculoside and <strong>PE-3</strong> could be developed as promising drug candidates for cardiac hypertrophy treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156603"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549535","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":"Piperlongumine alleviates viral myocarditis by inhibiting pyroptosis through NF-κB pathway","authors":"Hui Li ,&nbsp;Min Wang ,&nbsp;Zhengdong Hua ,&nbsp;Hengzhong Guo ,&nbsp;Yuting Qiu ,&nbsp;Zhengyang Zhang ,&nbsp;Yu Zou ,&nbsp;Lili Lu","doi":"10.1016/j.phymed.2025.156606","DOIUrl":"10.1016/j.phymed.2025.156606","url":null,"abstract":"<div><h3>Background</h3><div>Viral myocarditis (VMC) is a cardiac condition characterized by inflammation of the myocardium due to viral infection. It is a significant cause of sudden cardiac death in young adults, and effective treatments remain limited. Inflammatory caspase-mediated pyroptosis serves as a host defense mechanism against pathogens and is crucial in the pathogenesis of VMC. Piperlongumine (PL), an amide alkaloid derived from <em>Piper longum</em> l., exhibits notable anti-inflammatory properties. However, there has been no reported research on the use of PL for the treatment of VMC.</div></div><div><h3>Purpose</h3><div>To explore the role of PL in inhibiting VMC by regulating cardiomyocyte pyroptosis and the potential molecular mechanism.</div></div><div><h3>Methods</h3><div>To evaluate the effect of PL on VMC, we established the VMC mouse model through intraperitoneal injection of coxsackie virus B3 (CVB3) for <em>in vivo</em> experiments. Subsequently, we assessed body weight, cardiac histopathological changes, cardiac function, and cardiomyocyte pyroptosis in VMC mice following PL treatment using hematoxylin and eosin (HE) staining, echocardiography, real-time quantitative PCR (RT-qPCR), and western blot analysis. The impact of PL on mouse cardiac muscle cell line (HL-1) pyroptosis was evaluated through the cell counting kit-8 assay kit (CCK8), RT-qPCR, immunofluorescence, and western blot. Additionally, network pharmacology was employed to preliminarily analyze the cellular pathways by which PL reduces VMC <em>via</em> the inhibition of pyroptosis, and the results of this analysis were validated through western blot.</div></div><div><h3>Results</h3><div><em>In vivo</em> experimental results demonstrated that following PL treatment, symptoms in VMC mice were significantly alleviated, cardiac function was restored, inflammation in cardiac tissue was reduced, and both myocardial cell pyroptosis and levels of inflammatory factors were notably decreased. Similar findings were observed <em>in vitro</em>. Network pharmacology analysis indicated that the NF-κB pathway may serve as a critical target for PL treatment of VMC. Furthermore, <em>in vitro</em> experiments revealed that the specific NF-κB pathway inhibitor MG132 can significantly inhibit CVB3-induced pyroptosis. Additionally, PL could reduce the phosphorylation levels of key molecules in the NF-κB signal pathway in a dose dependent manner.</div></div><div><h3>Conclusion</h3><div>In summary, this study presents evidence that PL ameliorates cardiomyocyte injury and enhances cardiac function in VMC mice, by reducing pyroptosis through the inhibition of the NF-κB pathway. These findings offer new insights for the potential of PL in VMC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156606"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563396","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":"A decade review on phytochemistry and pharmacological activities of Cynomorium songaricum Rupr.: Insights into metabolic syndrome","authors":"Zhihao Liu ,&nbsp;Qihao Li ,&nbsp;Fu Zhao ,&nbsp;Jihang Chen","doi":"10.1016/j.phymed.2025.156602","DOIUrl":"10.1016/j.phymed.2025.156602","url":null,"abstract":"<div><h3>Background</h3><div><em>Cynomorium songaricum</em> Rupr. (CSR), a perennial herb with a rich history in traditional medicine, has demonstrated therapeutic potential against metabolic syndrome (MetS) through its active compounds, including proanthocyanidins, polysaccharides, and triterpenoids. MetS, a global health concern, encompasses interlinked conditions such as obesity, type 2 diabetes mellitus (T2DM), and inflammation. This review synthesizes recent findings on CSR's pharmacological and phytochemical properties, focusing on its role in ameliorating MetS.</div></div><div><h3>Methods</h3><div>Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, relevant studies were retrieved from PubMed, Web of Science, and CNKI databases up to December 2024. Keywords included “<em>Cynomorium Songaricum</em> Rupr.”, “Cynomorii Herba”, “Suoyang”, “Suo Yang”, “Metabolic syndrome”, “Proanthocyanidins”, “Polysaccharides” and “Triterpenoids” and their combinations. Inclusion criteria emphasized studies exploring CSR's impact on MetS, while duplicate, low-quality studies and studies not written in Chinese, English, or unrelated were excluded.</div></div><div><h3>Results</h3><div>A total of 92 studies were analyzed, revealing that CSR's active components exhibit multi-target effects. Proanthocyanidins reduce glucose absorption and oxidative stress, polysaccharides enhance insulin sensitivity and gut microbiota composition, and triterpenoids mitigate obesity and mitochondria damage. These mechanisms collectively contribute to the beneficial effects of CSR against MetS.</div></div><div><h3>Conclusion</h3><div>CSR presents a promising natural therapy for MetS, utilizing its pharmacologically active compounds to address core metabolic dysfunctions. Future studies should focus on clinical validation and safety assessments to facilitate CSR's integration into modern therapeutic regimens.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156602"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578324","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":"Metabolism profiles of tannins in Phyllanthus emblica L. and its immunotherapeutic potential against hepatocellular carcinoma by re-educating tumor microenvironment","authors":"Zihao Chang ,&nbsp;Zhaohui Wang ,&nbsp;Yinxin Chen ,&nbsp;Yuqi Liu ,&nbsp;Ye Gao ,&nbsp;Yitong Cui ,&nbsp;Le Wang ,&nbsp;Yue Liu ,&nbsp;Ruiyang Cheng ,&nbsp;Runping Liu ,&nbsp;Lanzhen Zhang","doi":"10.1016/j.phymed.2025.156576","DOIUrl":"10.1016/j.phymed.2025.156576","url":null,"abstract":"<div><h3>Purpose</h3><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Tumor-associated macrophages (TAMs) are key components of the immunosuppressive tumor microenvironment and represent significant obstacles to effective immunotherapy. <em>Phyllanthus emblica</em> L. (PE), a medicinal plant traditionally used in Tibet, has shown therapeutic promise. This study investigates the effects of the tannin fraction of PE (PE-TF) on HCC and its ability to modulate the tumor immunosuppressive microenvironment.</div></div><div><h3>Methods</h3><div>We evaluated the antitumor efficacy of PE-TF using H22 xenografts and Hepa1–6 orthotopic mouse models. Transcriptomic analysis was performed to identify molecular targets underlying PE-TF suppression of HCC growth. Additionally, UPLC-MS/MS analysis identified the prototypic and metabolic components of PE-TF present in serum, tumor tissues, and adjacent normal liver tissues in the orthotopic HCC model.</div></div><div><h3>Results</h3><div>PE-TF significantly suppressed tumor growth in both subcutaneous and orthotopic HCC models and promoted reprogramming of TAMs toward an antitumor M1 phenotype in vivo. Furthermore, PE-TF counteracted the protumoral effects mediated by bone marrow-derived macrophages (BMDMs) exposed to Hepa1–6-derived conditioned medium (HCM). Although TBH promoted macrophage M2 polarization, the reactive oxygen species (ROS)-scavenging activity of PE-TF effectively inhibited this process. Modulation of the tumor microenvironment by PE-TF-enhanced CD8⁺ <em>T</em> cell infiltration and bolstered their antitumor response, as evidenced by increased transcription of perforin, IFN-γ, and IL-2. Transcriptomic analysis further revealed that T-cell receptor and cytotoxic T-cell signaling pathways are critical mediators of PE-TF’ therapeutic effects. Moreover, we preliminarily characterized 79 components across serum, liver, and tumor tissues, and identified metabolic pathways for PE-TF ingredients—including methylation and glycosylation modifications of tumor-enriched constituents. Notably, seven components, such as corilagin and urolithin D, are hypothesized to possess immunomodulatory properties.</div></div><div><h3>Conclusion</h3><div>Our findings underscore the potential of PE-TF as an adjuvant immunotherapy for HCC. By scavenging ROS, PE-TF reverses the immunosuppressive M2-TAM phenotype and remodels the tumor microenvironment, thereby enhancing antitumor immunity. Additionally, integrating chemical and metabolic profiling offers a promising strategy for refining candidate selection in future drug discovery endeavors.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156576"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609480","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":"Cirsium japonicum leaf extract attenuated lipopolysaccharide-induced acute respiratory distress syndrome in mice via suppression of the NLRP3 and HIF1α pathways","authors":"Eun Yeong Lim ,&nbsp;Gun-Dong Kim ,&nbsp;Ha-Jung Kim ,&nbsp;Ji-Eun Eom ,&nbsp;Hyeon-Ji Song ,&nbsp;Dong-Uk Shin ,&nbsp;Young In Kim ,&nbsp;Hyun-Jin Kim ,&nbsp;So-Young Lee ,&nbsp;Hee Soon Shin","doi":"10.1016/j.phymed.2025.156601","DOIUrl":"10.1016/j.phymed.2025.156601","url":null,"abstract":"<div><h3>Background</h3><div>Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, alveolar barrier dysfunction, edema, and dysregulated alveolar macrophage-mediated pulmonary inflammation. Despite advancements in treatment strategies, the mortality rate in patients with ARDS remains high, ranging from 40–60 %. Current approaches are limited to supportive care, necessitating the exploration of effective therapeutic options such as suppressing broad inflammatory responses. Although <em>Cirsium japonicum</em> leaves possess anti-inflammatory properties, their specific effects on ARDS have not yet been investigated.</div></div><div><h3>Methods</h3><div>The anti-inflammatory activity of <em>Cirsium japonicum</em> extract (CJE) was investigated in a lipopolysaccharide (LPS)-induced ARDS model.</div></div><div><h3>Results</h3><div>CJE significantly attenuated LPS-induced lung injury, including reduced alveolar wall thickness, inflammatory cell infiltration, proteinaceous debris, and hyaline membranes. Moreover, CJE repressed infiltration of inflammatory cells and pro-inflammatory gene expression in bronchoalveolar lavage fluid. Concordantly, CJE mitigated alveolar macrophage activation, which consequently reduced neutrophil chemoattractic infiltration. Additionally, CJE suppressed NLRP3 and HIF1α expression in the lungs of the ARDS mouse. Similarly, LPS-induced NLRP3 and HIF1α pathway-associated inflammatory and glycolytic gene expressions significantly diminished by CJE in murine alveolar macrophage cell line, MH-S cells, and bone marrow-derived macrophages.</div></div><div><h3>Conclusion</h3><div>CJE suppressed multiple inflammatory responses through the regulation of NLRP3 and HIF1α signaling-related gene expression in macrophages of LPS-induced ARDS mice. These results suggest that CJE has therapeutic potential for treating patients with ARDS via macrophage regulation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156601"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578756","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":"β-Ionone suppresses colorectal tumorigenesis by activating OR51E2, a potential tumor suppressor","authors":"Ji-Sun Kim ,&nbsp;Sungyun Cho ,&nbsp;Mi-Young Jeong ,&nbsp;Adriana Rivera-Piza ,&nbsp;Yeonji Kim ,&nbsp;Chunyan Wu ,&nbsp;Ye Eun Yoon ,&nbsp;InRyeong Lee ,&nbsp;Jung-Won Choi ,&nbsp;Ha Lim Lee ,&nbsp;Sung Won Shin ,&nbsp;Jaeeun Shin ,&nbsp;Hyeonmin Gil ,&nbsp;Min-Goo Lee ,&nbsp;NaNa Keum ,&nbsp;Jin-A Kim ,&nbsp;Dain Lee ,&nbsp;Yong Hun Jung ,&nbsp;Seok Chung ,&nbsp;Min-Jeong Shin ,&nbsp;Sung-Joon Lee","doi":"10.1016/j.phymed.2025.156599","DOIUrl":"10.1016/j.phymed.2025.156599","url":null,"abstract":"<div><h3>Background</h3><div>Olfactory receptors (ORs) are present in non-olfactory tissues and contribute to diverse biological roles beyond smell perception. Among them, OR51E2 has been associated with cancer biology, and its activator, β-ionone, a natural terpenoid, is known to have anticancer effects.</div></div><div><h3>Purpose</h3><div>This study aimed to clarify the tumor-suppressive role of OR51E2 in colorectal cancer (CRC), unravel the regulatory mechanism underlying its downregulation, and evaluate the therapeutic potential of β-ionone, an OR51E2 ligand, in CRC progression.</div></div><div><h3>Study design and methods</h3><div>OR51E2 expression was analyzed in human CRC tissues, matched adjacent normal tissues, and cell lines. The involvement of N⁶-methyladenosine (m⁶A) modification of <em>OR51E2</em> mRNA stability was examined using <em>METTL3/14</em> and <em>YTHDF1/2/3</em> knockdown experiments. β-Ionone-mediated effects on intracellular calcium signaling, cell proliferation, migration, and apoptosis were evaluated in an OR51E2-dependent manner. The therapeutic efficacy of β-ionone was further evaluated in vivo using a xenograft model in nude mice.</div></div><div><h3>Results</h3><div>OR51E2 mRNA expression and immunoreactivity were significantly reduced in CRC cells and tissues due to decreased mRNA stability. Knockdown of <em>METTL3/14</em> or <em>YTHDF1/2/3</em> increased OR51E2 mRNA and protein expression and inhibited CRC cell proliferation. Treatment with STM2457, an METTL3 inhibitor, restored OR51E2 expression and suppressed CRC cell proliferation. β-Ionone, a ligand of OR51E2, increased intracellular calcium levels, decreased MEK/ERK phosphorylation, and inhibited CRC cell proliferation while inducing apoptosis. These effects were abolished in OR51E2 knockdown cells. In a xenograft model, β-ionone administration (5 and 10 mg/kg body weight) significantly reduced tumor growth.</div></div><div><h3>Conclusion</h3><div>This study identifies m⁶A modification as a critical mechanism underlying the downregulation of OR51E2 in CRC. Activation of OR51E2 by β-ionone suppresses CRC cell proliferation and induces apoptosis by elevating intracellular calcium levels, which inhibits the MEK-ERK pathway. These findings highlight OR51E2 as a potential therapeutic target and suggest that β-ionone or m⁶A inhibition may represent novel strategies for CRC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156599"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628126","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":"Effective compound combination of Bufei Yishen formula ameliorates PM2.5-induced COPD by inhibiting mitochondrial oxidative stress through SIRT3-mediated FOXO3 deacetylation","authors":"Jing Wang ,&nbsp;Huiyu Yue ,&nbsp;Yangzi Dong ,&nbsp;Tiantian Liu ,&nbsp;Jiansheng Li","doi":"10.1016/j.phymed.2025.156568","DOIUrl":"10.1016/j.phymed.2025.156568","url":null,"abstract":"<div><h3>Background</h3><div>Fine particulate matter (PM2.5) exposure significantly contributes to the development of chronic obstructive pulmonary disease (COPD). However, the underlying mechanisms remain inadequately elucidated, and there is a lack of effective clinical treatments. A combination of five bioactive ingredients derived from the traditional Chinese prescription Bufei Yishen formula (BYF) that is widely accepted for COPD treatment, exhibits bioequivalence with BYF and has been shown to alleviate COPD exacerbation in rat models induced by PM2.5 exposure.</div></div><div><h3>Purpose</h3><div>To investigate the underlying mechanisms of the effective compound combination (ECC) attenuating mitochondrial oxidative stress in COPD progression induced by PM2.5 exposure.</div></div><div><h3>Methods</h3><div>The COPD rats were induced by cigarette smoke inhalation and bacterial infection, then exposed to real-time PM2.5 by a whole-body exposure system. The therapeutic efficacy of ECC was assessed by evaluating lung function, pathological changes, levels of oxidative stress, and inflammation. <em>In vitro</em>, the PM2.5-induced human bronchial and alveolar epithelial cells (BEAS-2B and HPAEpiC) were used to explore the underlying mechanisms of ECC against mitochondrial oxidative stress.</div></div><div><h3>Results</h3><div>Initially, based on the successful establishment of a PM2.5-aggravated COPD rat model, we demonstrated the protective effects of ECC on COPD progression induced by PM2.5 exposure by improving lung function, alleviating pathological injury, and reducing oxidative stress and inflammation. Subsequently, we identified that the inhibitory effects of ECC on mitochondrial oxidative damage, respiratory dysfunction, and fission/fusion imbalance induced by PM2.5 are primarily mediated through SIRT3 activation, both <em>in vivo</em> and <em>in vitro</em>. Mechanically, the deacetylation of FOXO3 at lysine residues 271 and 290 by SIRT3 is crucial for ECC to mitigate mitochondrial oxidative stress during the progression of COPD in response to PM2.5.</div></div><div><h3>Conclusion</h3><div>This study reveals a previously unrecognized mechanism by which ECC acts as an agonist of SIRT3, offering potential therapeutic benefits for patients with COPD who are exposed to PM2.5.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156568"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578310","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":"Poncirin ameliorates alcoholic liver injury by regulating lipid metabolism and inflammatory response in a PPARα dependent manner","authors":"Jiawen Huang ,&nbsp;Kaili Zhou ,&nbsp;Jiayu Li ,&nbsp;Zaibin Xu ,&nbsp;Xiaoqin Wu ,&nbsp;Tingting Chen ,&nbsp;Danna Wang ,&nbsp;Huafeng Pan ,&nbsp;Shuiqing Huang ,&nbsp;Tianwen Liu ,&nbsp;Zhuohui Luo ,&nbsp;Yong Gao","doi":"10.1016/j.phymed.2025.156598","DOIUrl":"10.1016/j.phymed.2025.156598","url":null,"abstract":"<div><h3>Background</h3><div>Poncirin (PO) is a citrus flavonoid with various of functional effect including cardiac ischemia-reperfusion injury, colitis, cancer, et al. Considering the role of PO in improving inflammation and lipid metabolism, it may have potential therapeutic effects on alcoholic liver injury (ALI), but there are currently no relevant reports.</div></div><div><h3>Purpose</h3><div>Current study aimed to explore the protective effect of PO on preventing ALI.</div></div><div><h3>Methods</h3><div>A chronic ethanol-fed mice was used as ALI-mice model and ethanol-induced mouse primary hepatocytes (MPHs) as ALI-cells model. Multiple molecular biology analysis methods are used to evaluate PO's efficacy.</div></div><div><h3>Results</h3><div>Both <em>in vivo</em> and <em>in vitro</em>, PO improved the inflammatory response and lipid deposition induced by ethanol. According to RNA-seq analysis, Peroxisome proliferator activated receptor alpha (PPARα) had been found as a potential target, followed by the experiment validation using Cellular Thermal Shift Assay (CETSA), Western bolt analysis as well as qPCR analysis. In addition, the protective effect of PO was reduced or disappeared in PPARα^-/- ALI mice, both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>This is the first study to evaluate the role of PO in preventing ALI by targeting lipid metabolism and the inflammatory response by partly targeting the PPARα pathway, providing a fundamental basis for the use of PO as a functional food to alleviate ALI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156598"},"PeriodicalIF":6.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578754","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":"Multimodal discovery of bavachinin A: A natural FLT3 agonist for treating thrombocytopenia","authors":"Long Wang ,&nbsp;Ting Zhang ,&nbsp;Xin Yang ,&nbsp;Qi Mo ,&nbsp;Mei Ran ,&nbsp;Rong Li ,&nbsp;Bo Yang ,&nbsp;Hongping Shen ,&nbsp;Qinyao Li ,&nbsp;Zhichao Li ,&nbsp;Nan Jiang ,&nbsp;Jing Zeng ,&nbsp;Xiang Xie ,&nbsp;Siyu He ,&nbsp;Feihong Huang ,&nbsp;Chunxiang Zhang ,&nbsp;Jiesi Luo ,&nbsp;Jianming Wu","doi":"10.1016/j.phymed.2025.156597","DOIUrl":"10.1016/j.phymed.2025.156597","url":null,"abstract":"<div><h3>Background</h3><div>Radiation-induced thrombocytopenia (RIT) poses a serious risk to patients with cancer undergoing radiotherapy and leads to hemorrhage and mortality. Unfortunately, effective treatment options for RIT are currently limited.</div></div><div><h3>Purpose</h3><div>This study aimed to discover active compound from Fructus Psoraleae, a traditional Chinese medicine recognized for its hemostatic properties, and to elucidate its mechanism of action in the treatment of RIT.</div></div><div><h3>Methods</h3><div>The efficacy of Fructus Psoraleae in treating thrombocytopenia was assessed using network pharmacology. A drug-screening model was built using a naive Bayes algorithm to determine the effective compounds in Fructus Psoraleae. Giemsa staining and flow cytometry were used to evaluate the effects of bavachinin A on megakaryocytes (MK) differentiation. RIT and thrombopoietin (TPO) receptor (c-MPL) knockout (c-MPL^−/−) mice were used to assess the therapeutic efficacy of bavachinin A in mitigating thrombocytopenia. Tg (cd41:eGFP) zebrafish were used to investigate the effect of bavachinin A on thrombopoiesis. RNA sequencing (RNA-seq), molecular docking simulations, molecular dynamics simulations, drug affinity responsive target stability assay (DARTS), and biolayer interferometry (BLI) were used to elucidate the molecular mechanisms of action of bavachinin A against thrombocytopenia.</div></div><div><h3>Results</h3><div><em>In silico</em> analysis using a drug screening model identified bavachinin A as promising candidate compound derived from Fructus Psoraleae. <em>In vitro</em> experiments demonstrated that Bavachinin A induced MK differentiation. <em>In vivo</em> experiments revealed that bavachinin A augmented platelet levels and improved coagulation in RIT mice, facilitated megakaryopoiesis and platelet levels in c-MPL^−/− mice, and accelerated thrombopoiesis in zebrafish. Furthermore, RNA-seq, molecular docking simulations, molecular dynamics simulations, DARTS, and BLI demonstrated that bavachinin A bound directly to fms-like tyrosine kinase 3 (FLT3). Notably, blocking FLT3 or phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway hindered bavachinin-A-induced MK differentiation. However, repressing the TPO/c-MPL signaling pathway had no significant effect.</div></div><div><h3>Conclusion</h3><div>Bavachinin A promotes MK differentiation and thrombopoiesis by directly binding to FLT3 and activating PI3K/Akt signaling. Importantly, this effect was not dependent on the conventional TPO/c-MPL signaling pathway. This study underscores the translational potential of bavachinin A as a promising novel therapeutic for thrombocytopenia, offering novel insights into TPO-independent mechanisms of thrombopoiesis and establishing a robust multimodal approach for drug discovery.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156597"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578309","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}