Journal of ethnopharmacology最新文献

{"title":"Gancao decoction ameliorated senecionine-induced Hepatic Sinusoidal Obstruction Syndrome in mice by inhibiting NET formation and senecionine bioactivation in liver","authors":"Shuang Zhang ,&nbsp;Dongming Yan ,&nbsp;Si Cheng ,&nbsp;Jingyi Jin ,&nbsp;Jiamin Cui ,&nbsp;Chenghai Liu ,&nbsp;Yue Li ,&nbsp;Furong Qiu","doi":"10.1016/j.jep.2026.121356","DOIUrl":"10.1016/j.jep.2026.121356","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In China, pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS) accounts for approximately 50.0-88.6% of all HSOS cases, primarily resulting from inadvertent ingestion of <em>Gynura japonica</em> (Thunb.) Juel. (Tǔ sān qī). <em>Glycyrrhiza uralensis</em> Fisch. (Gān cǎo), a classical hepatoprotective herb in Traditional Chinese Medicine (TCM), has recently demonstrated significant protective effects against PA-induced HSOS in murine models. However, its underlying mechanisms remain poorly understood.</div></div><div><h3>Aim of study</h3><div>This study aimed to assess the therapeutic efficacy of Gancao decoction (GCD) and elucidate its underlying mechanisms in PA-induced HSOS.</div></div><div><h3>Materials and methods</h3><div>HSOS was induced in mice by senecionine (SEN), followed by treatment with GCD or enoxaparin (ENO, positive control). Histopathological and therapeutic efficacy was assessed by histopathological examination and serum biochemical analyses. Neutrophil depletion was employed to investigate the contribution of neutrophil extracellular traps (NETs) to the protective effects of GCD. Transcriptomic analysis was performed to identify potential targets of GCD. Mechanistic studies were investigated using quantitative real-time PCR (qPCR), Western blotting (WB), and immunofluorescence (IF). In addition, the inhibitory effect of GCD on SEN bioactivation was evaluated using human liver microsomes (HLMs).</div></div><div><h3>Results</h3><div>GCD improved serum biochemistry and hepatic histopathology in SEN-induced HSOS mice. Mechanistically, GCD suppressed intrahepatic neutrophil chemotaxis, thereby reducing NET formation and alleviating immunothrombosis. Furthermore, GCD inhibited the hepatic formation of dehydropyrrolizidine (DHP), the reactive metabolite responsible for SEN-induced HSOS.</div></div><div><h3>Conclusion</h3><div>GCD attenuated SEN-induced HSOS through dual mechanisms: (1) suppression of chemokine-driven neutrophil chemotaxis, leading to reduced NET formation and immunothrombosis; (2) inhibiting of SEN bioactivation. These findings provide mechanistic support for the ethnopharmacological use of Gancao in PA-HSOS and highlight its potential for clinical translation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121356"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics and metabolomics demonstrate that Taohe Chengqi decoction alleviates sepsis-associated acute lung injury by modulating immunometabolism","authors":"Zuming Li ,&nbsp;Jiankun Chen ,&nbsp;Ming Gao ,&nbsp;Kao Gan ,&nbsp;Jian Xu ,&nbsp;Wanhua Huo ,&nbsp;Simin Pan ,&nbsp;Yunqi Kong ,&nbsp;Xiaoya Li ,&nbsp;Jiqiang Li ,&nbsp;Yue Lu ,&nbsp;Yuntao Liu ,&nbsp;Rongyuan Yang","doi":"10.1016/j.jep.2026.121283","DOIUrl":"10.1016/j.jep.2026.121283","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The clinical treatment of sepsis-associated acute lung injury (SA-ALI) is a major issue faced by critical care medicine. Taohe Chengqi decoction (THCQ), a formulation rooted in traditional Chinese medicine, exhibits potential therapeutic efficacy in the management of sepsis-associated complications. However, the precise mechanisms underlying its effects remain to be comprehensively elucidated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the potential immunometabolism mechanisms of THCQ in the treatment of SA-ALI.</div></div><div><h3>Materials and methods</h3><div>The study first established an LPS-induced SA-ALI mouse model to verify the pharmacological effects of THCQ. Non-targeted metabolomics was employed to explore the metabolic pathways regulated by THCQ, including OPLS-DA, differential metabolites, and pathway enrichment. Single-cell transcriptomics was employed to investigate the immune microenvironment regulated by THCQ, including gene expression analysis, pathway enrichment, and cellular communication. Finally, the pharmacological mechanism of THCQ was validated by Western blotting, RT-PCR, ELISA, and flow cytometry.</div></div><div><h3>Results</h3><div>Integrating single-cell transcriptomics and untargeted metabolomics analysis revealed that THCQ improved the alveolar-capillary barrier by inhibiting glycolysis. Specifically, THCQ ameliorated pathological changes in alveolar epithelial cells and microvascular endothelial cells, and inhibited the pro-inflammatory response of damage-responsive alveolar fibroblasts. THCQ reversed the pathological mechanism of Il1b⁺alveolar macrophages and NK cells by regulating glycolysis, and demonstrated the potential to regulate the phenotype of Fth1⁺neutrophils and Prok2⁺neutrophils, reshaping the immune microenvironment during SA-ALI.</div></div><div><h3>Conclusion</h3><div>This study reveals the immunometabolism mechanism of THCQ treatment for SA-ALI through single-cell transcriptomics and metabolomics analysis, laying the groundwork for subsequent fundamental research and clinical applications. These findings are based on one batch of THCQ, so further studies are necessary to confirm consistent effects across multiple batches for reproducibility and clinical relevance.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121283"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive improvement and hippocampal BDNF/GFAP alterations by Schinus molle essential oil in a rat model of scopolamine-induced amnesia","authors":"Umut İrfan Üçel ,&nbsp;Ümmühan Kandemi̇r ,&nbsp;Cevşen Yazici ,&nbsp;Öznur Bi̇lgi̇n ,&nbsp;Nazlı Turan Yücel ,&nbsp;Temel Özek ,&nbsp;Ümide Demi̇r Özkay ,&nbsp;Gökalp İşcan ,&nbsp;Özgür Devrim Can","doi":"10.1016/j.jep.2026.121309","DOIUrl":"10.1016/j.jep.2026.121309","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Schinus molle</em> L. (Anacardiaceae) has been traditionally used for conditions related to the nervous system and emotional well-being, often through aromatic preparations. However, its cognition-specific effects have not yet been investigated.</div></div><div><h3>Aim of the study</h3><div>To assess the cognitive effects of the fruit-derived essential oil of <em>Schinus molle</em> L. (SMEO), administered via oral and inhalation routes, in a rat model of scopolamine-induced amnesia.</div></div><div><h3>Materials and methods</h3><div>SMEO was obtained by hydrodistillation and characterised by GC–MS/GC–FID. Amnesic rats received SMEO for 14 days by inhalation (1% or 3%) or oral gavage (100 or 200 mg/kg). Cognition was assessed by Morris water maze (MWM), passive avoidance (PA), and novel object recognition (NOR) tests; locomotion was measured by activity-meter. Hippocampal BDNF and GFAP immunoreactivity were assessed by immunohistochemistry.</div></div><div><h3>Results</h3><div>SMEO was dominated by α-phellandrene (48.7%). Scopolamine impaired cognition, whereas SMEO attenuated deficits with efficacy comparable to piracetam. Key behavioural and immunohistochemical findings (main omnibus statistical effects) were as follows: In the MWM, treatment and time effects on escape latency were significant (both p &lt; 0.001), and probe performance improved (p &lt; 0.001). PA retention was restored (p &lt; 0.001) and the NOR index improved (p &lt; 0.001), without locomotor changes (all p &gt; 0.05). Scopolamine reduced hippocampal BDNF immunoreactivity in CA1 and DG (p &lt; 0.01) and CA3 (p &lt; 0.001), which was restored by SMEO via both routes. GFAP immunoreactivity was reduced in CA1/CA3/DG (all p &lt; 0.001) and was rescued selectively after inhalation.</div></div><div><h3>Conclusions</h3><div>These findings provide preclinical evidence consistent with an ethnopharmacological rationale for SMEO and support further translational work to clarify its relevance beyond this experimental paradigm.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121309"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid antidepressant effects of Aurantii Fructus are mediated by hypoxanthine-caspase-4 axis in CUMS mice","authors":"Chao Lu,&nbsp;Liyuan Tian,&nbsp;Zixuan Wei,&nbsp;Yiran Jiang,&nbsp;Mengqi Shao,&nbsp;Yaping Zhu,&nbsp;Lei Wu","doi":"10.1016/j.jep.2026.121330","DOIUrl":"10.1016/j.jep.2026.121330","url":null,"abstract":"<div><h3>Ethnopharmacological relevancy</h3><div>Aurantii Fructus (AF)is a traditional Chinese medicine historically used to regulate Qi and alleviate emotional distress, suggesting potential psychotropic effects. This study investigates its therapeutic value for depression based on this traditional indication.</div></div><div><h3>Aim of the study</h3><div>To evaluate the rapid antidepressant-like effect of a single acute dose of AF extract in a chronic unpredictable mild stress (CUMS) mouse model and elucidate its underlying molecular mechanisms through integrated transcriptomic and metabolomic analyses.</div></div><div><h3>Materials and methods</h3><div>AF flavonoid content was quantified by HPLC. Male mice underwent a 4-week CUMS protocol. A single oral dose of AF was administered 2 h prior to behavioral testing (NSF, TST, SPT, and OFT), with ketamine serving as a positive control. Hippocampal transcriptome analysis was performed by RNA sequencing, and serum metabolites were profiled via LC-MS in both positive and negative ion modes. Pearson correlation analysis assessed relationships between key targets and behavioral outcomes. Pathway involvement was functionally validated in a separate experiment using a hypoxanthine synthesis inhibitor.</div></div><div><h3>Results</h3><div>AF contained narirutin (1.32 mg/g), hesperidin (3.19 mg/g), neohesperidin (22.89 mg/g), naringenin (0.03 mg/g), and nobiletin (0.08 mg/g). Acute AF administration rapidly reversed CUMS-induced depressive-like behaviors, significantly decreasing latency to feed and increasing food consumption in the NSF test, reducing immobility time in the TST, and elevating sucrose preference in the SPT, without altering locomotor activity. Transcriptomic analysis revealed specific downregulation of hippocampal caspase-4 expression by AF. Metabolomic profiling showed AF normalized elevated serum hypoxanthine levels. Serum hypoxanthine levels negatively correlated with hippocampal caspase-4 expression and behavioral improvements, whereas caspase-4 expression positively correlated with behavioral deficits. Pharmacological inhibition of hypoxanthine synthesis abolished AF's antidepressant effects and prevented its normalization of hippocampal caspase-4, NF-κB, GDNF, and BDNF expression.</div></div><div><h3>Conclusions</h3><div>Acute AF produces rapid, ketamine-like antidepressant effects by targeting the hypoxanthine-caspase-4 pathway. This study reveals a novel purinergic mechanism underlying AF's traditional use for emotional disorders and offers a promising therapeutic strategy for rapid-acting antidepressant development.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121330"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in traditional Chinese medicine-mediated regulation of microglial metabolic reprogramming in neurological disease therapy","authors":"Zhenzhen Wu ,&nbsp;Fengyu Lv ,&nbsp;Siyu Shao ,&nbsp;Yongjun Chen ,&nbsp;Ning Weng ,&nbsp;Yucen Xia","doi":"10.1016/j.jep.2026.121355","DOIUrl":"10.1016/j.jep.2026.121355","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Neuroinflammation, driven by microglial metabolic reprogramming, underpins neurological diseases. Contrasting with the limitations of single-target therapies, TCM and acupuncture offer multi-targeted anti-inflammatory and antioxidant effects to modulate microglial activation, with TCM directly regulating microglial energy metabolism.</div></div><div><h3>Aim of the study</h3><div>This review aims to elucidate how TCM and acupuncture regulate microglial energy metabolism in neurological diseases, identify key metabolic enzymes and signaling pathways, and establish a scientific foundation for their translational applications.</div></div><div><h3>Materials and methods</h3><div>we systematically searched major scientific databases (PubMed, Web of Science, Sinomed, and CNKI) from January 2010 to December 2025 using predefined keywords including “TCM”, “acupuncture”, “microglia”, “glucose/lipid/amino acid metabolism”, and “neurological diseases” (e.g., Alzheimer's disease, depression). Our literature review focused on two main aspects: (1) direct mechanistic studies of TCM bioactive compounds and formulas on microglial energy metabolism; (2) related studies on acupuncture's effects on brain or astrocyte metabolism, providing indirect evidence for its potential effects on glial cell metabolism.</div></div><div><h3>Results</h3><div>TCM bioactive compounds and formulas regulate metabolic enzymes and pathways, correcting microglial metabolic disturbances. These interventions promote microglial polarization toward the anti-inflammatory M2 phenotype, reducing neuroinflammation and improving outcomes in neurological diseases. Acupuncture may modulate metabolic pathways in microglia, supporting its role as an auxiliary therapeutic modality in TCM.</div></div><div><h3>Conclusion</h3><div>TCM restores microglial metabolic homeostasis, enhancing M2 polarization and neuroprotection. These findings highlight TCM's potential for developing metabolism-immunity dual-target interventions for neurological diseases. Further research is needed to elucidate acupuncture's mechanisms and effects on microglial metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121355"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of non-targeted metabolomics and transcriptomics reveals the mechanistic rationale of Coptidis Rhizoma's cold property via systemic energy homeostasis and adaptive thermogenesis in mice","authors":"Ran Xie,&nbsp;Yuling Liu,&nbsp;Qi Song,&nbsp;Lixia Song,&nbsp;Jiameng Li,&nbsp;Yanmin Zhang,&nbsp;Jing Meng,&nbsp;Baokai Dou,&nbsp;Xiaoyu Hu,&nbsp;Lv Gao,&nbsp;Qinghe Zhao,&nbsp;Hairu Huo,&nbsp;Feng Sui","doi":"10.1016/j.jep.2026.121344","DOIUrl":"10.1016/j.jep.2026.121344","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.</div></div><div><h3>Aim of the study</h3><div>This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its “cold” property.</div></div><div><h3>Materials and methods</h3><div>A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out <em>via</em> MetaboAnalyst online database.</div></div><div><h3>Results</h3><div>The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.</div></div><div><h3>Conclusion</h3><div>CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the “cold” property of CR in TCM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121344"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model","authors":"A.D. de Beer ,&nbsp;W. Rudolph ,&nbsp;V. Maharaj ,&nbsp;V. Steenkamp ,&nbsp;M. Balmith ,&nbsp;W. Cordier","doi":"10.1016/j.jep.2026.121222","DOIUrl":"10.1016/j.jep.2026.121222","url":null,"abstract":"<div><h3>Introduction</h3><div>Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. <em>Polygala virgata</em> is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of <em>P. virgata</em> using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.</div></div><div><h3>Method</h3><div>Dried roots of <em>P. virgata</em> (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).</div></div><div><h3>Results</h3><div>Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p &lt; 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.</div></div><div><h3>Conclusion</h3><div><em>P. virgata</em> fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121222"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive evaluation of the anti-inflammatory potential of Cucurbita maxima leaf extract: LC–MS phytochemical profiling coupled with in vitro, in vivo, and in silico approaches","authors":"Hammadi Maroua ,&nbsp;Mohammed Larbi Benamor ,&nbsp;Yahia Bekkar ,&nbsp;Salah Neghmouche Nacer ,&nbsp;Elhafnaoui Lanez ,&nbsp;Ouafa Boudebia ,&nbsp;Housseyn Chaoua ,&nbsp;Aicha Adaika ,&nbsp;Lazhar Bechki ,&nbsp;Touhami Lanez ,&nbsp;Stefania Garzoli","doi":"10.1016/j.jep.2026.121267","DOIUrl":"10.1016/j.jep.2026.121267","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cucurbita maxima</em> (pumpkin) leaves have been traditionally used in folk medicine for the treatment of inflammation, fever, and oxidative stress–related disorders. However, scientific validation of these claims remains limited. This study aimed to evaluate the anti-inflammatory, antioxidant, and protective effects of <em>C. maxima</em> leaf aqueous extract and to elucidate its phytochemical composition and molecular mechanisms of action.</div></div><div><h3>Materials and methods</h3><div>The phytochemical profile of the aqueous extract was determined using UPLC–ESI–MS/MS analysis. In vivo anti-inflammatory activity was assessed in a benzylthiouracil-induced inflammation model by measuring white blood cell (WBC) counts, C-reactive protein (CRP) levels, and histopathological changes in liver and kidney tissues. In vitro anti-inflammatory potential was evaluated through the protein denaturation inhibition assay, using diclofenac as a reference. Pharmacokinetic and toxicity properties of major compounds were predicted using ADMET tools, while molecular docking studies were performed to evaluate interactions with COX-1 and COX-2 enzymes.</div></div><div><h3>Results</h3><div>UPLC–ESI–MS/MS analysis revealed a complex mixture of polyphenols, with caffeic acid (56.04%), rutin (9.25%), ferulic acid (8.79%), and myricetin-3-rhamnose (8.62%) as the main constituents. The extract significantly reduced inflammation by normalizing WBC counts (from 7.2 to 4.5 × 10⁹/L), lowering CRP levels (from 630 to 220 mg/L), and protecting liver and kidney tissues. The extract also inhibited protein denaturation in vitro (IC₅₀ = 2.976 mg/mL) compared to diclofenac (IC₅₀ = 0.718 mg/mL). Molecular docking revealed that major flavonoids exhibited strong binding affinities toward COX-1 and COX-2, often surpassing diclofenac, supported by stable hydrogen bonding and hydrophobic interactions. ADMET and toxicity predictions indicated good intestinal absorption for several major compounds, absence of predicted hepatotoxicity or skin sensitization, and generally low acute toxicity, with high predicted LD₅₀ values and no mutagenic risk for most constituents.</div></div><div><h3>Conclusion</h3><div>These findings support the traditional use of <em>C. maxima</em> leaves in folk medicine for the management of inflammation-related conditions, fever, and associated oxidative stress. Further isolation of the key active constituents and clinical evaluation are recommended to confirm their therapeutic efficacy.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121267"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overactivation of TRPV4 by toosendanin induces intracellular calcium overload and colonic toxicity","authors":"Hui Dai ,&nbsp;Qiao Liu ,&nbsp;Xin mei Zhang ,&nbsp;Jing cheng Zhang ,&nbsp;Fang zhou Yin ,&nbsp;Wu Yin","doi":"10.1016/j.jep.2026.121307","DOIUrl":"10.1016/j.jep.2026.121307","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Fructus Meliae Toosendan (FMT) is a widely utilized natural medicine across various traditional medical systems, with a long history of extensive application. However, excessive use of FMT may result in severe intestinal toxicity. The specific components responsible for this toxicity and the underlying mechanisms remain unclear.</div></div><div><h3>Materials and methods</h3><div>The compositional differences between FMT and stir-fried FMT (SFFMT) were identified using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Subsequently, bioinformatics analysis, molecular docking, kinetic modeling and microscale thermophoresis (MST) were employed to ascertain that toosendanin (TSN) targets intestinal transient receptor potential vanilloid receptor 4 (TRPV4). Calcium ion (Ca²⁺) fluorescent probes, flow cytometry, immunofluorescence analysis and western blotting were employed to assess the elevation of calcium ions induced by TSN, which subsequently resulted in intestinal barrier damage. Finally, H&amp;E staining, mouse endoscopy and immunofluorescence analysis confirmed that excessive oral administration of TSN leads to intestinal barrier damage in mice.</div></div><div><h3>Results</h3><div>Firstly, the content of TSN in SFFMT significantly decreased compared to that in FMT. Secondly, we present that TSN activates TRPV4, and that excessive TSN intake leads to elevated Ca²⁺ levels and overload in colonic epithelial cells, which induces acute colonic toxicity by damaging the colonic barrier. It has been demonstrated in mouse models that high doses of TSN induce colonic barrier damage.</div></div><div><h3>Conclusions</h3><div>Excessive TSN induces abnormal activation of TRPV4, leading to an elevation of intracellular calcium ions. This phenomenon is recognized as the primary cause of colonic toxicity associated with FMT.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121307"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine Cardiac Blood processed Kansui Radix alleviates PTZ-induced epileptic damage in mice via the bidirectional regulation of GABRA1 and cGMP/PKG signaling pathway","authors":"Jiali Cai ,&nbsp;Yaojian Zhang ,&nbsp;Mengyi Wu,&nbsp;Wenye Jiang,&nbsp;Tian Zhang,&nbsp;Bingyan Ma,&nbsp;Dijun Wang,&nbsp;Xueke Nie,&nbsp;Xiaojing Yan","doi":"10.1016/j.jep.2026.121313","DOIUrl":"10.1016/j.jep.2026.121313","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>According to Menghe Medical School, Porcine Cardiac Blood (PCB) enhances the upward distribution of medicinal substances throughout the body. Although both ancient and modern evidence suggest that PCB processed <em>Kansui Radix</em> (PCB-GS) has antiepileptic effects, its mechanisms for epilepsy remain unclear.</div></div><div><h3>Aim of the study</h3><div>To assess the therapeutic effects and mechanisms of PCB-GS in pentylenetetrazol (PTZ)-induced epileptic damage in mice.</div></div><div><h3>Materials and methods</h3><div>Quantitative analysis of chemical profiles of PCB-GS and <em>Kansui Radix</em> (GS) extracts was performed using UPLC-Q-TOF-MS/MS technology. Characterization of extracts was conducted via scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Ultraviolet spectrum. An acute epileptic model in mice induced by PTZ was established. Hippocampal proteomics and molecular biology techniques were employed to investigate the mechanisms by which PCB-GS treats epilepsy.</div></div><div><h3>Results</h3><div>Following PCB processing, the liposoluble components in GS increased, forming globular-like particles and altering UV spectral characteristics. PCB-GS alleviated PTZ-induced epileptic seizures, including reduced seizure frequency and severity, prolonged seizure latency, shortened total seizure duration, and suppression of spike counts. PCB-GS alleviated neuronal damage in the hippocampal dentate gyrus (DG), reduced the expression of the epilepsy marker c-Fos, and decreased microglial activation. Hippocampal proteomics identified the cGMP/PKG signaling pathway as a key mediator of PCB-GS effects. Western blot analysis showed that cGMP, p-PKG and p-VASP, levels increased significantly 1h after PTZ administration, then decreased markedly by 24h. PCB-GS modulates the cGMP/PKG signaling pathway by bidirectionally regulating the expression of the upstream GABRA1 protein, ultimately suppressing the elevation of downstream p-CREB and Cleaved caspase-3 protein levels.</div></div><div><h3>Conclusion</h3><div>PCB-GS protected against epileptic seizures via bidirectional modulation of the cGMP/PKG signaling axis through stabilization of GABRA1 expression, thereby suppressing p-CREB and Cleaved caspase-3.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121313"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}