PhytomedicinePub Date : 2025-06-14DOI: 10.1016/j.phymed.2025.156957
Delida Aidebaike , Hailong Gong , Yun Xia , Guoqing Jing , Huifan Liu , Huimin Zhou , Die Wu , Jing Zuo , Cheng Yang , Xing Wang , Yingyue Dong , Jie Yan , Xue Chen , Zihan Lei , Junjie Liang , Xiaojing Wu , Xuemin Song
{"title":"Tanshinone IIA attenuates sepsis-induced lung injury by reducing VEGFR2/PI3K/AKT-driven mitochondrial disruption dependent apoptosis","authors":"Delida Aidebaike , Hailong Gong , Yun Xia , Guoqing Jing , Huifan Liu , Huimin Zhou , Die Wu , Jing Zuo , Cheng Yang , Xing Wang , Yingyue Dong , Jie Yan , Xue Chen , Zihan Lei , Junjie Liang , Xiaojing Wu , Xuemin Song","doi":"10.1016/j.phymed.2025.156957","DOIUrl":"10.1016/j.phymed.2025.156957","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced lung injury (SILI) is marked by excessive inflammation and apoptosis, posing considerable therapeutic problems owing to the scarcity of targeted therapy. Tanshinone IIA (TanIIA), a bioactive molecule extracted from <em>Salvia miltiorrhiza</em>, demonstrates potential in regulating inflammatory pathways and enhancing cellular resilience.</div></div><div><h3>Purpose</h3><div>This study comprehensively examined the therapeutic mechanisms of TanIIA in SILI by an integrated methodology that incorporates network pharmacology, molecular docking, and comprehensive experimental validation.</div></div><div><h3>Methods</h3><div>Network pharmacology and WGCNA analysis of GSE239388 revealed possible treatment targets for TanIIA. Computational analysis utilizing molecular docking techniques and molecular dynamics simulations validated a stable intermolecular connection between TanIIA and the vascular endothelial growth factor receptor 2.</div><div>TanIIA's therapeutic effectiveness was evaluated in vivo using septic mouse model. BEAS-2B cells treated with LPS in vitro were employed to elucidate the underlying mechanisms. Western blotting, qRT-PCR, immunohistochemistry, flow cytometry, and mitochondrial function assays were performed to evaluate gene expression, apoptosis, and mitochondrial functionality.</div></div><div><h3>Results</h3><div>VEGFR2 was identified as a critical therapeutic target of TanIIA in SILI. Treatment with TanIIA significantly enhanced survival rates, mitigated lung histopathological damage, and decreased levels of pro-inflammatory cytokines in CLP-induced septic mice. Mechanistically, TanIIA suppressed the VEGFR2-PI3K-AKT signaling pathway, preserving mitochondrial integrity and inhibiting apoptosis. Additional validation was obtained using LPS-treated BEAS-2B epithelial cells, reinforcing the initial findings.</div></div><div><h3>Conclusion</h3><div>TanIIA provides protective effects against SILI by specifically targeting VEGFR2 and inhibiting the PI3K/AKT signaling pathway, which helps maintain mitochondrial homeostasis and reduces apoptosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156957"},"PeriodicalIF":6.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329753","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}
PhytomedicinePub Date : 2025-06-13DOI: 10.1016/j.phymed.2025.156934
Bao-xin Zheng , Yan Yi , Xing-wen Wang , Chun-ying Li , Yong Zhao , Jing-zhuo Tian , Lian-mei Wang , Jia-yin Han , Chen Pan , Su-yan Liu , Chen-yue Liu , Sha-Sha Qin , Xuan Tang , Mei-ting Liu , Ai-hua Liang
{"title":"Corrigendum to “Geniposide via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-κB, and promoting TGR5 inhibition of NLRP3 inflammasome” [Phytomedicine, 142 (2025), 156791]","authors":"Bao-xin Zheng , Yan Yi , Xing-wen Wang , Chun-ying Li , Yong Zhao , Jing-zhuo Tian , Lian-mei Wang , Jia-yin Han , Chen Pan , Su-yan Liu , Chen-yue Liu , Sha-Sha Qin , Xuan Tang , Mei-ting Liu , Ai-hua Liang","doi":"10.1016/j.phymed.2025.156934","DOIUrl":"10.1016/j.phymed.2025.156934","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156934"},"PeriodicalIF":6.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294805","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}
PhytomedicinePub Date : 2025-06-13DOI: 10.1016/j.phymed.2025.156980
Yang Liao , Xian Xiao , Wen Cheng , Yiyuan Wang , Jiayan Lu , Jingtao Zhang , Jiaqi Zhang , Peiyu Liu , Liang Liu , Hudan Pan
{"title":"Natural products in rheumatoid arthritis: Cell type-specific mechanisms and therapeutic implications","authors":"Yang Liao , Xian Xiao , Wen Cheng , Yiyuan Wang , Jiayan Lu , Jingtao Zhang , Jiaqi Zhang , Peiyu Liu , Liang Liu , Hudan Pan","doi":"10.1016/j.phymed.2025.156980","DOIUrl":"10.1016/j.phymed.2025.156980","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of rheumatoid arthritis (RA) involves abnormal activation and interactions among various cell types. Traditional Chinese medicine (TCM) natural products show therapeutic potential with multi-target anti-inflammatory effects, but their specific impacts on RA-related cell types remain unclear.</div></div><div><h3>Purpose</h3><div>This review aims to provide a comprehensive overview of the effects of natural products on key cell types in RA.</div></div><div><h3>Methods</h3><div>We extensively searched PubMed, Web of Science, and Scopus until April 2025, using keywords like \"natural products,\" \"rheumatoid arthritis,\" \"cellular mechanisms,\" and specific cell types. Studies on natural products' effects on RA-related cells were included and analyzed.</div></div><div><h3>Results</h3><div>This review marks the first attempt to integrate cellular resolution in evaluating therapeutic mechanisms of natural products in RA. The key findings highlight the cell-type-specific effects and mechanistic underpinnings of natural products. Sinomenine preferentially inhibits fibroblast-like synoviocytes (FLS) proliferation via toll-like receptor 4 (TLR4) /MyD88/NF-κB blockade, whereas icariin reprograms macrophage polarization through ERK/HIF-1α/GLUT1 signaling pathway. Besides, natural products exhibit shared mechanisms across different cell types, such as oxidative stress and inflammatory pathway regulation. Importantly, certain natural products exhibit pan-cellular effects, targeting multiple cell types involved in RA pathogenesis. For example, resveratrol acts on a wide range of cell types including FLS, human umbilical vein endothelial cells (HUVECs), T cells, osteoclasts, chondrocytes, macrophages, monocytes, osteoblasts, and neutrophils.</div></div><div><h3>Conclusions</h3><div>Through an in-depth analysis of cellular mechanisms, this work highlights the specific regulatory effects of natural products on key cell types and their extensive influence across cellular networks. By examining these effects at the cellular level, this review establishes a new framework for developing novel RA therapeutics with increased cell selectivity, thus advancing precision phytomedicine and translational research.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156980"},"PeriodicalIF":6.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321600","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}
PhytomedicinePub Date : 2025-06-12DOI: 10.1016/j.phymed.2025.156962
Ling-Ling Wu , Weihua Di , Litao Shao , Jie Zhou , Yu-Yu Qiu , Mengrui Zhang , Zhenye Li , Yanqun Zhang , Pengcheng Luan , Jifan Li , Gongchang Yu , Guiqian Fang , Caicai Meng , Bin Shi , Xuemei Zhao , Qixin Chen , Xintian Shao
{"title":"Subcellular redistribution of Rhein from whole cellular to single mitochondria for enhancing anti-hepatoma efficacy","authors":"Ling-Ling Wu , Weihua Di , Litao Shao , Jie Zhou , Yu-Yu Qiu , Mengrui Zhang , Zhenye Li , Yanqun Zhang , Pengcheng Luan , Jifan Li , Gongchang Yu , Guiqian Fang , Caicai Meng , Bin Shi , Xuemei Zhao , Qixin Chen , Xintian Shao","doi":"10.1016/j.phymed.2025.156962","DOIUrl":"10.1016/j.phymed.2025.156962","url":null,"abstract":"<div><h3>Background</h3><div>RECQL4 is a critical factor in DNA repair and serves as a significant biomarker for liver cancer. Inhibiting RECQL4 induces apoptosis in liver cancer cells. Given the role of mitochondria in regulating apoptosis and the dual localization of RECQL4 in both the mitochondria and nucleus, targeting mitochondrial RECQL4 may induce mitochondrial dysfunction, thereby enhancing the therapeutic efficacy of liver cancer treatments.</div></div><div><h3>Purpose</h3><div>Unlike traditional drug structure optimization, which focuses solely on protein target interactions, our approach optimizes drug structure based on both organelle distribution and protein interactions.</div></div><div><h3>Methods</h3><div>As a proof of concept, we selected Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), an auto-fluorescent, lipophilic anthraquinone found in a variety of different medicinal herbs used in TCM that is known to bind to RECQL4, a protein that is distributed throughout the cytosol, mitochondria, and other subcellular locations, albeit unevenly. Rhein has the tendency to accumulate in different subcellular organelles, which reduces the overall efficacy of the drug. To overcome this limitation, we conjugated a triphenylphosphonium group Rhein to direct the drug to the mitochondria, resulting in <strong>Rh-Mito</strong>.</div></div><div><h3>Results</h3><div>Our results demonstrated that this chemical modification retains the ability to intervene in the expression of RECQL4 protein while also improving the cellular uptake of <strong>Rh-Mito</strong>. Utilizing advanced imaging techniques, we show that <strong>Rh-Mito</strong> preferentially accumulated in the mitochondria, where it targeted RECQL4 to inhibit the repair of mtDNA, altered the morphology of mitochondrial cristae, and induced apoptosis. Notably, <strong>Rh-Mito</strong> displayed superior anti-tumor efficacy compared to unmodified Rhein.</div></div><div><h3>Conclusion</h3><div><strong>Rh-Mito</strong> was designed to selectively target mitochondria, avoiding interactions with other organelles. This modification strengthens its binding to RECQL4, disrupts mitochondrial cristae, inhibits tumor cell migration, and promotes apoptosis, thereby improving its therapeutic efficacy in liver cancer treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156962"},"PeriodicalIF":6.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338622","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}
PhytomedicinePub Date : 2025-06-12DOI: 10.1016/j.phymed.2025.156981
Hongyu Li , Wenkai Chen , Xiangchen Zeng , Ronghai He, Guangrong Ji
{"title":"Quinacrine induces autophagy via the Dlg5/AKT pathway to inhibit osteosarcoma cell proliferation and suppresses migration and invasion through the Dlg5/Girdin pathway","authors":"Hongyu Li , Wenkai Chen , Xiangchen Zeng , Ronghai He, Guangrong Ji","doi":"10.1016/j.phymed.2025.156981","DOIUrl":"10.1016/j.phymed.2025.156981","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is a malignant tumor of bone that originates from mesenchymal cells. Although improvements have been made in the survival rate of five years, the outlook for individuals with metastatic or recurrent disease remains unfavorable, highlighting the need for new therapeutic strategies and drug candidates. Quinacrine (QC) is a plant-derived bioactive compound extracted from the bark of the cinchona tree, has shown promising anticancer properties by suppressing the proliferation of cancer cells, inducing autophagy, and overcoming resistance to treatment. However, its potential therapeutic application in OS has yet to be thoroughly investigated.</div></div><div><h3>Purpose</h3><div>In this study, we investigated the inhibitory effects of QC, a plant-derived bioactive compound extracted from the bark of the cinchona tree, on the proliferation and migration of osteosarcoma cells and its potential mechanisms.</div></div><div><h3>Methods</h3><div>This study comprehensively evaluated the impact of QC on OS cells using both in vitro and in vivo models. Specific molecular pathways of OS cell growth inhibition by Quinacrine revealed by RNA-seq analysis. The inhibitory effect of QC on tumor growth and its potential organ toxicity were systematically investigated by constructing an in vivo mouse tumor model.</div></div><div><h3>Results</h3><div>The outcomes suggested that QC notably suppressed the growth, migration, and invasion of 143B and MG63 OS cells, causing the arrest of the cell cycle at the G2/M checkpoint. RNA sequencing analysis showed that QC inhibited AKT phosphorylation and induced autophagy in OS cells by increasing the expression of the Dlg5 gene. Furthermore, silencing the Dlg5 gene promoted OS cell proliferation and reduced the inhibitory effect of QC, thereby confirming the importance of Dlg5 in mediating its effects. This study also validated the molecular pathway by which QC inhibits OS cell migration and invasion by modulating the Dlg5/Girdin signaling pathway. In vivo, QC treatment led to a significant decrease in tumor growth in mice, with no evident organ toxicity observed.</div></div><div><h3>Conclusion</h3><div>In summary, QC suppresses the OS cells' growth by regulating the Dlg5/AKT signaling pathway and suppresses migration and invasion through the Dlg5/Girdin Pathway, emphasizing its potential as a therapeutic agent for OS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156981"},"PeriodicalIF":6.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322076","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}
PhytomedicinePub Date : 2025-06-12DOI: 10.1016/j.phymed.2025.156965
Yuchan Li , Liang Ye , Shixin Li , Bing Yang , Jian Li , Xiaobin Jia , Liang Feng
{"title":"Ranunculus ternatus Thunb. alkaloids attenuate colorectal cancer metastasis through EMT suppression","authors":"Yuchan Li , Liang Ye , Shixin Li , Bing Yang , Jian Li , Xiaobin Jia , Liang Feng","doi":"10.1016/j.phymed.2025.156965","DOIUrl":"10.1016/j.phymed.2025.156965","url":null,"abstract":"<div><h3>Background</h3><div>Distant metastasis remains a major contributor to treatment failure and poor prognosis in colorectal cancer (CRC), emphasizing the urgent need for novel anti-metastatic strategies. Ranunculus ternatus Thunb. (RT), a traditional herbal medicine historically used to treat tuberculosis, has recently shown emerging potential in oncology. However, its efficacy against CRC metastasis remains uninvestigated, and the pharmacologically active components along with the underlying mechanisms responsible for its anti-CRC and metastasis-inhibitory effects are yet to be elucidated.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the anti-metastatic efficacy of bioactive components derived from RT and elucidate their mechanisms of action against CRC.</div></div><div><h3>Methods</h3><div>The active fraction of RT was identified using HCT116 and CT26 cell lines, alongside ectopic tumor-bearing mouse models. The chemical composition of this fraction was characterized by UPLC-Q-TOF/MS analysis. Transcriptomics profiling integrated with KEGG pathway enrichment analysis was performed, followed by core target prediction using CytoHubba and MCODE algorithms. RT-PCR, ELISA and Western Blot assays were employed for target validation. Drug-target interactions were confirmed via the cellular thermal shift assay (CETSA). The anti-metastatic effects of RT alkaloids (RTAs) were further evaluated through Transwell invasion assays, wound healing experiments, and tail vein injection-induced metastatic murine models.</div></div><div><h3>Results</h3><div>Both in vivo and in vitro experiments revealed that alkaloids from RT (RTAs) are the principal active ingredients exerting anti-CRC effects. Transcriptomic profiling and bioinformatics analyses demonstrate that RTAs inhibit epithelial-mesenchymal transition (EMT), with MMP3 and CCL5 identified as critical targets. Validation assays confirmed that RTAs significantly reduced levels of TGF-β and CCL5 in tumor tissues and serum of CRC-bearing mice. In addition, RTAs downregulated MMP3, MMP9, and β-catenin, while upregulating E-cadherin expression. These findings suggest that RTAs inhibit metastasis by modulating multiple EMT-related pathways. Furthermore, both in vitro and in vivo assays confirmed the ability of RTAs to significantly suppress distant metastasis in CRC models.</div></div><div><h3>Conclusion</h3><div>This study provides the first experimental evidence that RT exerts anti-metastatic effects against CRC. The bioactive alkaloid fraction (RTAs) mitigates CRC progression and metastasis by regulating the EMT process, highlighting its potential as a promising therapeutic candidate for metastatic CRC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156965"},"PeriodicalIF":6.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321602","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}
PhytomedicinePub Date : 2025-06-12DOI: 10.1016/j.phymed.2025.156966
Yuqin Peng , Hao Sun , Fan Xu , Haiyong Ye , Yan Wang , Xian Zhou , Dennis Chang , Ning Wang , Ping Huang
{"title":"Activation of BDNF-TrkB-PI3K-AKT signaling pathway by Tong-Qiao-Huo-Xue Decoction facilitates nerve regeneration and mitigates cerebral ischemia-reperfusion injury","authors":"Yuqin Peng , Hao Sun , Fan Xu , Haiyong Ye , Yan Wang , Xian Zhou , Dennis Chang , Ning Wang , Ping Huang","doi":"10.1016/j.phymed.2025.156966","DOIUrl":"10.1016/j.phymed.2025.156966","url":null,"abstract":"<div><h3>Background</h3><div>Nerve regeneration is an important manifestation of self-repair mechanism after stroke. Tong-Qiao-Huo-Xue Decoction (TQHXD) has significant neuroprotective effects, but whether this effect is related to promoting nerve regeneration remains to be further explored.</div></div><div><h3>Objective</h3><div>To investigate the mechanisms underlying anti-cerebral ischemia-reperfusion injury and elucidate the reparative mechanism of TQHXD in ischemic stroke injury.</div></div><div><h3>Methods</h3><div>Model of middle cerebral artery obstruction(MCAO/R) in rats induced cerebral ischemia injury and then reperfusion was established using the thread embolus method, and cell model of oxygen glucose deprivation followed by glucose reoxygenation(OGD/R)injury was established in vitro to simulate cerebral ischemia reperfusion injury (CI/RI). The cerebral blood flow of rats was detected through the use of super-resolution blood flow meter and laser speckle, and the chemical components of TQHXD were analyzed using UPLC-Q-TOF/MS. The rats' learning and memory abilities were assessed through water maze and field experiments. The proliferation and differentiation of neural stem cells (NSCs) were assessed using flow cytometry, transwell migration assay, and scratch wound healing assay. Molecular docking probed into the binding affinity between the chemical components of TQHXD and BDNF. Pull-down experiments were conducted to validate the interaction between TrkB and PI3K.</div></div><div><h3>Result</h3><div>TQHXD demonstrates significant reduction in cerebral infarction volume in rats with an ischemia-reperfusion injury model, alleviates pathological brain tissue damage, improves rat learning and memory abilities, promotes NSCs proliferation and differentiation, up-regulates the expression of Nestin, PCNA, NeuN and DCX proteins in vivo and in vitro, as well as increases nerve ball diameter. It also mitigated OGD/R-induced NSCs injury under BDNF knockdown conditions.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that TQHXD promotes the proliferation and differentiation of endogenous NSCs by activating the BDNF/TrkB/PI3K/AKT signaling pathway, which may serve as a potential therapeutic target for functional recovery after stroke.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156966"},"PeriodicalIF":6.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489551","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":"Protective effects of pollenin B in asthma: PPAR-γ-mediated regulation of inflammatory pathways and arachidonic acid metabolism","authors":"Yuanyuan Wu , Mengnan Zeng , Xinmian Jiao , Xinyi Ma , Haoyu Wang , Yanling Chen , Xiaoke Zheng , Weisheng Feng","doi":"10.1016/j.phymed.2025.156975","DOIUrl":"10.1016/j.phymed.2025.156975","url":null,"abstract":"<div><h3>Background</h3><div>Asthma poses a significant global health challenge, characterized by increasing prevalence and treatment complexities. Although <em>Ephedrae Herba</em> has long been used in asthma therapy, its pharmacological basis and mechanism of action remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to clarify the protective effects of pollenin B (PolB), a compound extracted from <em>Ephedrae Herba</em>, in asthmatic mice and to thoroughly explore its possible action pathways and molecular mechanisms. This study supplements pharmacological research on the anti-asthmatic effects of <em>Ephedrae Herba</em> and provides more information for the development of novel and highly effective drugs for the treatment of asthma.</div></div><div><h3>Methods</h3><div>An ovalbumin (OVA)-induced asthma model was used to evaluate the effects of PolB on asthma symptoms and lung histopathology. Furthermore, cytokine profiles in the serum and bronchoalveolar lavage fluid (BALF), immune cell populations, and serum metabolomics data were analyzed to identify the pathways involved in PolB activity. PPAR-<em>γ</em> was identified as a key target, and its interaction with PolB was confirmed by surface plasmon resonance (SPR) analysis. A PPAR-<em>γ</em> inhibitor (T0070907) was administered in vivo, and combined PPAR-<em>γ</em> agonist (rosiglitazone)/inhibitor (T0070907) assays were conducted in vitro to validate the mechanisms involved.</div></div><div><h3>Results</h3><div>PolB improved asthma symptoms, modulated cytokine levels in the serum and BALF, modulated immune cells, and influenced arachidonic acid metabolism. Further mechanistic exploration indicated that PolB mitigated airway inflammation by regulating arachidonic acid metabolism and the JAK-STAT pathway via PPAR-<em>γ</em>.</div></div><div><h3>Conclusion</h3><div>PolB exerts anti-asthmatic effects via PPAR-<em>γ</em>-mediated regulation of key pathways. These findings not only enrich modern pharmacological research on the anti-asthmatic properties of <em>Ephedrae Herba</em> but also deepen our understanding of asthma pathogenesis, thus providing new insights into the optimization of asthma prevention and treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156975"},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329752","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}
PhytomedicinePub Date : 2025-06-11DOI: 10.1016/j.phymed.2025.156972
Ruipeng Shi , Sio I Chan , Haochun Jin , Wei Li , Lili Zhang , Jinglin Yang , Ruichen Wang , Xiaoting Zheng , Guozhen Cui , Zhangfeng Zhong
{"title":"Jiegeng Gancao Decoction Ameliorates Ulcerative Colitis: An Integrative Approach Combining Network Pharmacology and Proteomics via in silico and in vivo studies","authors":"Ruipeng Shi , Sio I Chan , Haochun Jin , Wei Li , Lili Zhang , Jinglin Yang , Ruichen Wang , Xiaoting Zheng , Guozhen Cui , Zhangfeng Zhong","doi":"10.1016/j.phymed.2025.156972","DOIUrl":"10.1016/j.phymed.2025.156972","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that significantly affects the quality of life of patients. Although current treatments offer some relief, they are often accompanied by side effects and limited long-term efficacy. <em>Jiegeng Gancao</em> Decoction (JGD), a Chinese classical prescription composed of Platycodon and Licorice, are potential alternative treatments with minimal side effects.</div></div><div><h3>Purpose</h3><div>This present study aimed to establish a novel strategy for herbal medicine research, using JGD as a case study to improve the prediction efficiency and accuracy of network pharmacology and leveraging big data to accelerate herbal medicine research and development.</div></div><div><h3>Study design</h3><div>Given the unmet clinical needs in the treatment of UC and the promising potential of JGD, this study integrated chemical profiling, network pharmacology predictions, and proteomic analysis to establish a model to explore the therapeutic mechanisms of JGD for the treatment of UC.</div></div><div><h3>Methods</h3><div>UHPLC-Q-Exactive Orbitrap/MS was used to analyze the chemical components of JGD and its serum metabolites. Big data and network pharmacology were used to predict targets and pathways. A mouse model of DSS-induced colitis was established and were administered by JGD orally at 1.85 mg/kg daily. Therapeutic outcomes were evaluated through colon length detection, body weight monitoring, Disease Activity Index (DAI) scoring, and histopathological assessments. Enzyme-linked immunosorbent assay (ELISA), proteomics, flow cytometry, and western blotting were used to explore the underlying mechanism of the anti-colitis effects of JGD.</div></div><div><h3>Results</h3><div>The chemical composition of JGD was analyzed to identify key bioactive compounds using UHPLC-Q-Exactive Orbitrap/MS. These compounds were evaluated using big data and network pharmacology, incorporating four data sources. Compounds were sourced from Herb: 102, Serum: 21, Review: 117, and Database: 99. This integration generated 72 combos and 864 datasets related to the Gene, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. JGD treatment significantly attenuated DSS-induced colitis in mice by improving body weight, colon length, inflammatory response, and intestinal barrier. Furthermore, proteomics and western blotting experiments confirmed that JGD attenuated DSS-induced down-regulated protein levels of SLC6A14 and RAGE. By screening the components of JGD via docking with RAGE and SLC6A14, Glycyrrhetic acid 3-O-glucuronide, Kaempferol-3-O-rutinoside, and Glyasperin A were identified as the main pharmacological substances that underlie the anti-colitis effects of JGD.</div></div><div><h3>Conclusion</h3><div>Combining data from herb extracts and sources from the literature significantly improved prediction efficiency and accuracy. The results highlight the thera","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156972"},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329676","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}