Journal of ethnopharmacology最新文献

{"title":"Achillea fragrantissima (Forssk.) Sch. Bip. essential oil inhibits the growth of pancreatic cancer cells via induction of necrosis, sub-G1 arrest, modulation of β-catenin/ERK signalling pathways and p38α MAPK, CDK2, EGFR inhibition","authors":"Mohammed Khaled Bin Break , Weiam Hussein , Dalal Alafnan , Haya O. Almutairi , Ahmed A. Katamesh , Maali D. Alshammari","doi":"10.1016/j.jep.2025.120201","DOIUrl":"10.1016/j.jep.2025.120201","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Achillea frag<em>rantissima</em> (Forssk.) Sch. Bip. is a medicinal plant that has been traditionally used in several Arab countries such as Egypt, Jordan and Saudi Arabia, for cancer treatment. Studies on the plant's extracts and essential oil showed that they exhibited cytotoxic activity against some cancer cells, however, the oil's activity was poorly studied; often involving MTT/SRB cell viability assays only without further mechanism of action studies.</div></div><div><h3>Aim of the study</h3><div>To study the anticancer potential of <em>Achillea fragrantissima</em> essential oil (AFEO), investigate its mechanism of action in detail for the first time and identify its chemical constituents.</div></div><div><h3>Materials and methods</h3><div><em>Achillea fragrantissima</em> was obtained from Hail, Saudi Arabia, while its essential oil was collected using a Clevenger apparatus. SRB assay was used to assess AFEO's cytotoxic activity against A549 (lung), HCT116 (colon) and PANC-1 (pancreatic) cancer cells, while cell-cycle and apoptosis assays were performed <em>via</em> flow cytometry. Protein expression was analysed <em>via</em> Western blotting, while GCMS was used to analyse AFEO's chemical composition. p38α MAPK, CDK2 and EGFR enzymatic assays were performed <em>via</em> the corresponding assay kits, and molecular docking was conducted using Maestro software.</div></div><div><h3>Results</h3><div>AFEO demonstrated its most potent activity against PANC-1 cells followed by HCT116 cells with IC<sub>50</sub> values of 63 μg/ml and 81 μg/ml, respectively, however, no significant activity was observed against A549 cells. The oil also showed lower toxicity towards healthy HSF cells and demonstrated higher selectivity for the cancer cells. Further studies against PANC-1 revealed that AFEO induced necrosis and sub-G1 phase arrest in the cells. Western blotting revealed that AFEO did not alter caspase-3 expression level, further confirming the lack of apoptosis induction in PANC-1 cells by the oil. Moreover, AFEO downregulated β-catenin expression and this is specifically desirable in the case of pancreatic cancer, however, it upregulated phosphorylated ERK (p-ERK) expression indicating ERK pathway activation. AFEO did not change phosphorylated Akt (p-Akt) and PTEN expression, indicating lack of effect on the Akt pathway. Furthermore, AFEO was found to potently inhibit enzymes related to the ERK pathway and cancer progression in general, with IC<sub>50</sub> values of 0.45 μg/ml, 0.23 μg/ml and 0.14 μg/ml against p38α MAPK, CDK2 and EGFR enzymes, respectively. GCMS analysis identified the major bioactive compounds as 3-thujanone (30.51 %), artemisia ketone (4.68 %), eucalyptol (2.57 %) and germacrene D (2.56 %). Finally, molecular docking studies predicted that 3-thujanone would primarily bind to and inhibit p38α MAPK and EGFR, while germacrene D would primarily inhibit CDK2 with binding energies of −7.","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120201"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491920","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":"In vivo, in vitro and in silico evaluation of Rumex nepalensis Spreng. and its active phytoconstituent (Chrysophanol) in gastrointestinal disorders","authors":"Neelum Gul Qazi , Arif-ullah Khan , Aslam Khan , Fawad Ali , Amber Mahmood Minhas , Arooj Mohsin Alvi","doi":"10.1016/j.jep.2025.120177","DOIUrl":"10.1016/j.jep.2025.120177","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Rumex nepalensis</em> Spreng<em>,</em> is widely used in traditional medicine for management of gastrointestinal (GIT) disorder, including ulcer, diarrhea and inflammation. However, limited scientific evidence exists to validate its traditional use in GIT disorders.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the <em>anti-Helicobacter pylori</em> and gastroprotective activities of the crude extract of <em>Rumex nepalensis</em> (Rn.Cr), its fractions [aqueous (Rn.Aq), n-hexane (Rn.n-Hex), ethyl acetate (Rn.ETAC)] and its major phytoconstituent, Chrysophanol.</div></div><div><h3>Methods</h3><div>Pharmacological activities of <em>Rumex nepalensis</em> crude extract, its fractions and chrysophanol were assessed using ethanol-induced gastric ulcer and castor oil induced diarrheal in rodents. Antioxidant activity was assessed by measuring levels of reduced glutathione (GSH), glutathione S-transferase (GST), catalase (CAT), and lipid peroxidation (LPO) in gastric tissue homogenates and anti-inflammatory effects were evaluated by quantifying pro-inflammatory biomarkers, including interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB). <em>Anti-H. pylori</em> activity was assessed through a disk diffusion assay, while molecular docking and simulation studies elucidated the interaction of chrysophanol with H<sup>+</sup>/K<sup>+</sup>-ATPase and TLR4 pathways. Acute toxicity was assessed by OECD Guideline 425, using a single-dose oral toxicity test in rats to determine the safety profile. Hematological (e.g., RBC, WBC, Hb, and platelet count) and biochemical parameters (e.g., ALT, AST, ALP, urea, and creatinine) were analyzed using standard automated hematology analyzers and biochemical kits to evaluate systemic toxicity and organ function.</div></div><div><h3>Results</h3><div>The plant extracts exhibited a dose-dependent antidiarrheal effect and significantly decreased intestinal fluid secretion in mice, while also reducing the distance traversed by charcoal in a gastrointestinal transit model in rats. Both spontaneous and K<sup>+</sup> (80 mM)-induced contractions in rabbit jejunum preparations were relaxed by extracts and in a concentration-dependent manner. Rn.Cr, Rn.ETAC and verapamil were relatively effective against K<sup>+</sup>-induced contractions and shifted the Ca<sup>2+</sup> concentration-response curves (CRCs) to the right like that of verapamil. The isoprenaline-induced inhibitory CRCs were moved to the left by Rn.n-Hex similar to papaverine. Rn.ETAC and Rn.n-Hex were effective against <em>H.pylori</em>. Chrysophanol and extracts have an inhibitory impact on H<sup>+</sup>/K<sup>+</sup>-ATPase. ELISA shows decreased expression of inflammatory markers, including COX-2, TNF-α, IL-8 and p-NFƙB. H<sup>+</sup>/K<sup>+</sup>-ATPase mRNA levels decline confirmed by RT-PCR. Biochemical and hematological tests, along with kidney","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120177"},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491305","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":"Huoluo Xiaoling Pellet improves ischemic stroke by regulating metabolic disorders through integrins and ICAM1","authors":"Xingfang Zhang ,&nbsp;Min Bai ,&nbsp;Tianlong Liu ,&nbsp;Yucheng Liao ,&nbsp;Jiping Yu ,&nbsp;Mengye Zhang ,&nbsp;Qiudong Zhang ,&nbsp;Xinliang Xu ,&nbsp;Yi Ding","doi":"10.1016/j.jep.2025.120178","DOIUrl":"10.1016/j.jep.2025.120178","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Ischemic stroke (IS) is primarily caused by the stenosis or occlusion of cerebral arteries, leading to ischemic injury in brain tissue. Huoluo Xiaoling Pellet (HLXLP) is known for its efficacy in promoting blood circulation and removing blood stasis.</div></div><div><h3>Aim of this study</h3><div>This study aims to investigate the therapeutic effects of HLXLP on IS and elucidate its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>Initially, we characterized the components of HLXLP that were absorbed into the bloodstream. Subsequently, potential therapeutic targets and active ingredients were explored through network pharmacology and analysis of GEO transcriptomic datasets. Further validation was conducted via compound similarity comparison, molecular docking, molecular dynamics simulation, and <em>in vivo</em> experiments. Finally, metabolomics was utilized to investigate the cerebral metabolic changes influenced by HLXLP.</div></div><div><h3>Results</h3><div>A total of 39 components of HLXLP were identified in the blood. Bioinformatics analysis revealed that ITGB1, ITGB2, ITGB3, ITGAL, and ICAM1 were identified as potential targets, which were confirmed in <em>in vivo</em> experiments. Metabolomics analysis indicated that HLXLP may alleviate the progression of IS by modulating the TCA cycle, cholesterol biosynthesis, and tryptophan metabolism in the brain.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that HLXLP exerts its anti-IS effects by acting on targets such as ITGB1, ITGB2, ITGB3, ITGAL, and ICAM1 and modulating the TCA cycle, cholesterol biosynthesis, and tryptophan metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120178"},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481608","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":"Establishing identifiable characteristic fingerprints of mulberry leaves: Integrating chemical composition and bioactivity through machine learning","authors":"Che Chun Lin ,&nbsp;San Yuan Wang ,&nbsp;Kowit Yu Chong ,&nbsp;Vinh Tuyen T. Le ,&nbsp;Yi Ying Lin ,&nbsp;Lih Geeng Chen ,&nbsp;Chia Jung Lee ,&nbsp;Ching Chiung Wang","doi":"10.1016/j.jep.2025.120186","DOIUrl":"10.1016/j.jep.2025.120186","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Mulberry leaves (Morus alba L.) are used in traditional Chinese medicine to clear the lungs and dispel wind-heat. Despite their common use, chemical reference substance rely solely on rutin, which may not reflect their full pharmacological potential.</div></div><div><h3>Aim of the study</h3><div>To develop a multicomponent quality evaluation strategy for mulberry leaves by integrating HPLC fingerprinting, chemometrics, and biological validation.</div></div><div><h3>Materials and methods</h3><div>Twenty-seven mulberry leaf samples were analyzed using HPLC. PCA, PLS-DA, and Pearson correlation were applied to identify quality markers. An artificial neural network (ANN) model was constructed based on 17 characteristic peaks. Anti-fibrotic effects were evaluated in bleomycin-induced pulmonary fibrosis mice.</div></div><div><h3>Results</h3><div>Based on the distribution of chemical reference substances contents in the 27 samples, the mulberry leaves could be categorized into high- and low-content groups, with 0.1 % rutin serving as the classification threshold. An ANN analysis of the HPLC fingerprint was then employed to establish a recognition model based on the full fingerprint, achieving a classification accuracy of 100 %. Rutin correlated with MMP-13 inhibition, and cryptochlorogenic acid with both MMP-13 and PAI-1 inhibition. <em>In vivo</em> studies demonstrated that qualified extracts of mulberry leaves reduced the progression of bleomycin-induced pulmonary fibrosis.</div></div><div><h3>Conclusions</h3><div>This study establishes a comprehensive and bioactivity-linked quality evaluation framework for mulberry leaves, aligning traditional knowledge with modern scientific assessment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120186"},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491306","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":"Inhibiting multidrug resistant Shigella flexneri using comparative genomics guided In vitro and In silico screening","authors":"Sarmishta Mukhopadhyay ,&nbsp;Fernando Berton Zanchi ,&nbsp;Gaurab Aditya Dhar ,&nbsp;Santanu Chakrabarti ,&nbsp;Sayak Ganguli","doi":"10.1016/j.jep.2025.120187","DOIUrl":"10.1016/j.jep.2025.120187","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Gram-negative bacterium <em>Shigella</em> is the most widely documented etiologic factor for diarrheal mortality in infants, contributing to 13.2 % of diarrheal episodes across the globe. The present surge in antibiotic resistance, increasing numbers of non-typeable strains, and the disparate regional distribution of multiple <em>Shigella</em> variants has rendered it obvious that novel therapeutic alternatives are desperately sought after to address the growing threat of shigellosis.</div></div><div><h3>Aim of the study</h3><div>In the present investigation, we have assessed the antibacterial properties of selected medicinal plants, against a naturally isolated, multidrug-resistant strain of <em>Shigella flexneri</em>, using different in-vitro susceptibility assays.</div></div><div><h3>Materials and methods</h3><div>We used virtual screening, molecular docking, and molecular dynamic simulation to quickly and accurately screen natural compounds derived from these plants for antibacterial agents. To further comprehend the antimicrobial mechanism of the herbal extracts and their active constituents against <em>Shigella flexneri</em>, a comparative transcriptome analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was undertaken to contrast and evaluate the differential patterns of gene expression between the treated and untreated populations.</div></div><div><h3>Results</h3><div>The findings deemed the two herbal extracts of <em>Psidium guajava</em> and <em>Scoparia dulcis</em> as a source of viable therapeutic candidates against the multi-drug-resistant strain.</div></div><div><h3>Conclusions</h3><div>The prospective active constituents, viz. 5-Hydroxy-1-isopropyl-6,6-dimethyl-5-phenyl-piperidin-2-one and limonene, and their corresponding therapeutic targets reported in this research, thus bring up the possibility of switching existing drugs with more potent phytopharmaceuticals for effectively controlling <em>Shigella</em> superbugs, awaiting further investigations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120187"},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481006","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 therapeutic effects and molecular mechanisms of total flavonoids of Abelmoschus manihot (L.) Medic in the treatment of IgA nephropathy based on WGCNA","authors":"Changqing Wen ,&nbsp;Hang Su ,&nbsp;Jiaxuan Li ,&nbsp;Jia Zou ,&nbsp;Mingxu Gong ,&nbsp;Fujiang Wang ,&nbsp;Haitao Ge","doi":"10.1016/j.jep.2025.120191","DOIUrl":"10.1016/j.jep.2025.120191","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>IgA nephropathy (IgAN) is characterized by the deposition of thylakoid Gd-IgA1 and progresses to kidney dysfunction and failure. Thousands of years ago, <em>Abelmoschus manihot (L.) Medic</em> has been used as a traditional Chinese medicine to treat kidney diseases. The total flavonoid (TFA) of <em>Abelmoschus manihot (L.) Medic</em> is the main active ingredient of the medicine, which is known to have therapeutic effects on kidney diseases. However, the mechanism of action is still not further explored.</div></div><div><h3>Aim of study</h3><div>We aim to reveal the targets and potential mechanisms of TFA through comprehensive proteomics and Weighted Gene Co-expression Network Analysis (WGCNA), and to provide new ideas for the treatment of IgAN.</div></div><div><h3>Materials and methods</h3><div>In this study, we constructed a model of IgA nephropathy in rats and evaluated the efficacy of TFA in the IgAN model by assessing renal function, renal Gd-IgA1/IgA and serum markers. Integrated proteomics and WGCNA analysis identified core targets associated with TFA, and target validation was performed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Kidney function (Scr, PCR, BUN) and serum markers (TGF-β1, TNF-α, BAFF, MCP-1) were significantly reduced after TFA treatment. Proteomics identified 2,757 differential expressed genes (DEGs). WGCNA highlighted four key modules associated with TFA effects. Six core targets (C1QBP, CYC1, Phab, VDAC2, CDH2, Dbn1) were validated by immunohistochemistry, confirming their roles in TFA renoprotection.</div></div><div><h3>Conclusion</h3><div>Induction of rat IgAN model, proteomics and WGCNA analyses demonstrated that TFA improves renal function, reduces histopathological damage and modulates inflammation. These findings further elucidate the treatment mechanism of TFA and provide new insights into the treatment of IgA nephropathy.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120191"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365103","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":"Qishentaohong granules alleviate heart failure by modulating mitochondrial fission and mitophagy balance","authors":"Jialin Jin ,&nbsp;Yuxuan Li ,&nbsp;Sinai Li ,&nbsp;Dong Li ,&nbsp;Jing Liu ,&nbsp;Jinjin Lu ,&nbsp;Qiaozhi Dong ,&nbsp;Qian Wu ,&nbsp;Yan Li ,&nbsp;Qian Lin","doi":"10.1016/j.jep.2025.120190","DOIUrl":"10.1016/j.jep.2025.120190","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Heart failure (HF) remains a critical challenge in cardiovascular therapeutics. Qishentaohong granules (QSTH), formulated under the traditional Chinese medicine Qi-Blood theory, have demonstrated clinical efficacy in HF management through randomized controlled trials. However, their precise mechanisms of action remain unclear.</div></div><div><h3>Objective</h3><div>To investigate the mechanistic role of QSTH in regulating mitochondrial homeostasis for HF amelioration.</div></div><div><h3>Methods</h3><div>HF murine models and cardiomyocyte hypertrophy models were developed for QSTH intervention. Cardiac function and structural integrity were assessed via echocardiography and histopathological staining. Mitochondrial fission (FIS1, MFF) and mitophagy markers (p62, LC3B, PARKIN) were quantified by Western blot in vivo and in vitro. Mitochondrial ultrastructure was analyzed using transmission electron microscopy (TEM) and two-photon excitation polarized fluorescence (TEPF) microscopy. In vitro mechanistic studies employed pathway inhibitors and <em>Pink1</em> siRNA to validate regulatory pathways. Molecular alterations were evaluated through Western blot, qRT-PCR, and immunofluorescence.</div></div><div><h3>Results</h3><div>QSTH ameliorated myocardial pathology and cardiac function in HF mice through suppression of mitochondrial fission proteins (FIS1, MFF) and activation of mitophagy, indicated by elevated LC3B and PARKIN expression coupled with reduced p62 levels. TEPF microscopy revealed enhanced mitochondrial network integrity in QSTH-treated cardiomyocytes. In vitro, QSTH attenuated hypertrophy by modulating reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis. Mechanistically, QSTH activated PINK1 expression/phosphorylation, inhibited CaMKIIδ T287 phosphorylation, and regulated DRP1 S616 phosphorylation, thereby balancing mitochondrial fission-mitophagy dynamics via the CaMKIIδ-DRP1-PINK1 pathway.</div></div><div><h3>Conclusion</h3><div>QSTH restores cardiomyocyte mitochondrial homeostasis through modulation of the CaMKIIδ-DRP1-PINK1 pathway, effectively attenuating hypertrophy, improving cardiac function, and reducing fibrosis in HF models.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120190"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475506","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":"Mechanistic analysis of anti-prostate cancer and toxicity-reducing effects of bufadienolides extracts: Comparative efficacy and safety with isolated bioactive compounds","authors":"Rong Lin ,&nbsp;Qingmei Ye ,&nbsp;Qi He ,&nbsp;Dong-Seon Kim ,&nbsp;Daihong Chen ,&nbsp;Lu Jin ,&nbsp;Wenguang Wang ,&nbsp;Juan Li","doi":"10.1016/j.jep.2025.120182","DOIUrl":"10.1016/j.jep.2025.120182","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Bufonis Venenum, a traditional ethnic drug, has shown potential efficacy in managing cancer, cardiovascular diseases, pain, and inflammation. Bufadienolides, its primary active constituents, exhibit potent antitumor activity.</div></div><div><h3>Aim of the study</h3><div>This study investigates the anti-prostate cancer and toxicity-reducing properties of bufadienolides extracts.</div></div><div><h3>Materials and methods</h3><div>The bufadienolides compounds were characterized using LC-MS/MS. Prostate cancer cells, normal prostate cells, and H9c2 cells were treated with bufadienolides extracts and its main compounds. Cell proliferation and migration were evaluated using MTT and scratch assays, while apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry and the DCFH-DA fluorescence probe. Additionally, transcriptome-metabolomics analysis was employed to elucidate regulatory pathways, which were further verified by qRT-PCR and Western blot (WB). Bufadienolides' toxicity and antitumor effects were assessed using acute toxicity assays and an H22 tumor-bearing mouse model.</div></div><div><h3>Results</h3><div>Apart from eight bufadienolides compounds, the formation of aggregates, such as dimers of monomeric compounds, was identified within the extracts. Bufadienolides extracts and its major components, bufalin and resibufogenin, significantly inhibited prostate cancer cell proliferation and migration, induced apoptosis, and promoted ROS production. They modulated key biological processes, including IL-17, TNF, MAPK, and mTOR signaling, lipid metabolism, and pantothenate and CoA biosynthesis. Notably, extracts exhibited superior efficacy compared to bufalin and resibufogenin in both <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Conclusion</h3><div>The combined action of multiple bufadienolides in the extract may enhance their overall efficacy and safety, highlighting their potential as therapeutic agent for prostate cancer.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120182"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365092","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":"Study on the chemical composition, zebrafish toxicity and anti-inflammatory activity of Ecklonia kurome","authors":"Xueyan Li ,&nbsp;Zhaoyi Yang ,&nbsp;Denghui Yu,&nbsp;Yiwen Zhang,&nbsp;Zhixin Shen,&nbsp;Yansong Meng,&nbsp;Yuling Ding,&nbsp;Yong Li","doi":"10.1016/j.jep.2025.120171","DOIUrl":"10.1016/j.jep.2025.120171","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Inflammation is an important physiological process that serves as the host's defense mechanism against tissue damage, stress, or oxidative stress. As a traditional medicinal and edible plant, <em>Ecklonia kurome</em> (EK) is used to treat galls and scrofula, which is now known as lymphatic tuberculosis and lymphadenitis, but the specific effective medicinal ingredients of EK are not clear, and further exploration is needed for its anti-inflammatory activity.</div></div><div><h3>Aim of study</h3><div>This study aims to extract, isolate and purify EK, and investigate its pharmacological effects, in order to explore the chemical composition, toxicity and anti-inflammatory activity of EK.</div></div><div><h3>Materials and method</h3><div>Silica gel, Sephadex gel (LH-20) and other column chromatography methods were used to separate and purify the ethanol extract of EK, and the zebrafish embryo model was used to conduct toxicity evaluation research. The anti-inflammatory activity of monomer compounds was predicted and verified based on molecular docking technology. The lipopolysaccharide induced cell inflammation model was tested to detect NO, reactive oxygen species (ROS), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) Study the expression level of indicators and investigate the therapeutic effect of EK on inflammatory cells.</div></div><div><h3>Results</h3><div>Eight compounds were isolated from EK, namely Ishigoside (<strong>1</strong>), Squalene (<strong>2</strong>), <em>δ</em>-tocopherol (<strong>3</strong>), Phytol (<strong>4</strong>), Di - (2-ethylhexyl) phthalate (<strong>5</strong>), 1,3-dilinoloylglycerol (<strong>6</strong>), Fuchosterol (<strong>7</strong>), and Mannitol (<strong>8</strong>). Compound <strong>1</strong> was isolated from EK for the first time, while compounds <strong>2</strong>–<strong>6</strong> were reported for the first time.; The toxicity test results showed that compounds <strong>1</strong>–<strong>8</strong> did not produce zebrafish embryonic developmental toxicity at 12.5, 25, 50, and 100 μ M; The molecular docking results showed that the new compound had a good binding effect with inflammatory factors; The anti-inflammatory experiment results of RAW264.7 cells showed that compounds <strong>1</strong>–<strong>8</strong> did not produce cytotoxicity at 3, 10, 30, and 100 nM, but significantly increased cell viability and inhibited NO in cells, The levels of ROS, IL-6, IL-1β, TNF-α, and PGE2.</div></div><div><h3>Conclusion</h3><div>The research results indicate that compounds derived from EK can significantly reduce the expression levels of inflammatory cytokines and are safe, suggesting that EK has certain application prospects and can be further developed and utilized.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120171"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469997","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":"Xiaoyaosan alleviates chronic psychological stress-induced TH17/Treg imbalance via modulation of the FKBP5/NF-κB axis","authors":"Yi Zhang ,&nbsp;Xiao-Ru Luo ,&nbsp;Yu-Hang Zhou ,&nbsp;Qian-Yin Xue ,&nbsp;Shu-Ya Wu ,&nbsp;Jing-Yu Xu ,&nbsp;Guo-Hui Li ,&nbsp;Bu-Ping Liu ,&nbsp;Ming-Jia Zhang ,&nbsp;Guang-Dong Tong ,&nbsp;Hai-Qing Ao ,&nbsp;Mian-Mian Liao","doi":"10.1016/j.jep.2025.120184","DOIUrl":"10.1016/j.jep.2025.120184","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xiaoyaosan (XYS), a classical herbal formulation indicated for “depression syndrome”, can improve chronic stress-related mood disorders and immune disorders through multi-target modulation of inflammatory mediators, although its precise mechanism in regulating Th17/Treg balance remains to be clarified.</div></div><div><h3>Aim of the study</h3><div>This study aims to elucidate the regulatory impact of XYS on the peripheral Th17/Treg immunological imbalance generated by chronic psychological stress through modulation of the FKBP5/NF-κB signaling pathway, thereby establishing a mechanistic foundation for developing innovative interventions with dual stress-adaptogenic and immunoregulatory properties.</div></div><div><h3>Materials and methods</h3><div>FKBP5 knockout (FKBP5^−/−) and C57BL/6 mice underwent a 35-day chronic unpredictable mild stress (CUMS) paradigm. C57BL/6 mice were subsequently treated with XYS (1.61, 3.22, and 6.44 g/kg/d), fluoxetine (3 mg/kg/d). Behavioral phenotyping included the Open Field Test (OFT), Tail Suspension Test (TST), Forced Swimming Test (FST) and Sucrose preference test (SPT). Serum inflammatory cytokines (IL-17A, IL-23, IL-10, TNF-α) measured by enzyme-linked immunosorbent test (ELISA). Splenic Th17/Treg subset ratios were analyzed using multicolor flow cytometry. Western blotting evaluated FKBP5 expression and NF-κB pathway dynamics (IκB-α degradation, P65 nuclear translocation). UPLC-HRMS-based phytochemical profiling coupled with molecular docking elucidated XYS-FKBP5 interactions. FKBP5/IKKα/β complex formation was validated through confocal immunofluorescence (IF) colocalization and reciprocal co-immunoprecipitation (CO-IP) assays.</div></div><div><h3>Results</h3><div>CUMS mice exhibited significant depression-like behaviors and hippocampal neuronal damage, concomitant with elevated serum corticosterone levels and Th17/Treg immune dysregulation. Medium- and high-dose XYS interventions substantially ameliorated these behavioral abnormalities, reversed hippocampal pathological alterations, suppressed pro-inflammatory responses, and rectified Th17/Treg imbalance. Crucially, XYS exerted therapeutic effects through targeted suppression of FKBP5-IKK complex interaction, effectively blocking NF-κB nuclear translocation, thereby restoring Th17/Treg homeostasis.</div></div><div><h3>Conclusion</h3><div>XYS ameliorates chronic psychological stress-induced Th17/Treg immune imbalance through FKBP5-targeted suppression of NF-κB hyperactivation. This multicomponent synergistic mechanism establishes a novel therapeutic strategy for stress-associated inflammatory comorbidities, particularly depression with immune dysregulation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120184"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475507","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}