Phytomedicine最新文献

{"title":"Liang-Ge-San attenuates virus-induced acute lung injury by targeting FXR-mediated ACE2 downregulation to modulate the formation of the cytokine storm","authors":"Liling Yang ,&nbsp;Xiangjun Zhou ,&nbsp;Junshan Liu ,&nbsp;Guangli Yang ,&nbsp;Jingtao Yu ,&nbsp;Weifu Tan ,&nbsp;Xiaochuan Fang ,&nbsp;Wei Li ,&nbsp;Jiayang He ,&nbsp;Qinhai Ma ,&nbsp;Linzhong Yu ,&nbsp;Zibin Lu","doi":"10.1016/j.phymed.2025.156584","DOIUrl":"10.1016/j.phymed.2025.156584","url":null,"abstract":"<div><h3>Background</h3><div>Traditional Chinese medicine has been recognized for its significant role in treating acute lung injury (ALI) due to its distinct therapeutic advantages. Liang-Ge-San (LGS), a formulation from the ancient “Taiping Huimin Hejiju Fang”, is believed to possess beneficial effects for treating ALI. However, LGS's precise mechanisms and efficacy in addressing viral ALI remain inadequately explored.</div></div><div><h3>Purpose</h3><div>To evaluate LGS's therapeutic effects and underlying mechanisms in treating viral-induced ALI.</div></div><div><h3>Methods</h3><div>The protective effects of LGS were examined in a Polyinosinic-polycytidylic acid [Poly(I:C)]-induced ALI model using real-time quantitative PCR, enzyme-linked immunosorbent assay, and histopathological analysis. A bioinformatics approach combined with network pharmacology was utilized to ascertain the key targets of LGS in viral pneumonia. The pharmacodynamic mechanisms of LGS in viral ALI were further validated through immunofluorescence, overexpression, short hairpin RNA, chromatin immunoprecipitation, and target agonist assays.</div></div><div><h3>Results</h3><div>LGS administration resulted in a reduction of IL-1β, IL-6, and TNF-α levels, along with a decrease in macrophage infiltration, pulmonary damage, and pneumonedema following the Poly(I:C) challenge. Bioinformatics and network pharmacology analyses suggested that Farnesyl X receptor (FXR) and angiotensin converting enzyme 2 (ACE2) are potential therapeutic targets for LGS in viral pneumonia. Further experiments revealed that LGS suppressed the expression of FXR, ACE2, and NF-κB-p65 in Poly(I:C)-infected cells. Notably, overexpression of FXR counteracted the repressive effects of LGS, while ACE2 expression remained unchanged in FXR-knockdown RAW264.7 cells upon treatment with Poly(I:C) or LGS. Additionally, LGS inhibited the interaction between FXR and ACE2 transcriptional promoters. <em>In vivo</em>, LGS attenuated the Poly(I:C)-induced upregulation of FXR, ACE2, IL-1β, IL-6, and TNF-α in ALI zebrafish and mice models, effects that could be reversed by chenodeoxycholic acid (CDCA), an FXR agonist. Moreover, LGS markedly alleviated weight loss, improved survival rates, reduced lung index, diminished viral load, and inhibited lung pathological changes in H1N1-PR8-induced ALI mice. IL-1β, IL-6, TNF-α, INF-γ, FXR, ACE2, small heterodimer partner, and NF-κB-p65 levels were markedly reduced by LGS, with these effects being reversed by CDCA.</div></div><div><h3>Conclusion</h3><div>This investigation provides the first evidence that FXR/ACE2 signaling is pivotal in acute respiratory viral infections, while LGS demonstrates antiviral activity against viral-induced ALI. LGS inhibits ACE2 expression induced by viral infection via FXR inhibition and modulates the cytokine storm, thus alleviating viral ALI. These findings suggest that LGS may be a promising treatment strategy for treating viral ALI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156584"},"PeriodicalIF":6.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578311","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":"Toosendanin-induced liver damage through irreparable DNA damage and autophagy flow blockade","authors":"Yifan Lin ,&nbsp;Jian Zhang ,&nbsp;Xinyue Gao ,&nbsp;Zekai Wu ,&nbsp;Lele Yang ,&nbsp;Kun Tian ,&nbsp;Xiaoqi Lv ,&nbsp;Jiaqi Li ,&nbsp;Kunqi Chen ,&nbsp;Youbo Zhang ,&nbsp;Hong Hu ,&nbsp;An Zhu","doi":"10.1016/j.phymed.2025.156586","DOIUrl":"10.1016/j.phymed.2025.156586","url":null,"abstract":"<div><h3>Objective</h3><div>The fruit of <em>Melia toosendan</em> Sieb. et Zucc<em>.</em> (MT) is known for its efficacy in relieving pain and treating roundworms. Toosendanin (TO) has been identified as a bioactive marker of MT, with hepatotoxic properties. This study offers a comprehensive investigation into the toxic mechanisms, involving TO-induced remaining DNA damage, cell cycle arrest, and the synergistic effect of autophagy flow disruption. It provides new insights into the clinical applications of MT and TO.</div></div><div><h3>Methods</h3><div>TO was prepared at 50, 100, and 200 μM for a 48 h treatment of HepG2 cells, while zebrafish were administered at 50, 75, and 100 μM for 72 h. Transcriptomics and computational molecular simulations, including network pharmacology, molecular docking, and molecular dynamics simulation, were used for target prediction. Fluorescent probes, flow cytometry, quantitative real-time polymerase chain reaction, and western blotting were employed for mechanism verification.</div></div><div><h3>Results</h3><div>TO disrupted the balance between reactive oxygen species and cellular antioxidant defense, resulting in mitochondrial damage and repression of DNA-dependent protein kinase catalytic subunit. This led to the inability to repair DNA damage and caused cell cycle arrest in the G1/S phase. As shown in computational molecular simulations and transcriptomics analysis, the repression of damaged organelle removal through autophagy flow disruption resulted in excessive injury and hepatocyte death.</div></div><div><h3>Conclusion</h3><div>By impairing DNA damage responses (DDRs) and autophagy, TO causes unrepaired DNA damage, which disrupts cell cycle progression through complex interactions with cyclin proteins and tumour suppressor genes, ultimately contributing to hepatotoxicity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156586"},"PeriodicalIF":6.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549528","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":"Ginsenoside CK inhibits EMT and overcomes oxaliplatin resistance in gastric cancer by targeting the PI3K/Akt pathway","authors":"Li Zhang,&nbsp;Xiao-Lan Zhao,&nbsp;Zhang-Jing Cao,&nbsp;Ke-Di Li,&nbsp;Li-Yue Xu,&nbsp;Fei Tang,&nbsp;Jing-Nan Zhang,&nbsp;Cheng Peng,&nbsp;Hui Ao","doi":"10.1016/j.phymed.2025.156516","DOIUrl":"10.1016/j.phymed.2025.156516","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer remains a leading cause of cancer mortality, with oxaliplatin (L-OHP) resistance posing a major therapeutic challenge. Ginsenosides have shown potential in addressing chemoresistance.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate whether ginsenoside Compound K (CK), a derivative of protopanaxadiol ginsenosides, could overcome L-OHP resistance in gastric cancer cells.</div></div><div><h3>Methods</h3><div>The anti-cancer effects of CK were investigated using L-OHP-resistant HGC27/L cells through comprehensive in vitro experiments. Cell viability, migration, invasion, apoptosis, and colony formation were evaluated under CK treatment alone or combined with L-OHP. Drug efflux was specifically assessed using Rhodamine 123 staining. To understand the molecular mechanism, network pharmacology and molecular docking analyses were employed, which identified the PI3K/Akt pathway as a crucial target of CK. This finding was further validated through Western blotting and RT-qPCR analyses, focusing on PI3K/Akt signaling components and EMT markers. Finally, drug-resistant gastric cancer xenograft models were established to evaluate the therapeutic efficacy of CK alone and in combination with L-OHP in vivo.</div></div><div><h3>Results</h3><div>CK effectively suppressed cell viability, migration, invasion, drug efflux, and colony formation while enhancing apoptosis in resistant cells. Mechanistically, CK inhibited the PI3K/Akt pathway, leading to reduced P-glycoprotein (P-gp) expression and EMT reversal. These effects were confirmed using PI3K pathway modulators. In xenograft models, CK significantly inhibited tumor growth and reduced PI3K/Akt activity, P-gp expression, and EMT markers.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that CK overcomes L-OHP resistance through PI3K/Akt pathway inhibition and EMT prevention, suggesting that combining CK with L-OHP may improve outcomes in chemoresistant gastric cancer patients.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156516"},"PeriodicalIF":6.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563526","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":"Huoxue Tongluo tablet enhances atherosclerosis efferocytosis by promoting the differentiation of Trem2+ macrophages via PPARγ signaling pathway","authors":"Xingling He ,&nbsp;Ziru Li ,&nbsp;Sijing Li ,&nbsp;Xiaojiao Zhang ,&nbsp;Donghua Liu ,&nbsp;Xiaowei Han ,&nbsp;Huan He ,&nbsp;Jiahui Chen ,&nbsp;Xiaoming Dong ,&nbsp;Wenjie Long ,&nbsp;Huan Lu ,&nbsp;Taochun Ye ,&nbsp;Fanhang Meng ,&nbsp;Huili Liao ,&nbsp;Zhongqi Yang ,&nbsp;Lu Lu ,&nbsp;Shihao Ni","doi":"10.1016/j.phymed.2025.156579","DOIUrl":"10.1016/j.phymed.2025.156579","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Atherosclerosis (AS) serves as the primary pathological basis for various cardiovascular and cerebrovascular diseases. Impaired efferocytosis by macrophages within AS plaques exacerbates lipid metabolism disorders and inflammatory responses. Huoxue Tongluo Tablet (HXTL), a traditional Chinese medicine formula, has shown efficacy in treating AS and modulating macrophage function. However, its underlying mechanisms remain unclear. It is hypothesized that HXTL ameliorates AS by enhancing macrophage efferocytosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To assess the efficacy and mechanisms of HXTL in treating AS at the single-cell level.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used to analyze the constituents of HXTL. HXTL was administered to ApoE⁻/⁻ mice maintained on a high-fat diet. The progression of AS was evaluated by measuring atherosclerotic plaque area, necrotic core formation, collagen depletion, lipid accumulation, lipid profiles, pro-inflammatory mediators, and oxidative stress markers. Transcriptomic analysis was performed to explore the mechanisms underlying the therapeutic effects of HXTL on AS. Efferocytosis-related marker expression was evaluated using immunohistochemistry and quantitative PCR (qPCR), and the efferocytosis index was determined by the co-localization of apoptotic cells and macrophages. Efferocytosis inhibition was induced using Cytochalasin D. Single-cell sequencing was utilized to investigate alterations in Trem2⁺ macrophages following HXTL treatment. Trem2 expression was accessed by immunohistochemistry and qPCR, while flow cytometry and immunofluorescence staining confirmed the changes in Trem2⁺ macrophages. Bioinformatic analyses were conducted to investigate the mechanism through which HXTL enhances efferocytosis by regulating Trem2⁺ macrophage subsets. Western blotting and qPCR were used to assess the expression levels of PPARγ signaling, and the regulatory role of PPARγ signaling in macrophage subpopulation generation and efferocytosis function was accessed using GW9662.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;UPLC-MS/MS analysis identified 99 major components in HXTL. In vivo, medium and high doses of HXTL significantly reduced atherosclerotic plaque area, improved lipid profiles, decreased pro-inflammatory mediators and reactive oxygen species (ROS), and enhanced the efferocytosis function. Inhibition of efferocytosis reversed these beneficial effects. Single-cell sequencing and in vivo validation revealed that HXTL upregulated Trem2⁺ macrophages and efferocytosis-related genes. Bioinformatics and in vivo experiments demonstrated that HXTL activated PPARγ signaling, and inhibition of PPARγ signaling negated the pro-efferocytosis effects and the upregulation of Trem2⁺ macrophage upregulation induced by HXTL.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;HXTL activates the PPARγ pathway, upregulates Trem2⁺ macrophage","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156579"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578323","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":"Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner","authors":"Xuheng Tang ,&nbsp;Lin Huang ,&nbsp;Weiquan Ma ,&nbsp;Mingxin Huang ,&nbsp;Zhenhua Zeng ,&nbsp;Yiqin Yu ,&nbsp;Na Qin ,&nbsp;Fei Zhou ,&nbsp;Fen Li ,&nbsp;Shenhai Gong ,&nbsp;Hong Yang","doi":"10.1016/j.phymed.2025.156580","DOIUrl":"10.1016/j.phymed.2025.156580","url":null,"abstract":"<div><h3>Background</h3><div>traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's “second brain,” regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.</div></div><div><h3>Purpose</h3><div>to investigate the effect of gut microbiota and metabolites disorder on TBI injury.</div></div><div><h3>Study design</h3><div>16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.</div></div><div><h3>Methods</h3><div>fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.</div></div><div><h3>Result</h3><div>rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.</div></div><div><h3>Conclusion</h3><div>our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156580"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578753","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":"Fangchinoline suppresses nasopharyngeal carcinoma progression by inhibiting SQLE to regulate the PI3K/AKT pathway dysregulation","authors":"Jieyun Xie ,&nbsp;Zexian Shi ,&nbsp;Lingling Sun ,&nbsp;Yihong Wu ,&nbsp;Jiuhuan Feng ,&nbsp;Han Wang ,&nbsp;Haifeng Lai","doi":"10.1016/j.phymed.2025.156484","DOIUrl":"10.1016/j.phymed.2025.156484","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, remains underexplored in nasopharyngeal carcinoma (NPC). Additionally, the therapeutic potential of Fangchinoline, an alkaloid with anticancer properties, has yet to be systematically evaluated. This research investigates Fangchinoline's efficacy in NPC treatment and SQLE-related mechanisms.</div></div><div><h3>Methods</h3><div>Drug screening in NPC cell lines C666–1 and 5–8F identified potential candidates. IC50 values were determined using CCK-8 assays, and apoptosis, proliferation, and invasion were assessed via Annexin V/PI staining, EdU staining, and Transwell assays. Cholesterol levels were quantified using a TG kit. RNA sequencing with GO/KEGG analyses identified key pathways. Correlation analysis was performed via cBioPortal and GEPIA2 databases, protein interaction networks via STRING and Cytoscape, and survival analysis via Kaplan-Meier curves. Gene and protein expression were validated with qPCR and Western blot, and an NPC mouse model confirmed in vivo efficacy.</div></div><div><h3>Results</h3><div>Fangchinoline inhibited NPC cell proliferation, induced apoptosis, and reduced cholesterol accumulation. RNA sequencing revealed that Fangchinoline downregulated SQLE expression, suppressing the PI3K/AKT pathway. Correlation and protein interaction analyses highlighted SQLE's role in NPC progression, and survival analysis confirmed its clinical relevance. By targeting SQLE and disrupting cholesterol metabolism, Fangchinoline suppressed tumor growth both in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that Fangchinoline inhibits NPC growth by targeting SQLE and disrupting the PI3K/AKT pathway, providing new insights into SQLE as a therapeutic target in NPC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156484"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628022","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":"Morus alba L. alleviates influenza viral pneumonia. Evidences of its mechanism of action","authors":"Junsong Jing ,&nbsp;Yi Sun ,&nbsp;Yiyang Shui ,&nbsp;Junyi Wang ,&nbsp;Wenjing Ye ,&nbsp;Ranran Chen ,&nbsp;Lianhao Wu ,&nbsp;Lijuan Xing ,&nbsp;Rongrong Huang ,&nbsp;Ting Zhou ,&nbsp;Wenwen Zhu ,&nbsp;Yueguo Wu ,&nbsp;Sheng Zhang ,&nbsp;Jing Shi ,&nbsp;Yuanyuan Li ,&nbsp;Yan Liu ,&nbsp;Zhenqiang You","doi":"10.1016/j.phymed.2025.156574","DOIUrl":"10.1016/j.phymed.2025.156574","url":null,"abstract":"<div><h3>Background</h3><div>Viral pneumonia is an infection of the lungs caused by numerous different viruses, which can lead to severe respiratory distress and even life-threatening conditions. In the absence of specific treatments for viral pneumonia, natural traditional medicines offer an alternative in terms of innovative drug therapies. <em>Morus alba L.</em> (common name mulberry leaf) is a Chinese medicine that has been used clinically as an antiviral.</div></div><div><h3>Purpose</h3><div>The therapeutic effect of <em>M. alba</em> on viral pneumonia was investigated along with its mechanism of action.</div></div><div><h3>Methods</h3><div>Network pharmacology and molecular docking were used to analyze the mechanism of action of <em>M. alba</em> in the treatment of viral pneumonia. Histology, immunofluorescence, Western blotting, qPCR, and flow cytometry were used to evaluate the protective effect of MLE (the ethanol extract of <em>Morus alba L.</em>) on PR8 (A/Puerto Rico/8/1934 H1N1, a murine lung-adapted influenza A virus strain)-induced viral pneumonia. SiRNA was used to validate the relationship between the therapeutic effects of MLE on viral pneumonia and the target Syk (a crucial non-receptor tyrosine kinase).</div></div><div><h3>Results</h3><div>MLE alleviated PR8-induced viral pneumonia by reducing inflammatory factor expression in the lungs, decreasing NF-κB pathway activation, slowing oxidative damage in the lungs, and inhibiting lung tissue cell apoptosis. Meanwhile, MLE for viral pneumonia was significantly associated with Syk targets. Notably, knockdown of the Syk gene not only reduced the therapeutic effect of MLE, but also suppressed PR8-induced viral pneumonia.</div></div><div><h3>Conclusion</h3><div>MLE can alleviate PR8-induced viral pneumonia through inhibiting the Dectin-1/Syk pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156574"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549537","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":"Procyanidins inhibit alphacoronavirus infection by reducing interferon antagonism","authors":"Yi Liu ,&nbsp;Xue Wang ,&nbsp;Xuefei Wang ,&nbsp;Wensai Mao ,&nbsp;Yujing Weng ,&nbsp;Yiqing Zhao ,&nbsp;Cong Duan ,&nbsp;Jiufeng Wang","doi":"10.1016/j.phymed.2025.156549","DOIUrl":"10.1016/j.phymed.2025.156549","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The development of coronavirus drugs has primarily focused on targeting viral components, such as RNA-dependent RNA polymerase (RdRP), with relatively little attention given to enhancing host antiviral defenses. α-Coronaviruses, including human-infecting HCoV-NL63 and HCoV-229E, utilize immune evasion strategies such as suppressing host interferon production to establish infection. Procyanidins (PC), oligomeric compounds composed of catechin and epicatechin, have demonstrated the ability to stimulate host interferon synthesis, potentially counteracting this immune evasion. Exploring the inhibitory effects of PC specifically on α-coronaviruses offers a promising avenue for developing novel therapeutic strategies that bolster host immunity against these pathogens.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to evaluate the inhibitory effects of PC on α-coronaviruses using different cell models and investigate whether its antiviral activity is linked to enhanced interferon production. By examining PC's effects on selected α-coronaviruses, this research explores its potential as a therapeutic strategy against human-infecting HCoV-NL63 and HCoV-229E, which evade innate immunity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Vero cells, human embryonic kidney 293T (HEK-293T) cells, and intestinal porcine epithelial-J2 (IPEC-J2) cells were used as cell models, with porcine epidemic diarrhea virus (PEDV) serving as the α-coronavirus infection model. The inhibitory effects of PC on the α-coronaviruses and its activation of interferon were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB). Co-immunoprecipitation (co-IP) was used to assess how PC impacts the degradation of Retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1) by coronavirus N protein. Confocal microscopy was utilized to observe the recovery of mitochondrial morphology disrupted by coronavirus, and flow cytometry analyses were conducted.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Viral cycle and time-of-addition analyses showed that PC inhibited PEDV infection during both the replication and release stages of the virus. Simultaneously, in the early stages of infection, PC countered PEDV's evasion of interferon by elevating host interferon levels. Co-immunoprecipitation experiments confirmed that this effect was achieved by reducing the binding of coronavirus N protein to key proteins in the interferon synthesis pathway, RIG-I and TBK1, a mechanism previously identified as one of the main reasons for interferon evasion by α-coronavirus N protein. Additionally, intriguingly, we observed that PC has the ability to restore excessive mitochondrial fission induced by coronaviruses, an effect achieved by reducing the binding of coronavirus N protein to mitochondrial fusion protein 1 (MFN1). This observation suggests potential mechanistic pathways through which PC impacts mitochondrial antiviral-related proteins.","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156549"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520685","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":"Huangqi and Danshen improve the chronic nephrotoxicity of cyclosporin A by regulating lipid metabolism","authors":"Ran-ran Gao ,&nbsp;Cong Han ,&nbsp;Gui-yuan Sui ,&nbsp;Yi-bing Chen ,&nbsp;Le Zhou ,&nbsp;Hong-zhen Hu ,&nbsp;Yi-Chuan Wang ,&nbsp;Yao Liu ,&nbsp;Wei Li","doi":"10.1016/j.phymed.2025.156582","DOIUrl":"10.1016/j.phymed.2025.156582","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role in CsA nephrotoxicity is not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza Bunge) (HD) play roles in ameliorating the nephrotoxicity of CsA, but their mechanisms still need to be fully clarified.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study innovatively aimed to analyse the coexpression of renal proteins and serum metabolites for the identification of key pathways and targets. This study provides novel insight into the mechanism by which HD ameliorates CsA-induced nephrotoxicity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We utilized HD to intervene in both in vivo and in vitro nephrotoxicity models induced by CsA. For the in vivo experiments, we constructed a coexpression network of renal proteins and serum metabolites, which was used to screen for key pathways. To validate these findings, we knocked down key proteins in vivo. For the in vitro studies, we employed MTT, Transwell, flow cytometry, and immunofluorescence assays to monitor the epithelial–mesenchymal transition (EMT) of HK-2 cells. Additionally, we used electron microscopy and Seahorse assays to examine the effects of HD on mitochondrial structure and function. Furthermore, we overexpressed Ppara to further confirm the mechanism by which HD improves renal function.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;HD can improve renal pathological damage and function; regulate blood lipids, inflammation and oxidative stress indicators; and reduce apoptosis in renal tissues. Joint protein and metabolomics analyses revealed that two lipid metabolism-related pathways (the PPAR signalling pathway and linoleic acid metabolism pathway) were coenriched, involving six differential proteins (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, and Pck1) and two differentially abundant metabolites (alpha-Dimorphecolic acid and 12,13-EpOME). Western blot was used to verify differentially expressed proteins. HD improved mitochondrial damage and lipid accumulation, as demonstrated by transmission electron microscopy (TEM) analysis and Oil Red O staining. Knockdown of the key protein Ppara affected the expression of ACOX1 and exacerbated RF. In vitro verification demonstrated that HD significantly inhibited CsA-induced EMT in HK-2 cells and improved mitochondrial structure and function. Ppara overexpression promoted HD-mediated regulation of mitochondrial function, reduced apoptosis, and improved HK-2 RF.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;HD can ameliorate CsA nephrotoxicity through renal protein-serum metabolism coexpression, the PPAR signalling pathway, and linoleic acid metabolism. HD-induced upregulation of Ppara to regulate lipid metabolism, improve mitochondrial function and reduce apoptosis are important mechanisms. The Ppara/ACOX1/TGF-β1 axis may play an important role in this process. These ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156582"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578308","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":"Uncovering the underlying mechanism of yuanhuacine against colorectal cancer by transcriptomics and experimental investigations","authors":"Jingchu Li ,&nbsp;Shanshan Liu ,&nbsp;Jian Chen ,&nbsp;Hanxue Wang ,&nbsp;Xia Feng ,&nbsp;Chenglin Jia ,&nbsp;Jiacheng Li ,&nbsp;Hao Yin ,&nbsp;Jie Li ,&nbsp;Chang Liu ,&nbsp;Yongbing Cao ,&nbsp;Chao Ma","doi":"10.1016/j.phymed.2025.156570","DOIUrl":"10.1016/j.phymed.2025.156570","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) holds the third position in terms of incidence and ranks behind lung cancer in terms of mortality worldwide. Yuanhuacine, one of the main active ingredients of genkwa flos, has demonstrated promising application prospects in the field of cancer treatment. However, its underlying mechanism against CRC has not been fully clarified.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate anti-tumor activity of yuanhuacine and clarify its underlying mechanism in CRC.</div></div><div><h3>Methods</h3><div>CRC HCT116, HT-29, Caco-2, SW480, and LS174T cells were used to assess the <em>in vitro</em> anti-tumor activity of yuanhuacine by cell viability, proliferation, apoptosis, cycle distribution, migration, and colony formation assays. Meanwhile, an HT-29 xenograft mouse model was successfully constructed to investigate the anti-tumor effect of yuanhuacine <em>in vivo</em>. Transcriptomic assay and network pharmacology were applied to explore the underlying mechanism of yuanhuacine in combating CRC, which was further verified by quantitative reverse transcription polymerase chain reaction, western blot. The interaction of yuanhuacine with protein was performed by molecular docking, molecular dynamics simulation, and cell thermal shift assays.</div></div><div><h3>Results</h3><div>Yuanhuacine significantly induced apoptosis and reduced viability of CRC cells with IC₅₀ values ranging from 28.09 to 56.16 μM. Moreover, it suppressed the colony formation ability of CRC cells and inhibited the expression of proliferation marker Ki67 in CRC cells and tissues. Meanwhile, the impairment of cell migration by yuanhuacine has been identified by wound healing assay and transwell migration assay. Furthermore, cell cycle assay showed that yuanhuacine resulted in significant G2/M phase arrest. Yuanhuacine significantly inhibited the tumor growth of HT-29 xenograft mice without obvious pathological changes in major organs. Mechanistically, the differentially expressed genes were enriched in cell cycle by both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses. The mRNA and protein expressions of PLK1, CCNA2, and TTK were inhibited by yuanhuacine. Cell thermal shift assay further validated the direct interactions between yuanhuacine and each of PLK1, CCNA2, and TTK. The anti-proliferation activity and cell cycle arrest induced by yuanhuacine were reversed by overexpression of PLK1.</div></div><div><h3>Conclusions</h3><div>Yuanhuacine is a promising candidate compound in combating CRC by inhibiting proliferation of CRC cells. The major underlying mechanism involves regulating PLK1, which results in G2/M phase arrest.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156570"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520687","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}