Phytomedicine最新文献

{"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_D</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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Mitochondria-dependent apoptosis was involved in the alleviation of Jujuboside A on diabetic kidney disease-associated renal tubular injury via YY1/PGC-1α signaling","authors":"Tingting Yang ,&nbsp;Yuting Peng ,&nbsp;Yuting Shao ,&nbsp;Dandan Pan ,&nbsp;Qian Cheng ,&nbsp;Zhenzhou Jiang ,&nbsp;Sitong Qian ,&nbsp;Baojing Li ,&nbsp;Meng Yan ,&nbsp;Xia Zhu ,&nbsp;Junjie Liu ,&nbsp;Tao Wang ,&nbsp;Qian Lu ,&nbsp;Xiaoxing Yin","doi":"10.1016/j.phymed.2025.156411","DOIUrl":"10.1016/j.phymed.2025.156411","url":null,"abstract":"<div><h3>Background</h3><div>Renal tubular injury was a significant pathological change of diabetic kidney disease (DKD), and the amelioration of renal tubular injury through mitochondrial function was an important treatment strategy of DKD. Our previous study had revealed that Jujuboside A (Ju A), the main active substance isolated from <em>Semen Ziziphi Spinosae</em> (SZS), could restore renal function of diabetic mice. However, its protective mechanism against DKD remains unclear.</div></div><div><h3>Purpose</h3><div>To investigate the effects and the mechanism of Ju A against DKD-associated renal tubular injury.</div></div><div><h3>Study design and Methods</h3><div>The anti-apoptotic effect of Ju A and its protection effect on mitochondria dysfunction of renal tubular epithelial cells (RTECs) were examined in high glucose (HG)-cultured HK-2 cells, and in <em>db/db</em> mice. Subsequently, Network Pharmacology analysis, molecular docking, luciferase assay, chromatin immunoprecipitation (ChIP), Yin Yang 1 (YY1) overexpression lentiviral vector and peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α) specific agonist ZLN005 were all used to identify the protective mechanism of Ju A towards DKD-associated mitochondrial dysfunction of RTECs.</div></div><div><h3>Results</h3><div>Ju A inhibited RTECs apoptosis and ameliorated mitochondria dysfunction of RTECs of diabetic mice, and HG-cultured HK-2 cells. YY1 was the potential target of Ju A against DKD-related mitochondrial dysfunction, and the down-regulation of YY1 induced by Ju A increased PGC-1α promoter activity, leading to the restored mitochondrial function of HG-treated HK-2 cells. Renal tubule specific overexpression of YY1 intercepted the renal protective effect of Ju A on diabetic mice via blocking PGC-1α-mediated restoration of mitochondrial function of RTECs. The in-depth mechanism research revealed that the protective effect of Ju A towards DKD-associated renal tubular injury was linked to the restored mitochondrial function through YY1/PGC-1α signaling, resulting in the inhibited apoptosis of RTECs in diabetic condition via inactivating CytC-mediated Caspase9/Caspase3 signaling.</div></div><div><h3>Conclusion</h3><div>Ju A through the inhibition of mitochondria-dependent apoptosis alleviated DKD-associated renal tubular injury via YY1/PGC-1α signaling.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156411"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067350","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":"Modified Shenqi Dihuang Decoction inhibits prostate cancer metastasis by disrupting TCA cycle energy metabolism via NF-kB/p65-mediated OGDH regulation","authors":"Tongtong Zhang ,&nbsp;Jixiang Yuan ,&nbsp;Xiran Ju ,&nbsp;Jielong Zhou ,&nbsp;Xinyu Zhai ,&nbsp;Chuanmin Chu ,&nbsp;Mingyue Tan ,&nbsp;Guanqun Ju ,&nbsp;Jianyi Gu ,&nbsp;Dongliang Xu","doi":"10.1016/j.phymed.2025.156405","DOIUrl":"10.1016/j.phymed.2025.156405","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is a significant malignancy in men, particularly challenging in the metastatic stage due to poor prognosis and limited treatment efficacy. Traditional Chinese Medicine, particularly Modified Shenqi Dihuang Decoction (MSDD), has demonstrated promise in inhibiting PCa metastasis, although its mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>The efficacy of MSDD was evaluated using migration assays and a nude mouse model. Metabolomics was employed to identify the biological processes affected by MSDD. Systematic pharmacology, bioinformatics, and molecular dynamics were utilized to determine direct action targets of MSDD. Additionally, luciferase reporter assays, ChIP-qPCR, and gene editing were applied to elucidate the pharmacological mechanisms.</div></div><div><h3>Results</h3><div>MSDD effectively inhibited prostate metastasis both <em>in vivo</em> and <em>in vitro</em>, without significant adverse events reported. Metabolomics and molecular biology experiments indicated that MSDD transcriptionally represses OGDH, affecting energy metabolism associated with the tricarboxylic acid cycle (TCA) in PCa. The active components of MSDD were found to potentially bind to the transcription factor RELA (NF-kB-p65), and further experiments demonstrated that RELA regulates OGDH transcription. Further experiments revealed that the anti-metastatic effects of MSDD are RELA-dependent, indicating the crucial role of the NF-kB/OGDH axis in this process.</div></div><div><h3>Conclusions</h3><div>These findings support the clinical use of MSDD in metastatic PCa, emphasizing its potential to address current treatment gaps. The identified NF-kB/OGDH-dependent mechanism not only underpins MSDD's anti-metastatic effects but also reflects OGDH as a potential therapeutic target. Further research into the role of TCA in PCa progression is imperative.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156405"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029337","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":"Spatial metabolic modulation in vascular dementia by Erigeron breviscapus injection using ambient mass spectrometry imaging","authors":"Shuohan Cheng ,&nbsp;Wenbin Zhou ,&nbsp;Yuhe Ren ,&nbsp;Xuemeng Gao ,&nbsp;Dalun Cai ,&nbsp;Mengyu Li ,&nbsp;Zhi Zhou ,&nbsp;Zhonghua Wang ,&nbsp;Zeper Abliz","doi":"10.1016/j.phymed.2025.156412","DOIUrl":"10.1016/j.phymed.2025.156412","url":null,"abstract":"<div><h3>Background</h3><div>Vascular dementia (VaD), a significant cognitive disorder, is caused by reduced cerebral blood flow. Unraveling the metabolic heterogeneity and reprogramming in VaD is essential for understanding its molecular pathology and developing targeted therapies. However, the in situ metabolic regulation within the specific brain regions affected by VaD has not been thoroughly investigated, and the therapeutic mechanisms of <em>Erigeron breviscapus</em> injection (EBI), a traditional Chinese medicine, require further elucidation.</div></div><div><h3>Purpose</h3><div>To investigate the region-specific metabolic alterations in a VaD rat model, explore the therapeutic effects of EBI at a microregional level, identify the key metabolic pathways and metabolites involved in VaD, and elucidate how EBI modulates these pathways to exert its therapeutic effects.</div></div><div><h3>Methods</h3><div>Air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI), a novel technique, was employed to investigate the metabolic changes in the brain microregions. We used a bilateral common carotid artery occlusion model to induce VaD in rats. Network analysis and network pharmacology were used to assess the local metabolic effects of the EBI treatment (3.6 mL/kg/day for 2 weeks).</div></div><div><h3>Results</h3><div>The EBI treatment significantly ameliorated the neurological deficits in VaD rats. AFADESI–MSI revealed 31 key metabolites with significant alterations in the VaD model, particularly within the pathways related to neurotransmitter metabolism, redox homeostasis, and osmoregulation. The metabolic disturbances were primarily observed in the striatum (ST), pyriform cortex (PCT), hippocampus (HP), and other critical brain regions. The EBI treatment effectively reversed these metabolic imbalances, especially in neurotransmitter metabolism, suggesting its potential in mitigating VaD-related cognitive decline.</div></div><div><h3>Conclusion</h3><div>Our findings not only shed light on the molecular underpinnings of VaD but also highlight the potential of EBI as a therapeutic agent in neurodegenerative disorders. Moreover, this study demonstrates the power of advanced mass spectrometry imaging techniques in phytomedicine, offering new insights into the spatial metabolic changes induced by botanical treatments.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156412"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075185","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":"Gut microbiota as a new target for hyperuricemia: A perspective from natural plant products","authors":"Ling Dong ,&nbsp;Fengying Dong ,&nbsp;Pingping Guo ,&nbsp;Tianxing Li ,&nbsp;Yini Fang ,&nbsp;Yang Dong ,&nbsp;Xiaoxue Xu ,&nbsp;Tianqi Cai ,&nbsp;Shufei Liang ,&nbsp;Xinhua Song ,&nbsp;Lingru Li ,&nbsp;Wenlong Sun ,&nbsp;Yanfei Zheng","doi":"10.1016/j.phymed.2025.156402","DOIUrl":"10.1016/j.phymed.2025.156402","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia, a prevalent chronic metabolic disorder caused by purine metabolism disturbances, is characterized by elevated serum uric acid (UA) levels. Prolonged hyperuricemia can cause severe complications such as gout or kidney damage. However, the toxic side effects of and adverse reactions to UA-lowering drugs are becoming increasingly prominent. Therefore, new targets and drugs for hyperuricemia are needed.</div></div><div><h3>Purpose</h3><div>This review aims to summarize recent research progress on the prevention and treatment mechanisms for gut microbiota-hyperuricemia from the perspective of plant-derived natural products.</div></div><div><h3>Methods</h3><div>Data from PubMed, Web of Science, ScienceDirect, and the CNKI databases spanning from January 2020 to December 2024 were reviewed. The aim of this study is to categorize and summarize the relevant mechanisms through which natural products improve hyperuricemia via the gut microbiota. The retrieved data followed PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analyses).</div></div><div><h3>Results</h3><div>Regulating gut microbiota as a treatment for hyperuricemia. Targeting the gut microbiota could reduce host UA levels by promoting purine degradation, reducing UA production, and increasing UA excretion. Moreover, the gut microbiota also exerts anti-inflammatory and antioxidant effects that alleviate complications such as renal damage caused by hyperuricemia. Due to their diverse sources, multicomponent synergy, multitarget effects, and minimal side effects, plant-derived natural products have been extensively utilized in the management of hyperuricemia. Especially, utilizing natural products from plants to regulate the gut microbiota has become a new strategy for reducing UA levels.</div></div><div><h3>Conclusion</h3><div>This review comprehensively summarizes recent advances in understanding the preventive and therapeutic mechanisms of plant-derived natural products in ameliorating hyperuricemia and its comorbidities through gut microbiota modulation. This review contributes a novel perspective for the development of safer and more efficacious UA-lowering products.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156402"},"PeriodicalIF":6.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060367","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}