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Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-25 DOI: 10.1016/j.phymed.2025.156417
Chuyu Wang , Ying Zhao , Yingfei Peng , Wei Chen , Jie Zhu , Chenzheng Gu , Ran Huo , Lin Ding , Yu Liu , Te Liu , Chunyan Zhang , Wenjing Yang , Hao Wang , Wei Guo , Beili Wang
{"title":"Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis","authors":"Chuyu Wang ,&nbsp;Ying Zhao ,&nbsp;Yingfei Peng ,&nbsp;Wei Chen ,&nbsp;Jie Zhu ,&nbsp;Chenzheng Gu ,&nbsp;Ran Huo ,&nbsp;Lin Ding ,&nbsp;Yu Liu ,&nbsp;Te Liu ,&nbsp;Chunyan Zhang ,&nbsp;Wenjing Yang ,&nbsp;Hao Wang ,&nbsp;Wei Guo ,&nbsp;Beili Wang","doi":"10.1016/j.phymed.2025.156417","DOIUrl":"10.1016/j.phymed.2025.156417","url":null,"abstract":"<div><h3>Background</h3><div>Drug therapy plays an essential role in the management of hepatocellular carcinoma (HCC). Recently, the use of natural products to suppress tumor cells has emerged as a promising direction for drug development. Juglone, a natural compound, exhibits anticancer activities across various cancer types. However, the precise mechanism underlying the anticancer effect of juglone, especially in HCC, remains elusive.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the potential inhibitory effects of juglone on HCC and pan-cancer, as well as elucidate the underlying mechanism.</div></div><div><h3>Methods</h3><div>Cell Counting Kit-8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration. Cell cycle distribution was assessed by flow cytometry. The <em>in vivo</em> effect of juglone on HCC was evaluated by establishing the HCC xenograft mice model. RNA sequencing and inhibitors targeting diverse modes of programmed cell death were applied to uncover the form of juglone-induced cell death. Integrated transcriptomic, and proteomic analyses unveiled the underlying mechanism. The dual-luciferase reporter assay was employed to verify the findings. The pan-cancer value of juglone was assessed using TCGA database analysis and cellular assays.</div></div><div><h3>Results</h3><div>Juglone suppressed HCC growth via ferroptosis <em>in vitro</em> and <em>in vivo</em>, which is evidenced by increased levels of iron, lipid peroxidation (LPO), reactive oxygen species (ROS), malondialdehyde (MDA), and decreased levels of glutathione (GSH). Omic analyses, gene silencing and functional analyses showed the upregulated HMOX1 and FOSL1 were the key effector molecule and transcriptional factor in juglone-induced ferroptosis, respectively. The binding site of FOSL1 at the promoter of HMOX1 was identified. Juglone could induce ferroptosis in pan-cancer by activating the FOSL1-HMOX1 axis.</div></div><div><h3>Conclusion</h3><div>Our findings, for the first time, demonstrate that juglone effectively inhibits tumor growth by inducing FOSL1-HMOX1-dependent ferroptosis, thereby offering a promising strategy for the development of anticancer drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156417"},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350494","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}
引用次数: 0
Exploring the active components and potential mechanisms of Zhimu-Huangbai herb-pair in the treatment of depression
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-24 DOI: 10.1016/j.phymed.2025.156365
Xia Lei , Deping Zhao , Tongtong Chen , Qing Li , Ao Xue , Zhuoyi Hu , Fan jia , Xiaoliang Li
{"title":"Exploring the active components and potential mechanisms of Zhimu-Huangbai herb-pair in the treatment of depression","authors":"Xia Lei ,&nbsp;Deping Zhao ,&nbsp;Tongtong Chen ,&nbsp;Qing Li ,&nbsp;Ao Xue ,&nbsp;Zhuoyi Hu ,&nbsp;Fan jia ,&nbsp;Xiaoliang Li","doi":"10.1016/j.phymed.2025.156365","DOIUrl":"10.1016/j.phymed.2025.156365","url":null,"abstract":"<div><h3>Background</h3><div>The Zhimu-Huangbai herb-pair (ZB) is commonly used to treat depression. Previous research has verified that ZB is effective as an antidepressant. Nevertheless, its active components and potential mechanism still require further elucidation.</div></div><div><h3>Purpose</h3><div>This study aims to analyze the compounds of ZB penetrating into the brain using UPLC-MS and investigate the potential mechanisms of ZB in the treatment of depression through <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Methods</h3><div>The compounds of ZB that penetrate into the brain were identified using the UPLC-MS method. Network pharmacology analysis was employed to predict the therapeutic targets and mechanisms of the compounds of ZB in the brain for the treatment of depression. Subsequently, the molecular docking method was used to analyze the binding between active compounds and target proteins. Rat depression models induced by CUMS were used to investigate the impact of ZB on depression. Finally, the mechanism of ZB treatment for depression was investigated using the LPS-induced BV2 cell inflammation model.</div></div><div><h3>Results</h3><div>A total of 17 compounds were identified in ZB that crossed the blood-brain barrier (BBB). The network pharmacological analysis showed that the anti-depressant mechanism of ZB is closely related to inflammatory cytokines, including TNF and IL-6. Furthermore, KEGG and PPI analyses demonstrated that ZB regulates the microglia M1/M2 phenotypic polarization by modulating inflammation-related pathways. ZB was found to improve depression-like behavior <em>in vivo</em>. The molecular docking indicated that the compounds in ZB that penetrate into the brain have a strong binding ability to RELA and PPAR-γ. ZB inhibited the expression of p-p65 and increased the expression of PPAR-γ in the mPFC. By rebalancing the ratio of pro-inflammatory/anti-inflammatory cytokines, ZB was able to reduce neuroinflammation in the mPFC and hippocampus regions. The immunofluorescence results showed that ZB-containing serum reduced M1 polarization induced by LPS in BV2 cells.</div></div><div><h3>Conclusion</h3><div>This study reveals that ZB effectively alleviates depression by regulating the M1/M2 phenotypic polarization of microglial cells. The mechanism may be that the active compounds of ZB reduce M1 phenotypic polarization by inhibiting P65 and increase M2 phenotypic polarization by promoting PPARγ.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156365"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101384","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}
引用次数: 0
Ginsenoside Rh2(S) maintains cytoskeleton homeostasis and inhibits pyroptosis to resist cisplatin-induced cardiotoxicity through FGFR1/HRAS axis
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-24 DOI: 10.1016/j.phymed.2025.156425
Hongbo Teng , Shuai Huang , Xialin Sun , Haohao Wang , Xv Wang , Wenxin Zhang , Haijing Wang , Shurong Qu , Zhengxuan Yu , Yan Zhao , Shuangli Liu
{"title":"Ginsenoside Rh2(S) maintains cytoskeleton homeostasis and inhibits pyroptosis to resist cisplatin-induced cardiotoxicity through FGFR1/HRAS axis","authors":"Hongbo Teng ,&nbsp;Shuai Huang ,&nbsp;Xialin Sun ,&nbsp;Haohao Wang ,&nbsp;Xv Wang ,&nbsp;Wenxin Zhang ,&nbsp;Haijing Wang ,&nbsp;Shurong Qu ,&nbsp;Zhengxuan Yu ,&nbsp;Yan Zhao ,&nbsp;Shuangli Liu","doi":"10.1016/j.phymed.2025.156425","DOIUrl":"10.1016/j.phymed.2025.156425","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer undergoing cisplatin chemotherapy frequently experience cardiotoxic side effects that significantly affect their prognosis and survival rates. Our study found that Panax ginseng root extract exerted a significant protective effect against cisplatin-induced myocardial cell injury.</div></div><div><h3>Purpose</h3><div>The present study aims to elucidate the underlying mechanisms by which the bioactive components of Panax ginseng mitigate cisplatin-induced cardiotoxicity (CIC).</div></div><div><h3>Methods</h3><div>In vitro, the candidate active components were screened by network pharmacological prediction and in neonatal rat ventricular myocytes (NRVMs), and their mechanisms of action were verified by transcriptome sequencing, western blotting, gene overexpression, immunoprecipitation, immunofluorescence, and cellular thermal shift assays. A C57BL/6 CIC mouse model was established to verify the protective effects of the candidate components and the in vivo mechanism of the candidate components.</div></div><div><h3>Results</h3><div>Through network pharmacology prediction and cellular activity screening of ginseng root compounds, ginsenoside Rh2(S) (Rh2) was identified as a significant active component. Transcriptomic, in vitro, and in vivo experiments demonstrated that Rh2 can activate the Pak1/Limk1/cofilin phosphorylation pathway, thereby inactivating the actin-severing protein cofilin and protecting cardiomyocytes from cisplatin-induced actin depolymerization. Additionally, Rh2 suppressed the ROS/caspase-3/GSDME pathway to inhibit cisplatin-induced pyroptosis. Furthermore, co-immunoprecipitation and overexpression experiments confirmed that Rh2 activated the FGFR1/HRAS axis, thereby simultaneously regulating the two aforementioned pathways to combat CIC.</div></div><div><h3>Conclusions</h3><div>This study demonstrated for the first time that Rh2 is the main active component in Panax ginseng that maintains cytoskeletal homeostasis and inhibits pyroptosis by regulating the FGFR1/HRAS pathway to resist CIC. This study aimed to provide a theoretical basis for expanding the targets and pathways of CIC treatment, and for the development of related drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156425"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067251","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}
引用次数: 0
Targeting the NF-κB p65-MMP28 axis: Wogonoside as a novel therapeutic agent for attenuating podocyte injury in diabetic nephropathy
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-24 DOI: 10.1016/j.phymed.2025.156406
Xiandeng Li , Shuyan Zhao , Jing Xie , Mi Li , Shuangmei Tong , Jing Ma , Rui Yang , Qinjian Zhao , Jian Zhang , Ajing Xu
{"title":"Targeting the NF-κB p65-MMP28 axis: Wogonoside as a novel therapeutic agent for attenuating podocyte injury in diabetic nephropathy","authors":"Xiandeng Li ,&nbsp;Shuyan Zhao ,&nbsp;Jing Xie ,&nbsp;Mi Li ,&nbsp;Shuangmei Tong ,&nbsp;Jing Ma ,&nbsp;Rui Yang ,&nbsp;Qinjian Zhao ,&nbsp;Jian Zhang ,&nbsp;Ajing Xu","doi":"10.1016/j.phymed.2025.156406","DOIUrl":"10.1016/j.phymed.2025.156406","url":null,"abstract":"<div><h3>Background</h3><div>Although recent progress provides mechanistic insights into diabetic nephropathy (DN), effective treatments remain scarce. DN, characterized by proteinuria and a progressive decline in renal function, primarily arises from podocyte injury, which impairs the glomerular filtration barrier. Wogonoside, a bioactive compound from the traditional Chinese herb <em>Scutellaria baicalensis</em>, has not been explored for its role in DN.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the therapeutic effects of wogonoside on podocyte injury in DN and its molecular mechanisms.</div></div><div><h3>Methods</h3><div>The effects of wogonoside were examined using HFD/STZ-induced DN mouse models and high glucose (HG)-induced MPC-5 cells. Oxidative stress and inflammation markers were analyzed via Western blot and RT-qPCR. Wogonoside targets were identified through DARTS-MS and validated by SPR, molecular docking, alanine scanning, and CETSA. RNA-Seq analysis was employed to identify downstream targets, and the p65-MMP28 axis was explored through <em>p65</em> knockdown and overexpression studies. The regulatory effect of p65 on Mmp28 was confirmed through dual-luciferase reporter assays and ChIP-qPCR.</div></div><div><h3>Results</h3><div>Wogonoside treatment significantly reduced oxidative stress and inflammation in vivo and in vitro. Mechanistic studies identified p65 as a direct target of wogonoside, with SPR confirming a strong binding affinity (<em>K<sub>D</sub></em> = 25.05 μM). Molecular docking and alanine scanning identified LYS221 as a critical binding site, which was further supported by CETSA using the p65 K221A mutant. RNA-Seq analysis revealed <em>Mmp28</em> as a downstream effector of p65 involved in HG-induced podocyte injury. Functional studies demonstrated that wogonoside's protective effects on antioxidant and inflammatory pathways are mediated via the p65-MMP28 axis. Dual-luciferase reporter assays revealed that p65 regulates <em>Mmp28</em> transcription, and ChIP-qPCR confirmed its direct promoter binding.</div></div><div><h3>Conclusions</h3><div>This study highlights wogonoside as a promising candidate for the treatment of podocyte injury in DN by targeting the NF-κB p65-MMP28 signaling axis. These findings provide novel insights into wogonoside's therapeutic potential and its molecular mechanisms, paving the way for its further development as a DN intervention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156406"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041194","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}
引用次数: 0
Xin-Ji-Er-Kang balances mitochondrial fusion and fission to protect cardiomyocytes in mice with heart failure by regulating the ERα/SIRT3 pathway
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-23 DOI: 10.1016/j.phymed.2025.156420
Wei-wei Cai , Yuan-yuan Qin , Fei Ge , Qing Zhou , Lei Huang , Pang-bo Yang , Jie Xia , Ke-ke Li , Yi-fan Hou , Jia-min Wu , Ding-Yan Wang , Ya You , Wen-jie Lu , Shan Gao
{"title":"Xin-Ji-Er-Kang balances mitochondrial fusion and fission to protect cardiomyocytes in mice with heart failure by regulating the ERα/SIRT3 pathway","authors":"Wei-wei Cai ,&nbsp;Yuan-yuan Qin ,&nbsp;Fei Ge ,&nbsp;Qing Zhou ,&nbsp;Lei Huang ,&nbsp;Pang-bo Yang ,&nbsp;Jie Xia ,&nbsp;Ke-ke Li ,&nbsp;Yi-fan Hou ,&nbsp;Jia-min Wu ,&nbsp;Ding-Yan Wang ,&nbsp;Ya You ,&nbsp;Wen-jie Lu ,&nbsp;Shan Gao","doi":"10.1016/j.phymed.2025.156420","DOIUrl":"10.1016/j.phymed.2025.156420","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dynamics imbalance is an essential pathological mechanism in heart failure (HF). The Chinese herbal formula Xin-Ji-Er-Kang (XJEK) has demonstrated good therapeutic effects in various cardiovascular disease models. However, whether XJEK treats HF by regulating mitochondrial dynamics homeostasis and its specific molecular mechanisms remain elusive.</div></div><div><h3>Purpose</h3><div>To investigate the effect of XJEK on restoring the disrupted mitochondrial dynamics homeostasis in HF and elucidate the potential regulatory mechanism.</div></div><div><h3>Study-design/methods</h3><div>A mouse model of myocardial ischemia-reperfusion (MIR)-induced HF was established to assess the cardioprotection of XJEK. Subsequently, network pharmacology was employed to predict the mechanism by which XJEK treated HF. Moreover, gene silencing was employed to explore the potential mechanisms behind the cardioprotective effects of XJEK in AC16 cells subjected to hypoxia/reoxygenation (H/R).</div></div><div><h3>Results</h3><div>XJEK treatment significantly attenuated myocardial fibrosis and ameliorated ventricular remodeling in post-MIR-induced HF mice. Network pharmacology analysis identified the estrogen receptor α (ERα) as a key regulator of XJEK-mediated cardioprotection. XJEK disordered mitochondrial dynamics in the hearts of MIR-induced HF mice. In addition, XJEK restored mitochondrial fusion-fission imbalance and facilitated ERα nuclear translocation to up-regulate sirtuin 3 (SIRT3) expression in the hearts of MIR-induced HF mice and H/R-induced AC16 cells. Notably, ERα depletion in cardiomyocytes completely abrogated the cardioprotective effects of XJEK.</div></div><div><h3>Conclusion</h3><div>XJEK safeguards the hearts in mice with MIR-induced HF by facilitating ERα nuclear translocation to up-regulate SIRT3 expression to rescue the mitochondrial fusion-fission imbalance. This study establishes a new theoretical basis for treating HF with XJEK.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156420"},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304848","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}
引用次数: 0
Recent advances in delivery systems of ginsenosides for oral diseases
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-23 DOI: 10.1016/j.phymed.2025.156422
Yuqing Gu , Ze Li , Shu Zhou , Guanghong Han
{"title":"Recent advances in delivery systems of ginsenosides for oral diseases","authors":"Yuqing Gu ,&nbsp;Ze Li ,&nbsp;Shu Zhou ,&nbsp;Guanghong Han","doi":"10.1016/j.phymed.2025.156422","DOIUrl":"10.1016/j.phymed.2025.156422","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenosides, the principal active ingredients in ginseng, have anti-bacterial, anti-inflammatory, antioxidant, anticancer, osteogenic, cardioprotective, and neuroprotective properties. Oral diseases afflict about half of the world's population. Ginsenosides' multifunctional properties have led to substantial investigation into their potential to prevent and treat oral disorders. However, their low absorption and poor targeting limit their effectiveness.</div></div><div><h3>Purpose</h3><div>This review summarizes the latest research progress on ginsenoside-based drug delivery systems and the potential of ginsenosides in preventing and treating oral diseases to provide a theoretical basis for clinical applications.</div></div><div><h3>Methods</h3><div>Using \"ginsenoside\", \"drug delivery\", \"nanoparticles\", \"liposomes\", \"hydrogel\", \"oral disease\", \"toxicology\", \"pharmacology\", \"clinical translation\" and combinations of these keywords in PubMed, Web of Science, and Science Direct. The search was conducted until December 2024.</div></div><div><h3>Results</h3><div>The limitations of natural ginsenosides can be overcome by utilizing drug delivery systems to improve pharmacological activity, bioavailability and targeting. The multifunctional pharmacological activities of ginsenosides offer promising avenues for treating oral diseases. In addition, the susceptibility of the oral cavity to infection by pathogenic bacteria and the diluting effect of saliva pose significant challenges to treatment. The emergence of drug delivery marks a breakthrough in addressing these issues.</div></div><div><h3>Conclusion</h3><div>Ginsenoside-based drug delivery methods improve bioactivity, targeting, and reduce costs. This review emphasizes current advancements in ginsenosides within novel drug delivery systems, specifically on its potential in preventing and treating oral disorders. However, multiple well-designed clinical trials are needed to further evaluate the efficacy and safety of these drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156422"},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403245","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}
引用次数: 0
Traditional Chinese medicine Chaiqinchengqi decoction for patients with acute pancreatitis: A randomized clinical trial
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-23 DOI: 10.1016/j.phymed.2025.156393
Lihui Deng , Zhiyao Chen , Tao Jin , Fei Cai , Yanqiu He , Yuxin Shen , Shihang Zhang , Jia Guo , Xiaonan Yang , Lin Yang , Huimin Lu , Chunhui Wang , Wenfu Tang , Ziqi Lin , Lan Li , Qingyuan Tan , Ping Zhu , Xiaoxin Zhang , Na Shi , Cheng Hu , Qing Xia
{"title":"Traditional Chinese medicine Chaiqinchengqi decoction for patients with acute pancreatitis: A randomized clinical trial","authors":"Lihui Deng ,&nbsp;Zhiyao Chen ,&nbsp;Tao Jin ,&nbsp;Fei Cai ,&nbsp;Yanqiu He ,&nbsp;Yuxin Shen ,&nbsp;Shihang Zhang ,&nbsp;Jia Guo ,&nbsp;Xiaonan Yang ,&nbsp;Lin Yang ,&nbsp;Huimin Lu ,&nbsp;Chunhui Wang ,&nbsp;Wenfu Tang ,&nbsp;Ziqi Lin ,&nbsp;Lan Li ,&nbsp;Qingyuan Tan ,&nbsp;Ping Zhu ,&nbsp;Xiaoxin Zhang ,&nbsp;Na Shi ,&nbsp;Cheng Hu ,&nbsp;Qing Xia","doi":"10.1016/j.phymed.2025.156393","DOIUrl":"10.1016/j.phymed.2025.156393","url":null,"abstract":"<div><h3>Background</h3><div>Chaiqinchengqi decoction, a traditional Chinese medicine, has shown promising effects in in vitro, animal and preliminary small human studies for acute pancreatitis, but evidence of clinical practice is limited.</div></div><div><h3>Purpose</h3><div>To investigate whether Chaiqinchengqi decoction could improve clinical outcomes in patients with acute pancreatitis.</div></div><div><h3>Study Design</h3><div>Prospective, pragmatic, randomized controlled trial. (Chictr.org.cn registration number: ChiCTR2000034325)</div></div><div><h3>Methods</h3><div>This trial was conducted at West China Hospital of Sichuan University, China. Patients with acute pancreatitis were randomly assigned to receive either Chaiqinchengqi decoction or placebo by oral and rectal enemas in addition to guideline-directed administrations using a 1:1 ratio. The intervention of Chaiqinchengqi and placebo was determined by the grading of acute gastrointestinal injury. Patients were assessed within 24 and 48 hours, and on 3, 5, and 7 days after admission, or organ failure normalized. Survivors were followed up at 1, 3, and 6 months after discharge. Primary outcome was the duration of respiratory failure to 28 days after enrollment. Secondary outcomes included other organ failure, local complications, 6-month all-cause mortality, inflammatory indicators, and related interventions.</div></div><div><h3>Results</h3><div>Among 248 patients enrolled, Chaiqinchengqi decoction shortened the duration of respiratory failure compared with the placebo (median [IQR], 1.0 [0.0 to 5.0] vs 3.0 [1.0-8.0] days; median difference, -1.0; 95% CI, -2.0 to 0.0, P=.001). There were significant differences in the duration of circulatory failure, the incidence of new-onset respiratory and cardiovascular and failure, the incidence of new organ failure, severity, intensive care unit need, pain visual analogue scale, pancreatitis activity scoring system, and EQ-5D-5L.</div></div><div><h3>Conclusion</h3><div>Chaiqinchengqi decoction as an adjunctive therapy significantly reduced the duration of respiratory failure and improved 6-month clinical outcomes of acute pancreatitis in addition to guideline-directed treatments. Further study is needed to elucidate the mechanism of action.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156393"},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067388","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}
引用次数: 0
Shuxuening injection improves myocardial injury after myocardial infarction by regulating macrophage polarization via the TLR4/NF-κB and PI3K/Akt signaling pathways
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-22 DOI: 10.1016/j.phymed.2025.156418
Xiaoshuai Zhang , Liuqing Yang , Kairui Feng , Hui Zhang , Yulong Chen , Weixia Li , Xiaoyan Wang , Mingliang Zhang , Yali Wu , Shiting Wei , Yajuan Zheng , Gaoquan Meng , Weiting Meng , Xiaofei Chen , Jinfa Tang
{"title":"Shuxuening injection improves myocardial injury after myocardial infarction by regulating macrophage polarization via the TLR4/NF-κB and PI3K/Akt signaling pathways","authors":"Xiaoshuai Zhang ,&nbsp;Liuqing Yang ,&nbsp;Kairui Feng ,&nbsp;Hui Zhang ,&nbsp;Yulong Chen ,&nbsp;Weixia Li ,&nbsp;Xiaoyan Wang ,&nbsp;Mingliang Zhang ,&nbsp;Yali Wu ,&nbsp;Shiting Wei ,&nbsp;Yajuan Zheng ,&nbsp;Gaoquan Meng ,&nbsp;Weiting Meng ,&nbsp;Xiaofei Chen ,&nbsp;Jinfa Tang","doi":"10.1016/j.phymed.2025.156418","DOIUrl":"10.1016/j.phymed.2025.156418","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Macrophage activation and polarization play pivotal roles in the inflammatory response and myocardial injury associated with myocardial infarction (MI). Modulating macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is a promising therapeutic approach for MI. Shuxuening injection (SXNI) is extensively utilized in clinical settings for MI treatment and has demonstrated therapeutic efficacy. However, the effects of SXNI on macrophage polarization post-MI and its underlying mechanisms remain insufficiently understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study is aimed to evaluate the effects of SXNI on macrophage polarization following MI and to elucidate its potential mechanisms of action.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A rat model of MI was established by ligation of the left anterior descending coronary artery. The cardioprotective effects of SXNI were assessed through echocardiography, TTC staining, Masson's trichrome staining, HE staining, TUNEL staining, and western blotting (WB). Macrophage polarization was evaluated using ELISA, immunofluorescence staining, and WB. An in vitro model of oxygen-glucose deprivation (OGD) was utilized to simulate MI in macrophages, and qRT-PCR was employed to examine M1/M2 polarization markers. UPLC-Q-TOF/MS was used to identify active components in SXNI. Network pharmacology analysis and molecular docking were utilized to predict the key targets and pathways, which were subsequently validated through WB and immunohistochemistry.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;SXNI improved cardiac function, reduced infarct size, and attenuated myocardial tissue damage and apoptosis in MI rats. Staining analyses indicated a reduction in M1 macrophages (CD86&lt;sup&gt;+&lt;/sup&gt;/CD68&lt;sup&gt;+&lt;/sup&gt;) and an increase in M2 macrophages (CD206&lt;sup&gt;+&lt;/sup&gt;/CD68&lt;sup&gt;+&lt;/sup&gt;) in SXNI-treated animals. &lt;em&gt;In vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; experiments demonstrated that SXNI decreased M1 markers and pro-inflammatory cytokines levels while increasing M2 markers and the production of anti-inflammatory and pro-angiogenic cytokines. UPLC-Q-TOF/MS analysis identified 18 active components in SXNI. Network pharmacology analysis and molecular docking implicated the TLR4/NF-κB and PI3K/Akt pathways as central mechanisms, which were further confirmed by WB and immunohistochemistry. SXNI inhibited the expression of TLR4 and phosphorylated NF-κB while enhancing phosphorylated PI3 K and Akt levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;SXNI modulates the TLR4/NF-κB and PI3K/Akt signaling pathways to promote the polarization of macrophages from the M1 to the M2 phenotype, thereby alleviating myocardial inflammation and injury. These findings provide a scientific basis for the clinical application of SXNI in MI management, and establish a scientific foundation for exploring novel therapeutic strategies for cardiovascular diseases based on macrophage polarizat","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156418"},"PeriodicalIF":6.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067379","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}
引用次数: 0
Formosanin C induces autophagy-mediated cell death in hepatocellular carcinoma through activating DUSP1/AMPK/ULK1/Beclin1 signaling pathway
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-22 DOI: 10.1016/j.phymed.2025.156404
Zhikai Wen , Jinxia Qi , Qingqing Ruan , Chunmei Wen , Gang Huang , Zhan Yang , Jiale Xu , Zongjing Chen , Jie Deng
{"title":"Formosanin C induces autophagy-mediated cell death in hepatocellular carcinoma through activating DUSP1/AMPK/ULK1/Beclin1 signaling pathway","authors":"Zhikai Wen ,&nbsp;Jinxia Qi ,&nbsp;Qingqing Ruan ,&nbsp;Chunmei Wen ,&nbsp;Gang Huang ,&nbsp;Zhan Yang ,&nbsp;Jiale Xu ,&nbsp;Zongjing Chen ,&nbsp;Jie Deng","doi":"10.1016/j.phymed.2025.156404","DOIUrl":"10.1016/j.phymed.2025.156404","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is associated with poor survival. Formosanin C (FC) is a diosgenin glycoside extracted from Paris polyphylla. Therapeutic effects of FC against HCC malignancies remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to understand the anti-HCC effects of FC and to disclose the underlying mechanisms.</div></div><div><h3>Study design</h3><div>We evaluated the effects of FC on HCC malignancies by using two HCC cell lines, HepG2 and Huh-7, and a xenograft model.</div></div><div><h3>Methods</h3><div>Multiple assessment methods were used, including CCK-8, colony formation, flow cytometry, wound healing, transwell and Western blot. Bioinformatic analyses such as network pharmacology were also employed. Xenograft mouse model was used to evaluate <em>in vivo</em> efficacy.</div></div><div><h3>Results</h3><div>FC treatment remarkedly suppressed HepG2 and Huh-7 cell proliferation, migration and invasion, and induced cell apoptosis. Such anti-HCC effects of FC mainly attributed to the upregulation of DUSP1 expression and the subsequent activation of autophagy via AMPK/ULK1/Beclin1 axis. Inhibition of autophagy weakened the therapeutic effects of FC. Xenograft model analysis provided <em>in vivo</em> evidence that FC suppressed HCC tumor growth via DUSP1.</div></div><div><h3>Conclusions</h3><div>FC is therapeutically effective to suppress HCC malignancies principally via activation of the DUSP1/AMPK/ULK1/Beclin1-mediated autophagy. Our findings provide a novel promising drug candidate for treating HCC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156404"},"PeriodicalIF":6.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041204","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}
引用次数: 0
Duhuo Jisheng Mixture attenuates neuropathic pain by inhibiting S1PR1/P2Y1R pathway after Chronic Constriction Injury in mice
IF 6.7 1区 医学
Phytomedicine Pub Date : 2025-01-20 DOI: 10.1016/j.phymed.2025.156413
Ruili Li , Wei Zhang , Xiaodan Bai , Fan Wang , Minna Yao , Chao Zhao , Jingwen Wang
{"title":"Duhuo Jisheng Mixture attenuates neuropathic pain by inhibiting S1PR1/P2Y1R pathway after Chronic Constriction Injury in mice","authors":"Ruili Li ,&nbsp;Wei Zhang ,&nbsp;Xiaodan Bai ,&nbsp;Fan Wang ,&nbsp;Minna Yao ,&nbsp;Chao Zhao ,&nbsp;Jingwen Wang","doi":"10.1016/j.phymed.2025.156413","DOIUrl":"10.1016/j.phymed.2025.156413","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design and methods&lt;/h3&gt;&lt;div&gt;Chronic Constriction Injury (CCI) surgery was used to assess the efficiency of DJM in treating neuropathic pain. Forty-two C57BL/6 mice were evenly divided into seven groups: sham-operated, sham treatment with DJM (20 ml/kg), CCI treatment with DJM (0, 10, 20, or 40 ml/kg) and CCI treatment with Morphine (3 mg/kg). DJM irrigation stomach was implemented from post-operative day (POD) 0 to POD 21. Paw withdrawal threshold and Thermal latency were conducted on POD 0, 1, 3, 5, 7, 14 and 21. On POD 14, eEPSP in spinal dorsal horn neurons was recorded by patch-clamp. mRNA transcription in spinal cord was also monitored to screen molecular targets and signaling pathways on POD 14. To further validate the influence of DJM on the S1PR1 signaling pathway, 1 mg/kg W146 was infused into mice intrathecally and delivered to the cerebral spinal fluid through one 30 G needle with a whole 20 μl intervertebral between the L5 and L6. Furthermore, the active ingredients of DJM were identified through LC/MS equipment and predicted through Molecular Docking.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We demonstrated that DJM treatment reversed CCI-induced pain sensitivity and the excitability of neurons, decreased up-regulation of astrocyte S1PR1, inhibited astrocyte activation, and further inhibited the expression of Purinergic P2Y&lt;sub&gt;1&lt;/sub&gt;R and its downstream molecule p-JNK in mouse spinal cord, as well as the release of inflammatory factors. Interestingly, due to the regulatory role of astrocytes on neurons, the effects of DJM on astrocytes ultimately manifest in pain-effector neurons, resulting in decreased p-ERK, p-CREB, and pain-marking protein c-fos in neurons. S1PR1 Antagonist W146 possessed an equivalent analgesic effect as DJM and inhibited S1PR1 and c-fos expression. According to LC/MS analysis results, a total of 33 active ingredients were screened, of which 20 active ingredients had good binding activity with S1PR1 and were considered to be the main active ingredients for analgesia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study is the first to clarify the effect and molecular mechanism of DJM for anti-neuralgia in particular, which confirms the clinical value of DJM in relieving neuropathic pain. Furthermore, this study innovatively identifies the potential pharmacological components of DJM through LC/MS and Bioinformatics technology, which forms a framework for people's understanding of DJM treatment for neuropathic pain an","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156413"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041151","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}
引用次数: 0
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