Phytomedicine最新文献

{"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}

{"title":"Modulation of Pseudomonas aeruginosa-induced avoidance behavior by Shen Qi pills via mitogen-activated protein kinase PMK-1 and forkhead box protein O DAF-16 in Caenorhabditis elegans","authors":"Hanxiao Wang ,&nbsp;Siyi Lin ,&nbsp;Yingying Xu ,&nbsp;Huangjie Fu ,&nbsp;Meiqi Shen ,&nbsp;Ping Qiu ,&nbsp;Changyu Li ,&nbsp;Thomas Efferth ,&nbsp;Chunlan Hong","doi":"10.1016/j.phymed.2025.156585","DOIUrl":"10.1016/j.phymed.2025.156585","url":null,"abstract":"<div><h3>Background</h3><div>Avoidance behavior is one of the core features of anxiety and related in-depth study can help to reveal the biological basis of these disorders. In recent years, traditional Chinese medicine has incorporated <em>Shen Qi</em> pills to treat neuropsychiatric disorders, such as depression and post-traumatic stress, and has achieved significant therapeutic effects. However, its specific mechanism of action is still unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to link the avoidance phenotype to psychiatric disorders by utilizing the <em>Caenorhabditis elegans</em> as a biological model, revealing the potential common mechanisms underlying the treatment of these disorders with <em>Shen Qi</em> pills.</div></div><div><h3>Methods</h3><div>Avoidance behavior and immunity of <em>C. elegans</em> as a phenotypic entry point to explore the molecular mechanisms by which <em>Shen Qi</em> pills affects avoidance behavior with the help of <em>pmk-1</em> and <em>daf-16</em> mutants and RNA interference techniques.</div></div><div><h3>Results</h3><div>We found that the intervention of <em>Shen Qi</em> pills can delay the avoidance behavior of <em>C. elegans</em> to <em>P. aeruginosa</em>, improve the immunity level, and reduce the up-regulation of <em>pmk-1</em> and <em>daf-16</em> genes induced by <em>P. aeruginosa. Shen Qi</em> pills did not improve the immunity of <em>pmk-1</em> mutant but could still enhance the immunity of <em>daf-16</em> mutant. After daf-16 knockout, <em>Shen Qi</em> pills could not delay its avoidance behavior, which was consistent with the results shown in the neuron-specific silencing of <em>daf-16 C. elegans</em>.</div></div><div><h3>Conclusion</h3><div>These findings reveal the conclusion that <em>Shen Qi</em> pills regulate the avoidance behavior of <em>C. elegans</em> induced by <em>P. aeruginosa</em> via PMK-1 and DAF-16, with the latter acting directly on neurons independent of immune pathways.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156585"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549435","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":"Unveiling the role of mast cells in breast cancer–a case study of natural product Eriocalyxin B as an inhibitor","authors":"Leilei Gou ,&nbsp;Grace Gar-Lee Yue ,&nbsp;Ben Chung-Lap Chan ,&nbsp;Alaster Hang-Yung Lau ,&nbsp;Pema Tenzin Puno ,&nbsp;Clara Bik-San Lau","doi":"10.1016/j.phymed.2025.156596","DOIUrl":"10.1016/j.phymed.2025.156596","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation and breast cancer are closely associated. Considering that mast cells are essential component of inflammatory cells, its relationship with breast cancer arose rising attention.</div></div><div><h3>Purpose</h3><div>This study aims to elucidate the influence of mast cells on triple negative breast cancer (TNBC) and explore potential therapeutic interventions targeting mast cells.</div></div><div><h3>Methods</h3><div>The study employed proteomic analysis and molecular investigations to examine disparities between mast cells from healthy mice and those from breast tumor-bearing mice. Additionally, the natural product Ericalyxin B (Eri B) was utilized for its anti-inflammatory and anti-breast cancer properties. <em>Ex vivo</em> and <em>in vivo</em> treatments of Eri B were conducted to assess its impact on mast cell-mediated promotion of breast cancer.</div></div><div><h3>Results</h3><div>The crosstalk between mast cells and TNBC cells was found to enhance proliferation, invasion, and migration of TNBC cells. Mast cells from breast tumor-bearing mice exhibited disparities compared to those from healthy mice, as confirmed by proteomic analysis. Treatment with Eri B suppressed the promoting effect of mast cells on breast cancer by inhibiting the TAK1/NF-κB signaling pathway and downregulating downstream cytokine release. <em>In vivo</em> treatment with Eri B also reduced mast cell numbers and tryptase levels in tumors.</div></div><div><h3>Conclusion</h3><div>This is the first study to compare disparities between mast cells derived from healthy mice and those from breast tumor-bearing mice, while also revealing the effects of the natural product Eri B on mast cells in breast cancer. Our findings highlighted the crucial role of mast cells as potential targets for triple negative breast cancer therapy and suggests that Eri B holds promise in suppressing breast cancer progression by regulating mast cells.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156596"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550272","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":"Liensinine overcomes EGFR-TKI resistance in lung adenocarcinoma through DRP1-mediated autophagy","authors":"Yuling Chen ,&nbsp;Chenying Shu ,&nbsp;Zhaowei Yan ,&nbsp;Saiqun Zhang ,&nbsp;Weijie Zhang ,&nbsp;Jian Zhao ,&nbsp;Anqi Wang ,&nbsp;Jianjun Li ,&nbsp;Yuanyuan Zeng ,&nbsp;Jianjie Zhu ,&nbsp;Jian-an Huang ,&nbsp;Zeyi Liu","doi":"10.1016/j.phymed.2025.156593","DOIUrl":"10.1016/j.phymed.2025.156593","url":null,"abstract":"<div><h3>Introduction</h3><div>Persistent upregulation of autophagy contributes to tumour cells’ resistance to EGFR-TKI therapy, and hence, inhibiting autophagy could be a valuable strategy for overcoming such resistance.</div></div><div><h3>Objectives</h3><div>This study investigated the effects of liensinine in EGFR-TKI resistant lung adenocarcinoma (LUAD) and to explore the underlying mechanism.</div></div><div><h3>Methods</h3><div>CCK-8 assay, colony formation, EdU assay and apoptosis assays were conducted for investigating the effect of EGFR-TKI and liensinine combination treatment in LUAD. Furthermore, autophagic flux were detected by western blot, fluorescence assays and TEM. In addition, by employing a DARTS approach, a CETSA assay, and SPR analysis, we identified DRP1 as a target of liensinine. Finally, by establishing a xenograft model of the disease, the impact of combination treatment <em>in vivo</em> was assessed.</div></div><div><h3>Result</h3><div><em>In vitro</em> and <em>in vivo</em> experiments revealed that the novel autophagy inhibitor liensinine enhanced the sensitivity of LUAD to EGFR-TKIs. This effect was achieved by inhibiting autophagic flux. We then examined whether liensinine inhibits autophagic flux through the impairment of autophagosome and autolysosome degradation. Furthermore, we identified DRP1 as a target of liensinine. The activation of DRP1 by liensinine through dephosphorylation at Ser637 promotes the accumulation of autophagosomes and autolysosomes while simultaneously blocking autophagic flux, thereby enhancing the cancer cell-killing effects of EGFR-TKIs.</div></div><div><h3>Conclusions</h3><div>Our study validated the efficacy of liensinine in overcoming EGFR-TKI resistance and elucidated the mechanism underlying liensinine's inhibition of autophagy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156593"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550273","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":"Edaravone dexborneol exerts anti-epileptic effects on rodent temporal lobe epilepsy by promoting NMDAR deactivation and inhibiting oxidative stress","authors":"Wanhua Qiu ,&nbsp;Roumeng Chen ,&nbsp;Lechen Pan ,&nbsp;Yiqian Li ,&nbsp;Yuchen Xu ,&nbsp;Yuqian Li ,&nbsp;Ang Guo ,&nbsp;Wenting Huang ,&nbsp;Tao Tan ,&nbsp;Peijun Li ,&nbsp;Chenglong Xie ,&nbsp;Huiqin Xu ,&nbsp;Li Lin ,&nbsp;Xinshi Wang","doi":"10.1016/j.phymed.2025.156558","DOIUrl":"10.1016/j.phymed.2025.156558","url":null,"abstract":"<div><h3>Background</h3><div>Disease-modifying treatments with anti-epileptic effects are currently unavailable and urgently required for temporal lobe epilepsy (TLE). Combined therapy targeting multiple mechanisms may offer a promising anti-epileptic strategy, given the complex processes underlying epileptogenesis.</div></div><div><h3>Purpose</h3><div>This study evaluates the effects of Edaravone Dexbroneol, a combination of Edaravone and Dexborneol in 4:1, on rat and mouse TLE models and an in vitro epileptiform activity model.</div></div><div><h3>Methods</h3><div>The Pilocarpine-induced rat TLE model and the Kainic acid-induced mouse TLE model were used to assess the in vivo effect of Edaravone and/or Dexbornel. Primary neurons were utilized to evaluate the in vitro effect of drugs using calcium imaging, electrophysiological and biochemical analyses, as well as RNA sequencing.</div></div><div><h3>Results</h3><div>Treatment of Edaravone Dexbornel during the latent period significantly alleviated epileptic seizures in rodents, mitigated cognitive impairment, and inhibited neuronal loss and astrocytic activation. In vitro, Edaravone Dexborneol inhibited the action potentials and protected primary hippocampal neurons from Mg²⁺-free-induced neurite injury. All these effects were significantly more pronounced in the group treated with the Edaravone Dexborneol mixture compared to either drug used individually. Furthermore, Edaravone can significantly inhibit Mg²⁺-free-induced calcium oscillations in primary neurons, probably by promoting the deactivation of NMDA receptors. RNA sequencing and RT-PCR analysis revealed that synergetic regulation of lipid metabolism, oxidative stress, apoptosis, and calcium signaling probably underlay the neuroprotective effect of Edaravone Dexbornel on epileptic neurons.</div></div><div><h3>Conclusion</h3><div>Edaravone Dexborneol exhibits antiepileptic effects and may fill the gap in disease-modifying treatments for TLE.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156558"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550270","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":"Ginseng in delaying brain aging: Progress and Perspectives","authors":"Jingwen Niu ,&nbsp;Guoqi Zhu ,&nbsp;Junjie Zhang","doi":"10.1016/j.phymed.2025.156587","DOIUrl":"10.1016/j.phymed.2025.156587","url":null,"abstract":"<div><h3>Background</h3><div>The <em>Shennong Bencao Jing</em> (Shennong's Classic of Materia Medica) records that <em>Panax ginseng</em> C. A. Mey (ginseng) ‘lightens the body and prolongs life’. Many investigations have documented that ginseng exerts neuroprotective effects by mitigating the aging of the brain. However, a comprehensive review of the impacts of ginseng on brain aging remains lacking.</div></div><div><h3>Purpose</h3><div>This study aims to review the advances in ginseng research regarding its role in delaying brain aging, focusing on its bioactive constituents, underlying mechanisms and potential side effects. The findings provide scientific pieces of evidence to support the medical utilization of ginseng in the delaying senescence and the management of aging-related diseases.</div></div><div><h3>Methods</h3><div>This review includes studies on ginseng and brain aging in humans, retrieved from English-language research articles published between 2017 and the present in the PubMed and Web of Science databases. The work focused on ginseng, brain aging, and aging-related diseases, utilizing keywords such as “Ginseng”, “Brain aging”, “central nervous system”, “intracellular homeostasis”, “peripheral system”, <em>etc</em>.</div></div><div><h3>Results</h3><div>Ginseng comprises a varied spectrum of biologically bioactive constituents, such as ginsenosides, Maillard reaction products, ginseng polysaccharides, volatile oils, amino acids, proteins, <em>etc</em>. These components work to contribute to their significant medicinal value. Based on the traditional Chinese medicine (TCM) theory that “the heart and brain are interconnected, the liver and brain are mutually supportive, the brain and spleen are related, the brain and lung are linked, and the brain and kidney work in harmony,” we summarize that ginseng may sustain neural homeostasis through both central and peripheral perspectives. Additionally, the potential toxic side effects of ginseng are minimal.</div></div><div><h3>Conclusion</h3><div>Ginseng and its bioactive constituents exhibit considerable promise in delaying brain aging and treating neurodegenerative diseases. Future research should prioritize exploring the direct targets of ginseng and its active ingredients, and work toward establishing precise drug-target-efficacy relationships. This approach will facilitate the translation of these findings into clinically viable therapeutic approaches.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156587"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549432","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":"13-Methylpalmatine alleviates bleomycin-induced pulmonary fibrosis by suppressing the ITGA5/TGF-β/Smad signaling pathway","authors":"Qin Mao ,&nbsp;Jiajing Liu ,&nbsp;Yu Yan ,&nbsp;Gang Wang ,&nbsp;Miao Zhang ,&nbsp;Zhuo Wang ,&nbsp;Xiaowei Wen ,&nbsp;Zefeng Jiang ,&nbsp;Haijing Li ,&nbsp;Jing Li ,&nbsp;Mingyang Xu ,&nbsp;Rong Zhang ,&nbsp;Baofeng Yang","doi":"10.1016/j.phymed.2025.156545","DOIUrl":"10.1016/j.phymed.2025.156545","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease for which there is a lack of effective and safe therapeutic drugs. 13-Methylpalmatine (13-Me-PLT) is an active compound from <em>Coptis chinensis</em>, and no study has yet been reported on its pharmacological effects in pulmonary fibrotic diseases. The group has previously demonstrated the antimyocardial fibrosis efficacy of 13-Me-PLT but its effect on pulmonary fibrosis and its potential mechanism has not yet been investigated.</div></div><div><h3>Purpose</h3><div>The present research is designed to clarify the therapeutic potential and mechanism of action of 13-Me-PLT in IPF using a bleomycin (BLM)-induced mouse model of IPF.</div></div><div><h3>Methods</h3><div><em>In vivo</em>, mice were administrated with BLM to establish the IPF model, and IPF mice were treated with 13-Me-PLT (5, 10, and 20 mg/kg) and pirfenidone (PFD, 300 mg/kg) by gavage. <em>In vitro</em>, we employed TGF-β1 (10 ng/ml)-induced MRC5 cells, which were then treated with 13-Me-PLT (5, 10, 20 μM) and PFD (500 μM). High-throughput transcriptome sequencing, molecular dynamics simulations, molecular docking and Surface plasmon resonance (SPR) were employed to elucidate the underlying mechanisms of 13-Me-PLT in mitigating IPF.</div></div><div><h3>Result</h3><div><em>In vivo</em> experiments showed that 13-Me-PLT significantly ameliorated BLM-induced lung fibrosis in mice. <em>In vitro</em> studies, 13-Me-PLT showed good antifibrotic potential by inhibiting fibroblast differentiation. Transcriptomic analysis of mouse lung tissues identified ITGA5 and TGF-β/Smad signaling pathways as key targets for the antifibrotic effects of 13-Me-PLT. Molecular docking and kinetic analyses further supported these findings. Functional studies involving ITGA5 silencing and overexpression confirmed that 13-Me-PLT down-regulated ITGA5 expression and inhibited the activation of the TGF-β/Smad signaling pathway, confirming its mechanism of action.</div></div><div><h3>Conclusion</h3><div>To our best knowledge, these results provide the first insight that 13-Me-PLT is protective against BLM-induced IPF in mice. Unlike existing antifibrotic drugs, 13-Me-PLT specifically targets the ITGA5/TGF-β/Smad signaling pathway, offering a novel and potentially more effective therapeutic approach. This study not only validates the antifibrotic efficacy of 13-Me-PLT but also elucidates its unique mechanism of action, these findings may provide an opportunity to develop new drugs to treat IPF.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156545"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin ameliorates inflamed ulcerative colitis by regulating mast cell degranulation via the PAMP-MRGPRX2 feedback loop","authors":"Yihan Huang ,&nbsp;Na Wang ,&nbsp;Xiaolan Ji ,&nbsp;Shiqiong Luo ,&nbsp;Ling Gong ,&nbsp;Chenrui Zhao ,&nbsp;Guodong Zheng ,&nbsp;Rui Liu ,&nbsp;Tao Zhang","doi":"10.1016/j.phymed.2025.156564","DOIUrl":"10.1016/j.phymed.2025.156564","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study was to investigate the therapeutic effect of API on UC via the regulation of PAMP-MRGPRX2-mediated mast cells (MCs) degranulation.</div></div><div><h3>Background</h3><div>The pro-inflammatory positive feedback loop mediated by Mas-related G-protein-coupled receptor X2 (MRGPRX2) and its endogenous ligand, PAMP-12, is associated with ulcerative colitis (UC) progression. However, the therapeutic strategies that target MRGPRX2 in the treatment of UC are less reported. Apigenin (API), a natural flavonoid, can relieve inflammation.</div></div><div><h3>Method</h3><div>A dextran sodium sulfate (DSS)-induced mouse UC model was used to elucidate the therapeutic effects of API. Animal behavior assessment, serological assays, and histological analysis were performed in wild-type (WT) and MC MrgprB2-conditional knockout (CKO) mouse model. mRNA sequencing analysis, PCR, ELISA, and western blotting were performed <em>in vitro</em> and <em>in vivo</em> to elucidate the mechanism underlying the effect of API by a PAMP-12 triggered MC degranulation model.</div></div><div><h3>Results</h3><div>MC degranulation via MrgprB2 was critical for the persistence of inflammation in colitis. API attenuated colonic tissue damage, splenomegaly, and myeloperoxidase (MPO) activity in the colonic tissues. It also ameliorated colonic crypt structure damage and inflammatory cell infiltration. Moreover, API suppressed MCs degranulation, and the level of carboxypeptidases A3 (CPA3), in DSS-induced colitis, thereby blocking the pro-inflammatory positive feedback loop induced by PAMP-MrgprB2. Lastly, API effectively inhibited PAMP-12-triggered mast cell degranulation by regulating Akt1/XBP-1S/CHOP/TXNIP and NF-κB/IL-1β signaling pathways.</div></div><div><h3>Conclusion</h3><div>API alleviates inflammatory symptoms in UC by suppressing PAMP-MRGPRX2/B2 mediated MC sustained degranulation feedback loop.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156564"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549533","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}