Phytomedicine最新文献

{"title":"Chlorogenic acid and ferulic acid in SMYAD alleviate diabetic cardiomyopathy by inhibiting cardiac lipotoxicity via GCGR/PPARα and GCGR/AMPK pathways","authors":"Lin Li ,&nbsp;Kai Huang ,&nbsp;Dong Wang ,&nbsp;Deshuang Yang ,&nbsp;Kuo Gao ,&nbsp;Jiayang Tang ,&nbsp;Xiaoqi Wei ,&nbsp;Haiyin Pu ,&nbsp;Jiang Yu ,&nbsp;Dongwei Zhang ,&nbsp;Shuzhen Guo","doi":"10.1016/j.phymed.2025.156906","DOIUrl":"10.1016/j.phymed.2025.156906","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic cardiomyopathy (DCM) causes a high risk of heart failure, necessitating effective therapies. The Si-Miao-Yong-An decoction (SMYAD) has been widely applied in the clinical management of diabetes mellitus and cardiovascular diseases within the paradigm of traditional Chinese medicine (TCM), but its active constituents and mechanism of the action against DCM are poorly understood.</div></div><div><h3>Purpose</h3><div>The aim of this study was to evaluate the effects of chlorogenic acid (CGA) and ferulic acid (FA), the main active ingredients of SMYAD, on cardiac function and cardiac lipotoxicity in mice with DCM, as well as to investigate their potential molecular mechanisms.</div></div><div><h3>Methods</h3><div>The cardioprotective effects of CGA and FA on DCM mice were identified by echocardiography, HE, Masson, and Oil Red O. Immunofluorescence, flow cytometry, MitoTracker Green staining, and seahorse analysis were used to study the effects of CGA and FA on palmitic acid (PA)-induced lipotoxicity in cardiomyocytes. Finally, the regulatory effects of CGA and FA on GCGR/PPARα and GCGR/AMPK signalling pathways were detected by Ad GCGR-infection, molecular docking, RT-PCR and western blot.</div></div><div><h3>Results</h3><div>Based on previously identified 20 representative blood prototype components and <em>in vitro</em> multilayer lipid toxicity analysis, chlorogenic acid (CGA) and ferulic acid (FA) were screened as the main active components of SMYAD against DCM. <em>In vivo</em> experiments showed that CGA and FA attenuated lipotoxicity associated with cardiac GLC/GCGR in DCM mice, thereby protecting cardiac function. <em>In vitro</em> results showed that GCGR inhibitor (Adomeglivant) reduces PA-induced apoptosis, indicating that PA leads to cardiomyocyte lipotoxic apoptosis by activating GCGR. Moreover, CGA and FA inhibit PA-induced cardiomyocyte lipotoxic apoptosis, mitochondrial dysfunction, and energy substrate transition through inhibiting GCGR/PPARα and GCGR/AMPK pathways. Furthermore, GLC-stimulated/GCGR-infected H9c2 cardiomyocyte lipotoxic apoptosis and downstream proteins were effectively suppressed by CGA and FA, which is consistent with the effect of Adomeglivant. Docking results showed that ASP1018 and THR1024 of GCGR are the principal molecular targets for both CGA and FA.</div></div><div><h3>Conclusion</h3><div>GLC lipotoxic signaling is a crucial target in mediating cardiac lipotoxicity development. CGA and FA could inhibit DCM by regulating the GCGR/PPARα and GCGR/AMPK pathway, offering a novel strategy for the development of anti-DCM drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156906"},"PeriodicalIF":6.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194841","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":"Poliumoside alleviates microglia-mediated inflammation and blood-brain barrier disruption via modulating the polarization of microglia after ischemic stroke in mice","authors":"Yuxiao Gao ,&nbsp;Jingjing Wang ,&nbsp;Cong Zhang ,&nbsp;Huan Wang ,&nbsp;Bin Wang ,&nbsp;Xiangjian Zhang","doi":"10.1016/j.phymed.2025.156881","DOIUrl":"10.1016/j.phymed.2025.156881","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke remains a life-threatening condition with limited therapeutic options. Microglia-mediated neuroinflammation critically exacerbates acute ischemic injury. The active compound poliumoside (Pol) in <em>Callicarpa kwangtungensis Chun</em> exhibits significant anti-inflammatory effects. The therapeutic potential of Pol for ischemic stroke remains unknown and promising.</div></div><div><h3>Purpose</h3><div>The current study aimed to investigate the effect of Pol on acute ischemic stroke in mice, and to elucidate the underlying mechanisms.</div></div><div><h3>Study design and methods</h3><div>Ischemic stroke mice model was induced by transient middle cerebral artery occlusion model (tMCAO). Pol was administered by intraperitoneal injection after stroke. Neurological deficits were monitored up to 3 days after stroke. Microglial polarization, and microglia-associated inflammatory cytokines and blood-brain barrier (BBB) integrity were detected in the peri‑infarct cortex at day 1 after stroke. RNA-seq analysis was performed to identify potential pathways recruited by Pol. Primary cortical neuron, BV2 microglia cell lines and mouse brain microvascular endothelial cell lines(bEnd.3) were employed to explore the underlying mechanism in <em>vitro</em>.</div></div><div><h3>Results</h3><div>Compared with the tMCAO group, Pol significantly alleviated neurological deficits and reduced infarct size in mice. In <em>vitro</em> and in <em>vivo</em> experiments demonstrated that Pol regulates microglial polarization, down-regulates inflammatory factor levels (IL-6 and TNF-α), and attenuates inflammation-mediated BBB damage while maintaining tight junction proteins expression (ZO-1, claudin-5, occludin). Through investigation of the underlying mechanism combined with RNA-seq analysis and experimental results, we established that Pol down-regulated the JAK/STAT3 pathway both in <em>vitro</em> and in <em>vivo,</em> which was corroborated by the use of the JAK inhibitor tofacitinib<em>.</em></div></div><div><h3>Conclusion</h3><div>Pol regulates microglial polarization in ischemic stroke by down-regulating JAK/STAT3 signaling pathway, alleviating the microglia-mediated inflammatory response and the destruction of blood-brain barrier.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156881"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177814","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":"Daidzein alleviates ethanol-induced acute gastric injury in rats by targeting ESR1 and activating the PI3K/AKT/CREB signaling pathway","authors":"Tao Jiang ,&nbsp;Shengyi Du ,&nbsp;Zexin Wang ,&nbsp;Qichao Hu ,&nbsp;Lingshun Zeng ,&nbsp;Yuan Chen ,&nbsp;Xiyue Tan ,&nbsp;Yi Zeng ,&nbsp;Lingping Fu ,&nbsp;Fangli Hu ,&nbsp;Kun Xiao ,&nbsp;Xiao Ma ,&nbsp;Jinhao Zeng ,&nbsp;Yanling Zhao","doi":"10.1016/j.phymed.2025.156887","DOIUrl":"10.1016/j.phymed.2025.156887","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol-induced gastric ulcers (GU) rank among the most prevalent upper gastrointestinal diseases, severely impacting patients’ quality of life and health. Daidzein (DAI), one of the primary active compounds present in soybeans and other edible plants, has been reported to exert potential therapeutic effects on GU.</div></div><div><h3>Purpose</h3><div>This study sought to explore the potential mechanisms through which DAI alleviates alcohol-induced acute GU in rats.</div></div><div><h3>Methods</h3><div>In this study, <em>in vitro</em> and <em>in vivo</em> models of alcohol-induced GU were established and employed a range of experimental techniques, including Immunofluorescence (IF), Cellular thermal shift assay (CETSA), Transmission Electron Microscopy (TEM), Immunohistochemistry (IHC), Western Blotting (WB), and Real-time quantitative PCR (RT- qPCR), to assess the protective effects of DAI. Next, network pharmacology, virtual screening, and molecular dynamics simulations were employed to identify the potential targets and mechanisms responsible for DAI’s therapeutic action on GU. Finally, the activation of the PI3K/AKT/CREB signaling pathway was validated in both a rat model and a GES-1 cell model.</div></div><div><h3>Results</h3><div>DAI was shown to alleviate inflammation, oxidative stress, and apoptosis, while mitigating the reduction of H⁺/K⁺-ATPase and EGFR, thereby restoring the gastric barrier. In both <em>in vitro</em> and <em>in vivo</em> models, DAI showed stable binding to key residues of ESR1 (Leu387A, Arg394A, His524A, and Glu353A), and subsequently activated the PI3K/AKT/CREB signaling pathway. Notably, Fulvestrant (a selective ESR1 inhibitor) and LY294002 (a PI3K inhibitor) both abrogated the activation of this pathway.</div></div><div><h3>Conclusion</h3><div>DAI inhibited apoptosis and preserved mucosal integrity by targeting ESR1 to activate the PI3K/AKT/CREB signaling pathway. The research elucidated the mechanisms and clinical value of DAI in the treatment of GU, offering a reference for its application as a gastric mucosal protectant in drug development and dietary supplements.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156887"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of a novel nonsteroidal organoselenium compound SLL-1-43 on ulcerative colitis through down-regulating NOX2 signaling pathway in vitro and in vivo","authors":"Lili Chen ,&nbsp;Wenqian Pang ,&nbsp;Xiaoqin Luo ,&nbsp;Tianyu Li ,&nbsp;Qingqing Ju ,&nbsp;Zhe Yang ,&nbsp;Xianran He ,&nbsp;Xiaolong Li ,&nbsp;Yuebin Ge ,&nbsp;Xiuli Bi","doi":"10.1016/j.phymed.2025.156899","DOIUrl":"10.1016/j.phymed.2025.156899","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a global health concern characterized by chronic inflammation and oxidative stress. These factors play pivotal roles in its pathogenesis, highlighting the need for novel therapeutic strategies. In this study, we synthesized and screened nine non-steroidal organicselenium compounds to evaluate their potential efficacy against UC, identifying SLL-1–43 and SLL-1–44 as the most promising candidates.</div></div><div><h3>Purpose</h3><div>To investigate the therapeutic potential of SLL-1–43 and SLL-1–44 in UC and elucidate the underlying molecular mechanisms.</div></div><div><h3>Study design</h3><div>We conducted in vitro experiments using LPS-induced RAW264.7 macrophages and in vivo studies on DSS-induced acute and chronic UC mouse models.</div></div><div><h3>Methods</h3><div>The expression levels of inflammatory and oxidative stress-related genes (iNOS, IL-1β, IL-18, and p47phox) were analyzed using quantitative PCR. Molecular docking and molecular dynamics simulations were performed to assess the interactions between SLL-1–43, SLL-1–44, and NOX2/p47phox. Western blot analysis was employed to examine protein expression, while clinical symptoms in DSS-induced UC mice were evaluated.</div></div><div><h3>Results</h3><div>Treatment with SLL-1–43 or SLL-1–44 significantly suppressed the mRNA expression of pro-inflammatory mediators in LPS-stimulated RAW264.7 macrophages. Molecular docking and dynamics simulations confirmed stable interactions between these compounds and NOX2/p47phox. Additionally, SLL-1–43 downregulated NOX2/p47phox expression and its downstream signaling pathways. In DSS-induced UC mice, SLL-1–43 improved clinical symptoms by modulating key molecular targets, including gp91phox, p47phox, NLRP3, Nrf2, and tight junction proteins, thereby alleviating inflammation and oxidative stress.</div></div><div><h3>Conclusion</h3><div>SLL-1–43 exhibits potent anti-inflammatory and protective effects against UC in vitro and in vivo by suppressing the NOX2 signaling pathway. These findings suggest that SLL-1–43 may serve as a promising candidate for UC therapy and new drug development.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156899"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185592","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":"Hedyotis chrysotricha aqueous extract inhibits hepatitis B surface antigen and viral replication via hepatocyte nuclear factor 4α regulation","authors":"Yina Yu ,&nbsp;Haoyang Hu ,&nbsp;Yichun Zhang ,&nbsp;Zhijuan Zhang ,&nbsp;Shuaibing Ying ,&nbsp;Shaohua Dong ,&nbsp;Jinyao Dai ,&nbsp;Yuqi Hong ,&nbsp;Yunqing Qiu ,&nbsp;Yan Lou","doi":"10.1016/j.phymed.2025.156726","DOIUrl":"10.1016/j.phymed.2025.156726","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic hepatitis B virus (HBV) infection continues to pose a significant global public health challenge, as current antiviral treatments have not yet succeeded in completely eradicating the virus. Traditional Chinese Medicine (TCM) offers unique advantages in treating chronic hepatitis B. Furthermore, the aqueous extract of &lt;em&gt;Hedyotis chrysotricha&lt;/em&gt; (Palib.) Merr (HCM), a synonym of &lt;em&gt;Exallage chrysotricha&lt;/em&gt; (Palib.) Neupane &amp; N.Wikstr., has shown potential anti-HBV properties. Nevertheless, its pharmacological effects and precise mechanisms of action remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;We aim to evaluate the anti-HBV efficacy of the aqueous extract of HCM and investigate its underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;Ultra performance liquid chromatography-triple time-of-flight mass spectrometry (UPLC-Triple-TOF/MS) was used to identify the HCM components, and the anti-HBV efficacy of HCM was evaluated using a transgenic HBV mouse model, as well as the HepG2.2.15 and HepAD38 HBV cell lines.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We first identified the chemical components of HCM using UPLC-Triple-TOF/MS, combined with relevant reference standards. Quantification was achieved using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), followed by methodology validation. We used a transgenic HBV mouse model along with the HepG2.2.15 and HepAD38 HBV cell lines to assess its anti-HBV efficacy. Besides, network pharmacology, molecular docking and transcriptomics were employed to explore the underlying anti-HBV mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;UPLC analysis, using authentic reference standards, identified 19 major chemical components in HCM, including isorhamnetin, monotropein, sesamoside, and kaempferol, which were newly identified as components in this matrix. Our study demonstrates that HCM significantly inhibited HBV replication and transcription in both the transgenic HBV mouse model and HBV cell lines, with a notable reduction in HBsAg levels and the potential inhibition of cccDNA, which serves as a stable viral DNA reservoir in the nucleus of infected hepatocytes, driving the replication and persistence of HBV. Further analysis using network pharmacology and transcriptomic approaches suggests that the anti-hepatitis B mechanism may involve the upregulation of the phosphatidylinositol 3-kinase - protein kinase B (PI3K-AKT) and mitogen-activated protein kinase - extracellular signal-regulated kinase 1 and 2 (MAPK-ERK1/2) pathways. Additionally, hepatocyte nuclear factor 4α (HNF4α) was shown to play a critical role in HBV inhibition, with its function negatively regulated by the PI3K-AKT and MAPK-ERK1/2 pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The aqueous extract of HCM not only inhibits HBV replication and transcription but also significantly suppresses HBsAg levels. The underlying mechanism likely involves the concurr","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156726"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124758","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":"Metabolomics and integrated network pharmacology analysis revealed multi-targeted anti-cancer effect of FuZhengXiaoJi decoction against non-small cell lung cancer","authors":"Xinyuan Jiang ,&nbsp;Zhiyong Xu ,&nbsp;Huan Wang ,&nbsp;Jiangnan Zhao ,&nbsp;Nueraili Maihemuti ,&nbsp;Sujing Jiang ,&nbsp;Mingshu Xiao ,&nbsp;Kaiyue Zhang ,&nbsp;Sibei Liang ,&nbsp;Yueli Shi ,&nbsp;Kai Wang","doi":"10.1016/j.phymed.2025.156855","DOIUrl":"10.1016/j.phymed.2025.156855","url":null,"abstract":"<div><h3>Background and purpose</h3><div>As a malignant tumor characterized by a dismal prognosis and a high mortality rate, non-small cell lung cancer (NSCLC) presents significant challenges in contemporary treatment. These challenges include drug resistance and side effects, which severely hamper the effectiveness of current therapeutic strategies. An increasing number of herbal formulas have been utilized in antitumor therapy, owing to their cost-effectiveness, beneficial efficacy, and additional advantages. FuZhengXiaoJi Decoction (FZXJD), a cancer-treating formula, has been successfully applied in NSCLC clinical treatment, but the underlying mechanism remains elusive. Therefore, this paper integrated multiple analytical methods, including network pharmacology, metabolomics, biological approaches, and molecular docking to clarify how FZXJD suppresses NSCLC.</div></div><div><h3>Methods</h3><div>This study assessed the anti-NSCLC efficacy of FZXJD using in vitro assays and lung cancer xenograft models, and the primary components and potential mechanisms of FZXJD inhibition of NSCLC were identified by high-performance liquid chromatography (HPLC) and network pharmacology. Subsequently, inhibitory mechanisms of FZXJD and its principal effector component oleanolic acid (OA) on NSCLC were explored by molecular docking, as well as biological experiments. Finally, effects of FZXJD on critical metabolic pathways in tumors were further investigated by metabolomics and metabolite enrichment analysis.</div></div><div><h3>Results</h3><div>Inhibition of FZXJD on NSCLC cells was confirmed in vitro experiments. Correspondingly, <em>in vivo</em> experiments revealed that FZXJD impeded tumor progression without obvious toxic side effects. Network pharmacology and molecular docking disclosed that target genes involved in FZXJD’s inhibition of NSCLC were significantly enriched in the PI3K/AKT and ERK/MAPK signaling pathways. Additionally, 14 core genes (HSP90AA1, VEGFA, AKT1, JUN, EGFR, CASP3, ESR1, ERBB2, STAT3, MTOR, SRC, MDM2, CCND1, MAPK3) as well as the main component of the antitumor effect of FZXJD, the OA, were also identified. Biological experiments and molecular docking demonstrated that FZXJD and OA exerted antitumor effects by inhibiting two significant pathways, PI3K/AKT and ERK/MAPK. Metabolomics analysis indicated that FZXJD treatment suppressed glutathione metabolism <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>FZXJD and its main active ingredient, OA, impede NSCLC progression by inhibiting PI3K/AKT and ERK/MAPK signaling pathways. FZXJD treatment also markedly attenuates glutathione metabolism. This research provides a promising strategy for the application of herbal formulas in NSCLC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156855"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177818","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":"Periplocin targets LRP4 to regulate metabolic homeostasis and anti-inflammation for the treatment of IVDD","authors":"Zhenchuan Liu ,&nbsp;Fei Qiao ,&nbsp;Dejian Liu ,&nbsp;Xiangzhen Kong ,&nbsp;Kaiwen Liu ,&nbsp;Hanwen Gu ,&nbsp;Yuanqiang Zhang ,&nbsp;Qunbo Meng ,&nbsp;Lei Cheng","doi":"10.1016/j.phymed.2025.156885","DOIUrl":"10.1016/j.phymed.2025.156885","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) is characterized by deteriorating intervertebral discs, leading primarily to low back pain and leg pain. Most current treatments for IVDD primarily address symptoms without targeting the underlying degenerative process. Moreover, tumor necrosis factor-α (TNF-α)-mediated inflammation and degradation of the nucleus pulposus (NP) extracellular matrix (ECM) influence this pathological process. Periplocin, a cardiotonic steroid extracted from <em>periplocin forrestii</em>, has demonstrated a wide range of medical benefits, including cardiotonic, anticancer, anti-inflammatory, and wound healing properties. Nevertheless, the effects of periplocin on IVDD remain unexplored.</div></div><div><h3>Objective</h3><div>Our study explores the mechanism of action and the potential target of periplocin in mitigating IVDD pathology.</div></div><div><h3>Methods</h3><div>Rat models of IVDD were established using acupuncture, and the affected discs underwent analysis via Safranin O-Fast Green (S-O) and Hematoxylin and Eosin (H&amp;E) staining. Nucleus pulposus cells (NPCs) were harvested from IVDD patients and experimental animals for examination. A variety of techniques, including Western blot analysis, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) assay, immunofluorescence staining, Alcian Blue staining and Immunohistochemistry (IHC) staining, were utilized to evaluate inflammation-related proteins, mRNAs and the ECM metabolism. In order to ascertain the potential protein targets of periplocin, the binding site of periplocin to LRP4 was elucidated through the utilisation of molecular docking experiments. Subsequently, the expression of low-density lipoprotein receptor-related protein 4 (LRP4) in NPCs was modified through the use of small interfering RNA (siRNA) knockdown and overexpression vectors, which were employed for the purposes of target validation.</div></div><div><h3>Results</h3><div>We conclude from the present study that periplocin alleviates the progression of IVDD mainly through the following aspects: periplocin inhibits TNF-α-induced inflammatory; periplocin reduces matrix degradation; periplocin promotes matrix anabolism and regulates metabolic homeostasis. Moreover, the present study demonstrates that LRP4 is involved as a potential target in the multiple pathways mentioned above to protect the intervertebral disc.</div></div><div><h3>Conclusion</h3><div>Our research suggests that periplocin may serve as a promising treatment for IVDD, offering anti-inflammatory benefits, preventing ECM degradation, and promoting ECM anabolism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156885"},"PeriodicalIF":6.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147798","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":"Multi-omics analysis reveals Angelica sinensis-Carthamus tinctorius herb pair ameliorates diabetic retinopathy comorbid with depressive symptoms via the gut-eye-brain axis","authors":"Rui Shen ,&nbsp;Wenjuan Zhao ,&nbsp;Yuting Wang ,&nbsp;Jesslyn Sukamto ,&nbsp;Guanyi Li ,&nbsp;Xinping Yang ,&nbsp;Xijier Qiaolongbatu ,&nbsp;Feng Qian ,&nbsp;Yun Liao ,&nbsp;Zhenghua Wu","doi":"10.1016/j.phymed.2025.156874","DOIUrl":"10.1016/j.phymed.2025.156874","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic retinopathy (DR) comorbid with depressive symptoms represents a significant public health challenge. The limitations of monotherapeutic approaches and the complex interplay between DR and depression highlight the need for comprehensive, integrated treatment strategies.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the therapeutic efficacy and underlying mechanisms of the <em>Angelica sinensis-Carthamus tinctorius</em> herb pair (ACHP) in addressing DR comorbid with depressive symptoms, utilizing an integrative multi-omics approach.</div></div><div><h3>Methods</h3><div>The chemical composition of ACHP was characterized using UPLC-MS. A DR mouse model exhibiting depressive-like behaviors was established through streptozotocin induction and long-term social isolation. The therapeutic effects and mechanisms of ACHP were evaluated using immunofluorescence, qRT-PCR, ELISA, non-targeted metabolomics, and 16S rRNA sequencing. Correlation analysis was conducted to elucidate the relationships among gut and ocular microbiota, serum metabolites, and clinical indices related to DR and depressive symptoms.</div></div><div><h3>Results</h3><div>ACHP treatment significantly alleviated hyperglycemia, retinal thinning, and depressive-like behaviors in the model mice. Multi-omics analysis revealed that ACHP restored gut microbiota balance by increasing beneficial <em>Lactobacillus</em> and reducing pathogenic genera such as <em>Dubosiella</em> and <em>Faecalibaculum</em>, while also reshaping ocular microbiota by suppressing pro-inflammatory <em>Achromobacter</em> and <em>Pseudomonas</em>. ACHP enhanced intestinal barrier integrity through upregulation of occludin, ZO-1 and MUC-2 and attenuated systemic and neuroinflammatory responses by reducing levels of LPS, TNF-α, IL-6, and IL-1β. Metabolomic profiling revealed that ACHP normalized glycerophospholipid metabolism—crucial for reducing inflammation and oxidative stress—specifically by inhibiting PLA2 and COX-2 while upregulating PPARγ. Correlation network analysis further emphasized the interactions among gut/ocular microbiota, inflammatory markers, and metabolites, highlighting the central role of the gut-eye-brain axis.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that ACHP alleviates DR-depression comorbidity by synergistically targeting microbial dysbiosis, metabolic dysregulation, and inflammatory cascades across the gut-eye-brain axis. This study provides a novel, holistic therapeutic strategy rooted in traditional Chinese medicine, offering new insights into treating complex comorbid conditions.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156874"},"PeriodicalIF":6.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177813","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":"Chemoproteomics reveals Ailanthone directly binds to PKM2 to inhibit the progression of Hepatocellular carcinoma","authors":"Cheng Lin ,&nbsp;Yue Wan ,&nbsp;Qiang Huo ,&nbsp;Dachuan Liu ,&nbsp;Xinhua Liu ,&nbsp;Hao Liu ,&nbsp;Yixuan Zhang ,&nbsp;Xiu Cheng","doi":"10.1016/j.phymed.2025.156886","DOIUrl":"10.1016/j.phymed.2025.156886","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular Carcinoma (HCC) is a widely recognized aggressive tumor, owing primarily to its high recurrence and metastasis risk. On the other hand, Ailanthone (AIL), a natural plant derivative, has demonstrated diverse pharmacological properties and a capacity to induce cell death among other mechanisms. Consequently, it could be employed to suppress HCC proliferation. Nonetheless, AIL’s precise targets and mechanisms of action in inhibiting HCC cell growth remain unclear, forming the basis of this study.</div></div><div><h3>Purpose</h3><div>To investigate the role and molecular mechanisms of AIL in inducing SMMC-7721 cell apoptosis and identify its key action targets.</div></div><div><h3>Methods</h3><div>First, the potential pathways and targets of AIL-induced cell death were identified via transcriptomics sequencing analyses. The impact of AIL on HCC cell growth was then evaluated both in vivo and in vitro, with the underlying mechanisms validated further. Finally, molecular docking, Molecular Dynamics (MD) simulation techniques, and Surface Plasmon Resonance (SPR) experiments were employed to elucidate AIL’s binding target.</div></div><div><h3>Results</h3><div>Our findings revealed that AIL could inhibit Pyruvate Kinase M2 (PKM2) expression, thus suppressing the aerobic glycolysis level of HCC cells. Mechanistically, AIL induced SMMC-7721 cell apoptosis via the PKM2/HSP90/HIF-1α signaling pathway. Furthermore, molecular docking, MD simulation, and SPR experiments confirmed AIL’s direct binding to PKM2. Specifically, AIL formed hydrogen bonds with PKM2 residues Lys311B, Leu353B, and Asp354A, accompanied by hydrophobic interactions with Phe26A/B and Leu353B.</div></div><div><h3>Conclusion</h3><div>By binding directly to PKM2, AIL exerts anti-tumor effects in SMMC-7721 cells, with glycolysis inhibition via PKM2/HSP90/HIF-1α signaling axis suppression as the potential mechanism, which could be leveraged in HCC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156886"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194840","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":"The promoting effect of high-fat diet-induced trained immunity on ulcerative colitis and the mechanism of the therapeutic effect of Dahuang Mudan Decoction","authors":"Pengcheng Li ,&nbsp;Rui Xu ,&nbsp;Hongxu Chen,&nbsp;Shuiling Cao,&nbsp;Xueqian Xie,&nbsp;Bo Xu,&nbsp;Yunliang Chen,&nbsp;Xuting Xie,&nbsp;Caiyi Yang,&nbsp;Qing Wang,&nbsp;Xia Luo,&nbsp;Lian Zhou","doi":"10.1016/j.phymed.2025.156893","DOIUrl":"10.1016/j.phymed.2025.156893","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a chronic inflammatory disease driven by intestinal immune imbalance. In addition, its pathogenesis includes environment, genetics, microbiota, genes, and diet. Epidemiological and related studies have shown that a high-fat diet habit can promote the progression of UC. The trained immunity induced by a high-fat diet is a key factor in the occurrence and development of chronic inflammatory diseases. As a chronic inflammatory disease, the research on how the trained immunity induced by a high-fat diet promotes the progression of UC is still unclear. Previous studies have shown that Dahuang Mudan Decoction can effectively alleviate the progression of UC, but whether its mechanism of action can also inhibit trained immunity is not clear.</div></div><div><h3>Methods</h3><div>To explore the promoting effect of trained immunity induced by a high-fat diet on UC, in this study, mice were fed a high-fat diet for 4 weeks and then modeled with 2 % DSS. Subsequently, by transplanting the bone marrow of a high-fat diet, it was repeatedly verified that a high-fat diet can promote the progression of UC through trained immunity. Then, to explore the therapeutic effect of Dahuang Mudan Decoction (DMD) and its mechanism, the above-mentioned model was intervened with DMD (125, 250, 500mg/kg). By transplanting the bone marrow of a high-fat diet and intervening with DMD, it was repeatedly verified that DMD can alleviate UC promoted by a high-fat diet by inhibiting trained immunity.</div></div><div><h3>Results</h3><div>The results of this study showed that the intervention of a high-fat diet promoted the progression of UC, aggravated the disease-related indicators of UC, promoted the damage of the colonic mucosal structure, reduced the expression of colonic mucin tight junction proteins, increased the number of bone marrow hematopoietic stem and progenitor cells (HSPCs), granulocyte-monocyte progenitor cells (GMPs), splenic monocytes, and colonic macrophages; promoted the expression of colonic inflammatory factors (IL-6, TNF-α). After transplanting the bone marrow intervention with a high-fat diet can promote the progression of UC, which is consistent with the trend of the above indicators. After the intervention of DMD, the above indicators were alleviated, and the subsequent transplantation of the bone marrow from a high-fat diet intervened with DMD can effectively alleviate the UC-related symptoms.</div></div><div><h3>Conclusion</h3><div>A high-fat diet promotes the progression of UC disease by promoting trained immunity and increasing the proportion of bone marrow HSPCs and GMPs, thereby increasing the proportion of splenic monocytes, the number of colonic tissue macrophages, and the level of inflammatory factors. DMD can alleviate the inflammatory response of UC mice intervened with a high-fat diet by inhibiting bone marrow trained immunity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156893"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178124","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}