Journal of ethnopharmacology最新文献

{"title":"Exploration of scientific connotation of “Yin-Jing” medical properties of Cyathula officinalis via potentiating therapeutic effect, guidance and targetability","authors":"Hong-Xiang Jiang ,&nbsp;Jun-Hong Chai ,&nbsp;Lan Zhou ,&nbsp;Xue Gao ,&nbsp;Xue-Qing Liu ,&nbsp;Wen-Fei Wang ,&nbsp;Jun Liang ,&nbsp;Hai-Xue Kuang ,&nbsp;Yong-Gang Xia","doi":"10.1016/j.jep.2025.119629","DOIUrl":"10.1016/j.jep.2025.119629","url":null,"abstract":"<div><h3>Ethnic pharmacological relevance</h3><div>“<em>Cyathula officinalis</em> Kuan (COK)” has the effect of “guiding the drug downward” and can enhance the efficacy of formula, e.g., Shentong Zhuyu Decoction (STZYD). However, there is currently no scientific basis on COK to guide drugs to target organs in STZYD.</div></div><div><h3>Aim of the study</h3><div>The main objective of this study was to unclose the scientific connotations of the Yin-Jing medicinal properties of COK using molecular biology and modern chemical methods.</div></div><div><h3>Materials and methods</h3><div>A rat model of adjuvant arthritis was established. The optimal dose of STZYD was determined by observing a series of indicators, and the therapeutic effects of STZYD and [STZYD - COK] were compared. The water decoction of COK was divided into five fragments (i.e., Fr. A-E) by macroporous adsorption resin and alcohol deposition methods. The Fr. A-E were further characterized by a combination of multiple chromatographic and spectral techniques. The potentiating therapeutic effects, guidance and targetability tests were used to evaluate “Yin-Jing” function by compatible combination of other drugs using pharmacological indicators, pharmacokinetics, high-performance liquid chromatography (HPLC) and small animal live imaging (SALI) techniques.</div></div><div><h3>Results</h3><div>The optimal dose of STZYD was confirmed to be 1 × dose and COK increased the efficacy of [STZYD - COK]. The results of chemical characterization showed that the main components of Fr. A-E were polysaccharide, fructooligosaccharide and small M_w fructan, saponins and flavonoid glycosides, steroidal ketones, organic acids esters, respectively. Pharmacological experiments showed that Fr. A, Fr. B and Fr. E were attributed to potentiate therapeutic effects. Guidance assays showed that Fr. B enhanced drug distribution and uptake in the kidneys, joints and cells. Targetability assays further confirmed that Fr. B had apparent targetability toward the joints and kidneys rather than other organs and tissues.</div></div><div><h3>Conclusions</h3><div>This study for the first time combined potentiating therapeutic effects, guidance and targeting evaluation system, and identified Fr. B as the pharmacodynamic material basis of COK's Yin-Jing medicinal properties.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119629"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614951","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":"Shuxuetong injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal","authors":"Jinfeng Shang ,&nbsp;Guijinfeng Huang ,&nbsp;Bohong Wang ,&nbsp;Jingyi Wang ,&nbsp;Wanting Wei ,&nbsp;Yiran Cui ,&nbsp;Xin Liu","doi":"10.1016/j.jep.2025.119618","DOIUrl":"10.1016/j.jep.2025.119618","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Acute ischemic stroke (AIS) is an important cause of death and disability in the world. Based on the blood stasis syndrome of stroke, Shuxuetong Injection (SXT) is a representative prescription for the treatment of AIS, which extracted by modern technology from <em>Whitmania pigra</em> Whitman (Shuizhi) and <em>Pheretima aspergillum</em> E.Perrier (Dilong).</div></div><div><h3>Aim of the study</h3><div>This study is in order to examine whether SXT regulates pyroptosis in AIS via Cluster of Differentiation 44 (CD44)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/gasdermin D (GSDMD) signal.</div></div><div><h3>Materials and methods</h3><div>The rats were randomly divided into sham group, model (transient middle cerebral artery occlusion, 24 h) group, SXT low-dose group (0.27 mL/kg), SXT medium-dose group (0.54 mL/kg), SXT high-dose group (1.08 mL/kg) and positive drug group (edaravone injection, 1.35 mL/kg). Transient middle cerebral artery occlusion (tMCAO, 24 h) model of rats was set up. Neurological deficit score, tetrazolium red staining, hematoxylin-eosin staining, and Nissl staining were used to observe and screen out the optimal dosage for improving AIS. Mechanism research indicators included transmission electron microscopy and Western blot. Adeno-associated virus (AAV)-CD44 and small interfering RNA (siRNA) of CD44 were used for knocking down the CD44 expression level to verify whether SXT could resist pyroptosis through CD44. The oxygen and glucose deprivation/re-oxygenation (OGD/R, 24 h) model of PC12 cells was used for in vitro pharmacological validation. Molecular docking, cellular thermal shift assay and drug affinity responsive target stability were employed to assess the binding affinity of critical components for the CD44 protein.</div></div><div><h3>Results</h3><div>SXT conspicuously mitigated the neurological function scores and cerebral infarct volume in tMCAO rats, thereby safeguarding nerve cells. In vitro, SXT not only enhanced the viability of PC12 cells subjected to OGD/R but also mitigated cellular swelling and inflammatory infiltration. The optimal dose was 1.08 mL/kg (rats) or 72.56 mg/mL (PC12 cells). SXT reduced pyroptosis and inflammation in tMCAO rats and OGD/R cells by decreasing the expression levels of GSDMD-N, NLRP3 and CD44. In addition, after knocking down the expression level of CD44 by using AAV-CD44 and siRNA-CD44, it was found that the pyroptosis of AIS intervened by SXT was closely related to the CD44/NLRP3/GSDMD signal. The pivotal constituent of SXT, xanthine, exhibited pronounced binding affinity towards the CD44 protein, thereby demonstrating the capacity to stabilize this molecular target.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that Shuxuetong Injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119618"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614989","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":"Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism","authors":"Zeru Zhang ,&nbsp;Yuxin Luo ,&nbsp;Hanwen Zhang ,&nbsp;Zhi Zeng,&nbsp;Weijian Zheng,&nbsp;Yuquan Zhao,&nbsp;Yixin Huang,&nbsp;Liuhong Shen","doi":"10.1016/j.jep.2025.119593","DOIUrl":"10.1016/j.jep.2025.119593","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Placenta is a kind of traditional Chinese medicine, known as “Ziheche”. The role of cow placental peptides (CPP) in delaying liver aging has been reported, and in-depth exploration of the specific regulatory mechanisms is of great significance for the recycling and utilization of CPP and the development of natural anti-aging drugs.</div></div><div><h3>Aim of the study</h3><div>To investigate the protective effects and mechanisms of CPP on liver aging induced by D-galactose (D-gal) in mice from the perspective of mitochondrial energy metabolism.</div></div><div><h3>Methods</h3><div>An aging model was induced in mice using D-gal. The body weight and liver index of mice were measured, followed by staining and electron microscopy to observe liver morphology and aging markers. Reactive oxygen species (ROS) levels and antioxidant-related indicators were assessed, and mitochondrial function was evaluated. Finally, changes and mechanisms in liver transcriptomics and targeted mitochondrial energy metabolomics were analyzed and integrated to elucidate the regulatory pathways through which CPP delays liver aging.</div></div><div><h3>Results</h3><div>CPP improved liver structural damage, oxidative stress, and mitochondrial dysfunction induced by D-galactose in aging mice. It increased the final body weight and liver index, alleviated hepatocyte swelling and degeneration, enhanced liver antioxidant capacity, and restored normal mitochondrial morphology and function. The combined analysis of targeted mitochondrial energy metabolomics and liver transcriptomics revealed that CPP directly or indirectly regulated mitochondrial energy metabolism and delayed aging by influencing the cAMP signaling pathway, PI3K-Akt signaling pathway, oxidative phosphorylation, and other pathways, thereby modulating related genes and metabolites.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119593"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597135","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 network pharmacology and untargeted metabolomics reveals Changpu San's antidepressant mechanisms via tryptophan metabolism","authors":"Fangrui Xiang ,&nbsp;Lin Hu ,&nbsp;Shengqi Zhang,&nbsp;Pengcheng Lv,&nbsp;Guihua Wei,&nbsp;Zhiyong Yan","doi":"10.1016/j.jep.2025.119590","DOIUrl":"10.1016/j.jep.2025.119590","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Changpu San (CPS) is a traditional Chinese medicine (TCM) formula historically used to treat symptoms resembling depression. However, its antidepressant effects and underlying mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate CPS's antidepressant effects and elucidate its mechanisms by combining network pharmacology with untargeted metabolomics.</div></div><div><h3>Materials and methods</h3><div>A chronic unpredictable mild stress (CUMS) mouse model was used to assess CPS's antidepressant effects via behavioral tests and body weight monitoring. By integrating network pharmacology and untargeted metabolomics, both based on UPLC-Q-Exactive-Orbitrap-MS for CPS chemical profiling and serum metabolite analysis, a key pathway was identified. This pathway was validated through UPLC-QQQ-MS/MS and ELISA by measuring relevant biomarkers, while its association with colonic microbiota was further investigated using 16S rDNA sequencing.</div></div><div><h3>Results</h3><div>CPS alleviated depression-like behaviors in CUMS mice. A total of 140 compounds were identified in CPS, revealing 140 core targets related to depression. Metabolomics analysis identified 42 serum metabolites significantly altered in CUMS mice, with tryptophan metabolism emerging as a shared pathway across both approaches. Experimental validation showed CPS partially reversed tryptophan metabolism dysregulation, significantly increasing tryptophan levels and reducing kynurenine levels in the brain. Moreover, CPS modulated the colonic microbiota, with key genera such as <em>Prevotella</em> and <em>Bacillus</em> showing correlations with tryptophan metabolism and inflammation.</div></div><div><h3>Conclusion</h3><div>CPS shows promise as an effective antidepressant, potentially through modulating tryptophan metabolism and reshaping colonic microbiota. This study provides valuable insights into its mechanisms and offers a methodological reference for researching other TCM formulas.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119590"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597136","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":"Effects of excessive Platycodon grandiflorus root on gut microbiota and host co-metabolism in mice","authors":"Shasha Han ,&nbsp;Zichen Luo ,&nbsp;Shihang Bao ,&nbsp;Zihan Xiao ,&nbsp;Weichen Xu ,&nbsp;Tong Xie ,&nbsp;Chen Shi ,&nbsp;Jin Wang ,&nbsp;Jinjun Shan","doi":"10.1016/j.jep.2025.119577","DOIUrl":"10.1016/j.jep.2025.119577","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Platycodon grandiflorus</em> root, is a widely used herb in East Asia for treating respiratory diseases, but research on its oral safety is limited.</div></div><div><h3>Aim of the study</h3><div>This study examines the potential adverse gastrointestinal reactions resulting from excessive consumption of <em>Platycodon grandiflorus</em> root (PR) and its effects on gut microbiota and host co-metabolism.</div></div><div><h3>Materials and methods</h3><div>This study evaluated the effects of different doses (1.5, 4.5, and 7.5 g/kg/day) of PR on ICR mice through gavage. Select the 7.5 g/kg/day dosage group and the control group to assess intestinal morphology and conduct histopathological studies. Examine inflammation-related factors and tight junction proteins using WB, qPCR, and ELISA. Additionally, perform 16S rDNA sequencing and metabolomic analyses to evaluate changes in gut microbiota and endogenous metabolites. Finally, the clearance of gut microbiota with antibiotics, the effects of excessive PR on mice were investigated.</div></div><div><h3>Results</h3><div>Excessive intake of PR can lead to mortality in mice, as well as symptoms such as intestinal flatulence and slowed intestinal transit, suggesting the occurrence of chronic intestinal pseudo-obstruction accompanied by endotoxemia. It altered both α-diversity and β-diversity in the gut microbiota of mice, with increased relative abundances of Pseudomonadota, Verrucomicrobiota, <em>Escherichia-Shigella</em>, <em>Akkermansia</em>, <em>Bacteroides</em>, and <em>Klebsiella</em>, closely linked to intestinal obstruction and bacterial overgrowth. Excessive intake of PR also resulted in metabolic disturbances in mice, particularly in the levels of metabolites such as bate-hydroxybutyrate, 5,6-dihydrouracil, uridine, isoleucine, mannitol, bate-alanine, L-cysteine, L-tyrosine, and orotic acid, which may provide insights into the side effects associated with excessive consumption of PR. Clearing the gut microbiota significantly mitigated adverse effects on the intestines and restored metabolite levels.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that excessive PR induces gut microbiota and metabolic disruption in normal mice, with the overgrowth of Gram-negative bacteria releasing LPS that impair smooth muscle contraction, leading to adverse effects such as chronic intestinal pseudo-obstruction.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119577"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585817","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":"Sphenocentrum jollyanum (Pierre) aqueous leaf extract demonstrates anti-inflammatory and mitochondrial-restorative influences while modulating apoptosis in streptozotocin-induced diabetic rats","authors":"Oladele Olufemi Omoyajowo ,&nbsp;Olubunmi Bolanle Ajayi ,&nbsp;John Oludele Olanlokun ,&nbsp;Oluwadamilare Oluwaseun Ajayi ,&nbsp;Yemisi Rufina Alli Smith","doi":"10.1016/j.jep.2025.119605","DOIUrl":"10.1016/j.jep.2025.119605","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Sphenocentrum jollyanum</em> (Pierre) is a medicinal plant native to West African countries, especially Nigeria and Ghana. The leaf <em>of S. jollyanum is a</em> traditional therapy for diabetes, erectile dysfunction, gastrointestinal disorders, and malaria. However, there is a paucity of information on the mitochondrial-restorative and apoptotic-modulating properties of <em>S. jollyanum</em> leaf.</div></div><div><h3>Aim of the study</h3><div>The anti-inflammatory, apoptotic-modulating, and mitochondrial-restorative effects of <em>S. jollyanum</em> were studied using diabetic Wistar albino rats induced with streptozotocin.</div></div><div><h3>Methods</h3><div>A high-fat diet (HFD) and a single dose injection of 10 mg/kg of streptozotocin (STZ) were used to induce type-2 diabetes model. Thirty-six (36) rats were randomly assigned into six groups as follows: Group 1 (normal diet + normal saline), Group 2 (HFD + 50 mg/kg STZ), Group 3 (HFD + 50 mg/kg STZ + 10 mg/kg glibenclamide), Group 4 (HFD + 50 mg/kg STZ + 50 mg/kg of <em>S. jollyanum</em> extract), Group 5 (HFD + 50 mg/kg STZ + 100 mg/kg of <em>S. jollyanum</em> extract), Group 6 (HFD + 50 mg/kg STZ + 200 mg/kg of <em>S. jollyanum</em> extract). Glucose levels (fasting) were monitored in the rats at a 48-h interval. After experimental treatment for 28 days, blood was collected via cardiac puncture into plain bottles. After differential centrifugation, serum was extracted into plain bottles for assessment of insulin, caspases 3 and 9 activity, as well as IL-1β, IL-6, CRP, and TNF-α levels. Liver mitochondria were isolated for mitochondrial ATPase activity, lipid peroxidation and mitochondrial permeability while liver and pancreatic tissues were prepared for histopathology using standard laboratory procedures.</div></div><div><h3>Results</h3><div>Induction of the Wistar rats with 50 mg/kg of streptozotocin increased fasting glucose, caspase 3, caspase 9, IL-1β, IL-6, TNF-α, CRP, troponin I, as well as increased mitochondrial permeability, mitochondrial lipid peroxidation, and mitochondrial ATPase activity significantly compared to the normoglycemic group and glibenclamide-treated group. This was also accompanied by pathological lesions in the liver and pancreas. Administration of <em>S. jollyanum</em> aqueous leaf extract significantly decreased mitochondrial ATPase activity, mitochondrial lipid peroxidation, caspase 3 and caspase 9 activity, and mitochondrial permeability, fasting blood glucose, IL-1β, IL-6, TNF-α, CRP, and troponin I levels in the diabetic rats, while significantly boosting serum insulin content (p &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div><em>S. jollyanum</em> aqueous leaf demonstrates anti-inflammatory, mitochondrial-protective and apoptotic-modulating influences while reversing hepatic and pancreatic damage in diabetic Wistar rats.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119605"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597053","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":"Desmodium caudatum (Thunb.) DC. extract attenuates hyperuricemia-induced renal fibrosis via modulating TGF-β1 pathway and uric acid transporters: Evidence from in vitro and in vivo studies","authors":"Hui-Hsuan Lin ,&nbsp;Yu-Hsuan Liang ,&nbsp;Charng-Cherng Chyau ,&nbsp;Chiao-Yun Tseng ,&nbsp;Jun-Quan Zhang ,&nbsp;Jing-Hsien Chen","doi":"10.1016/j.jep.2025.119609","DOIUrl":"10.1016/j.jep.2025.119609","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Desmodium caudatum</em> (Thunb.) DC., a traditional Chinese medicinal herb, has been used to treat conditions such as rheumatic back pain, diarrhea, jaundice-related hepatitis, and abscesses; it also serves as an anthelmintic. The extract of <em>Desmodium caudatum</em> (Thunb.) DC. (DCE) is also known for its antioxidant and anti-inflammatory properties. However, its impact on kidney fibrosis remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study investigated whether DCE can alleviate hyperuricemia-induced kidney fibrosis by modulating the transforming growth factor-β1 (TGF-β1) pathway, activating epithelial-mesenchymal transition (EMT), and regulating uric acid transporters.</div></div><div><h3>Materials and methods</h3><div>NRK52E cells were exposed to uric acid (UA) followed by DCE and isovitexin (IV) for 24 h. Cell damage was assessed using an Oxidative Stress Kit, ELISA, Gelatin Zymography, and Western blotting. In parallel, adenine-induced C57BL/6 mice received DCE and IV treatment for 11 weeks. After sacrifice, renal injury was assessed through histopathological examination and protein expression analysis of fibrosis markers, EMT indicators, and uric acid transporters.</div></div><div><h3>Results</h3><div>DCE reduced reactive oxygen species (ROS) accumulation in uric acid-induced NRK52E cells and inhibited EMT by suppressing TGF-β1 and Slug while restoring E-cadherin expression. DCE treatment reduced fibrosis-related proteins (CTGF, collagen I, fibronectin, and α-SMA) in UA-treated cells and modulated uric acid transporters by increasing ABCG2 and OAT3 while decreasing URAT1 and GLUT9. In adenine-induced hyperuricemic C57BL/6 mice, DCE administration reduced serum uric acid levels and xanthine oxidase activity. Histological analysis showed that DCE attenuated renal fibrosis through decreased glomerular atrophy, reduced collagen deposition, and diminished α-SMA and fibronectin expression.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that DCE exerts protective benefits against hyperuricemia-induced renal fibrosis. The potential mechanism may involve suppressing the TGF-β1 signaling pathway and regulating the uric acid transporter, thereby mitigating kidney injury.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119609"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597132","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":"Sodium aescinate induces hepatotoxicity through apoptosis and ferroptosis by inhibiting the Nrf2/CTH pathway","authors":"Xin Zheng,&nbsp;Xinyi Tang,&nbsp;Yinan Xu,&nbsp;Haiyan Zhu,&nbsp;Lianwei Zhong,&nbsp;Chen Chen,&nbsp;Jiajun Cui,&nbsp;Jie Zhou","doi":"10.1016/j.jep.2025.119608","DOIUrl":"10.1016/j.jep.2025.119608","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The seed of <em>Aesculus wilsonii</em> Rehd., also known as Suoluozi in China, is a traditional Chinese herb included in the Pharmacopoeia of China (2020). Sodium aescinate (SA) is derived from the <em>Aesculus wilsonii</em> Rehd.’s seeds and is extensively used in clinical practice.</div></div><div><h3>Aim of the study</h3><div>The study investigated the involvement of the Nrf2/CTH pathway in SA-induced hepatotoxicity and explored potential strategies for alleviating SA-induced liver damage.</div></div><div><h3>Materials and methods</h3><div>The ICR mice and AML12 mouse hepatocytes were exposed to SA. The levels of Fe²⁺, cysteine (Cys), glutathione (GSH), hydrogen sulfide (H₂S), ROS, lipid peroxides and caspase-3 activity were assessed. The effects of SA on signaling pathways related to ferroptosis and apoptosis were examined. Furthermore, genetic modification or agonists of Nrf2 and CTH were co-treated with SA.</div></div><div><h3>Results</h3><div>SA triggered ferroptosis and apoptosis in AML12 cells and mouse livers, characterized by a decline in Cys, GSH, and H₂S levels, as well as accumulation of Fe²⁺, ROS and lipid peroxides, mitochondrial dysfunction, and chromatin condensation. SA decreased Nrf2, CTH, and Bcl-2 levels, elevated Bax levels, and activated caspase-9/3. Overexpression of Nrf2 or CTH, or NAC supplementation alleviated SA-induced ferroptosis by upregulating Cys and GSH levels. Overexpression of Nrf2 or CTH, or NaHS supplementation increased H₂S levels, which reduced the interaction between p616-Drp1 and VDAC1 by enhancing Drp1 S-sulfenylation, thereby alleviating SA-induced mitochondrial-dependent apoptosis. Furthermore, DMF or Met mitigated SA-induced hepatotoxicity by activating the Nrf2/CTH pathway.</div></div><div><h3>Conclusions</h3><div>SA triggers oxidative stress, mitochondrial dysfunction, apoptosis, and ferroptosis, ultimately leading to liver damage by suppressing the Nrf2/CTH pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119608"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597140","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":"Pharmacodynamic components and molecular mechanism of Gastrodia elata Blume in treating hypertension: Absorbed components, network pharmacology analysis, molecular docking and in vivo experimental verification","authors":"Yun Li ,&nbsp;Xiaofei Yu ,&nbsp;Yezhi Liu ,&nbsp;Shuxin Miao ,&nbsp;Xiaoqian Liu ,&nbsp;Zhimin Wang ,&nbsp;Honglei Zhou","doi":"10.1016/j.jep.2025.119583","DOIUrl":"10.1016/j.jep.2025.119583","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Rhizome of &lt;em&gt;Gastrodia elata&lt;/em&gt; Blume (RGE) is a valuable traditional Chinese Medicine (TCM) in the clinical practice. &lt;em&gt;The Compendium of Materia Medica&lt;/em&gt; records that RGE has the effect of flatting liver wind out. It has sedative, analgesic, hypnotic, anticonvulsant, anti-hypertensive, anti-myocardial ischemia, anti-arrhythmic and anti-platelet aggregation effects. RGE is often used to relieve and treat vertigo, headache, hypertension, convulsions, and epilepsy in TCM clinic for thousands of years. Accumulated evidences have suggested that hypertension disease is related to the renin-angiotensin-aldosterone system (RAAS) disturbance. However, the potential pharmacodynamic components and anti-hypertensive mechanisms of RGE are unclear now.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;The active component and mechanism of RGE in treating hypertension were elucidated to strengthen the quality control and development of anti-hypertensive drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The anti-hypertensive active components of RGE were analyzed by multi-dimensional qualitative analysis method including ethanol extract, &lt;em&gt;in-vitro&lt;/em&gt; intestinal absorption, &lt;em&gt;in-vivo&lt;/em&gt; plasma. The ultra high performance liquid chromatography-mass spectrometry (UPLC-Q-Exactive MS/MS) analysis technology was adopted to identify these components. Network pharmacology was applied to predicted anti-hypertensive active components, target proteins and pathways. Molecular docking was used to evaluate the potential molecular binding modes between 68 components and nine proteins. Spontaneously hypertensive rats (SHR) model was adopted to evaluate the activity of reducing systolic and diastolic blood pressure (SBP and DBP). Levels of renin, angiotcnsin II (Ang II) and aldosterone (ALD) in serum were determined by Elisa kit. Immunohistochemical were adopted to compare the changes of Ang II receptor 1 (AT1R) protein levels in SHR model and RGE groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The multi-dimensional components qualitative analysis method of RGE was established. The results showed that 79, 70 and 30 components were identified in RGE ethanol extract, &lt;em&gt;in-vitro&lt;/em&gt; intestinal absorption and &lt;em&gt;in-vivo&lt;/em&gt; plasma, respectively. These components were mainly parishins, nucleosides, amino acids, phenolic acids, flavonoids, organic acids et al. Network pharmacology results showed that anti-hypertensive active components were nucleosides and organic acids. It was speculated that RGE could exert its anti-hypertensive effect by regulating aldosterone-regulated sodium reabsorption, renin-angiotensin system pathways and related target proteins. Molecular docking results showed that 21 components including parishins, nucleosides and phenolic acids were potential active components of anti-hypertensive. Taking together, parishin A, B, E, C, D, adenosine, N&lt;sup&gt;6&lt;/sup&gt;-(4-hydroxybenzyl) adenosine, guanos","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119583"},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585892","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":"DPHC from Alpinia officinarum Hance specifically modulates the function of CENPU in the cell cycle and apoptosis to ameliorate hepatocellular carcinoma","authors":"Zhe Zhu ,&nbsp;Xiuxia Lian ,&nbsp;Jicheng Hu ,&nbsp;Zhe Wang ,&nbsp;Yinghong Zhong ,&nbsp;Yuan Zhao ,&nbsp;Lu Lu ,&nbsp;Yipeng Pan ,&nbsp;Mingyan Zhou ,&nbsp;Jian Xu","doi":"10.1016/j.jep.2025.119598","DOIUrl":"10.1016/j.jep.2025.119598","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Alpinia officinarum</em> Hance (<em>A</em>. <em>officinarum</em>), a perennial herb used in the treatment of digestive system cancers, holds significant value for the Li people of Hainan as a traditional Chinese medicine. (R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC), a diarylheptanoid component is derived from <em>A</em>. <em>officinarum</em>. Diarylheptanoids have demonstrated anti-proliferative effects on breast cancer cells, neuroblastoma cells, and other tumor cells. However, the pharmacological activity of DPHC in improving hepatocellular carcinoma (HCC) remains undefined.</div></div><div><h3>Aim of the study</h3><div>To elucidate the anti-HCC effects of DPHC derived from <em>A</em>. <em>officinarum</em> and explore its underlying mechanistic pathways both in vivo and in vitro.</div></div><div><h3>Material and methods</h3><div>The effects of DPHC on HCC cell lines were evaluated in vitro using cell counting kit-8, EdU cell proliferation assays, a wound healing assay, a three-dimensional tumor spheroid model, and flow cytometry. The ability of DPHC to ameliorate HCC was assessed in vivo via a nude mouse subcutaneous xenograft tumor model, serum biochemical marker detection, and hematoxylin<em>-</em>eosin staining. The molecular mechanism of DPHC in HCC was elucidated through a combination of transcriptome sequencing, cell transfection, immunohistochemistry assay, immunofluorescence staining, quantitative reverse transcription-PCR, and western blot analysis.</div></div><div><h3>Results</h3><div>DPHC induced significant G0/G1 phase arrest and apoptosis in HepG2 and HCCLM3 cells while also markedly inhibiting tumor growth in nude mice. Mechanically, DPHC directly interacted with centromere-associated protein U (CENPU) to suppress its expression. The reduced expression of CENPU results in decreased interaction with the transcription factor E2F6, thereby affecting the transcriptional activity of the transcription factor E2F1. This subsequently inhibits the expression of downstream cell cycle factors (CCND1, CDK4, and CDK1) and increases apoptosis factors (Caspase 3 and Caspase 9).</div></div><div><h3>Conclusions</h3><div>DPHC from <em>A</em>. <em>officinarum</em> specifically modulates the function of CENPU in the cell cycle and apoptosis to ameliorate HCC. Our study revealed the anti-HCC effect and underlying mechanism of DPHC, offering new insights and potential targets for HCC treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119598"},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585815","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}