Journal of ethnopharmacology最新文献

{"title":"Camellia japonica hyperoside exhibits anti-age-related macular degeneration effects in an ARPE-19 cell model by inhibiting apoptosis via JNK-Nrf2/HO-1 activation","authors":"Seung-Yub Song ,&nbsp;Duc Dat Le ,&nbsp;Mina Lee ,&nbsp;Seung-Sik Cho ,&nbsp;Dae-Hun Park","doi":"10.1016/j.jep.2026.121305","DOIUrl":"10.1016/j.jep.2026.121305","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Camellia japonica</em> is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.</div><div><em>Aim of the study</em>: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of <em>Camellia japonica</em> and to explore the underlying mechanisms using an ARPE-19 AMD cell model.</div></div><div><h3>Material and methods</h3><div>The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For <em>in vitro</em> evaluation of the anti-AMD effects, ARPE-19 cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30 μM A2E and 20 mW/cm² blue light treatment; Lutein, treatment with 25 μM lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150 μM hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.</div></div><div><h3>Results</h3><div>Hyperoside was nontoxic to ARPE-19 cells up to 150 μM. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19 cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.</div></div><div><h3>Conclusion</h3><div>We conclude that <em>C. japonica</em> hyperoside could be a promising anti-AMD drug.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121305"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142557","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":"Buyang Huanwu Decoction attenuates vascular aging by suppressing the pathway of neutrophil extracellular trap formation via modulation of the HMGB1/TLR4/p38 signaling pathway","authors":"Nan Xiao ,&nbsp;Jinsong Gao ,&nbsp;Yutong Yang ,&nbsp;Chenghui Li ,&nbsp;Xuejuan Shen ,&nbsp;Xiangyu Chen ,&nbsp;Xiaodie Chen ,&nbsp;Yanbin Pan ,&nbsp;Huiqun Huang ,&nbsp;Simin Yang ,&nbsp;Shuting Zeng ,&nbsp;Xiaodong Duan ,&nbsp;Yongan Deng ,&nbsp;Chengkai Chen ,&nbsp;Yixuan Huang ,&nbsp;Danping Huang ,&nbsp;Zunpeng Shu ,&nbsp;Li Zhang","doi":"10.1016/j.jep.2026.121315","DOIUrl":"10.1016/j.jep.2026.121315","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vascular aging is a significant driver of age-related cardiovascular diseases, in which the immune-inflammatory response driven by excessive formation of neutrophil extracellular traps (NETs) is a core process accelerating this progression. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine (TCM) formula widely used for treating cardio-cerebrovascular diseases, but whether it acts through modulating NET-driven vascular aging is unknown.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the mechanism by which BHD delays vascular aging, focusing on the NETs formation pathway.</div></div><div><h3>Materials and methods</h3><div>Based on a D-galactose-induced aging mouse model, this study focused on neutrophils and combined transcriptomics, network pharmacology and molecular biology methods to explore the mechanism of BHD in delaying vascular aging.</div></div><div><h3>Results</h3><div>The present study identified 23 major chemical constituents in BHD and demonstrated its efficacy in ameliorating aging phenotypes in a D-galactose-induced aging mouse model. BHD treatment significantly alleviated aortic structural degeneration, reduced oxidative stress and inflammatory cytokine levels, and downregulated key senescence markers including p16 and p21. Integrated multi-omics analysis implicated NET suppression as a primary mechanism underlying the anti-aging benefits of BHD. Both in vivo and in vitro experiments confirmed that BHD inhibits NETosis by modulating the HMGB1/TLR4/p38 signaling pathway, leading to reduced expression of critical NET components. Notably, HMGB1 overexpression partially reversed the inhibitory effects of BHD on NETosis, establishing HMGB1 as a key effector molecule.</div></div><div><h3>Conclusion</h3><div>For the first time, our findings unveil a novel mechanism whereby BHD alleviates vascular aging by modulating the immune microenvironment through inhibition of the HMGB1–TLR4–p38–NETs cascade. These findings provide a novel immunomodulatory perspective on BHD and highlight its potential as a holistic therapeutic strategy against vascular aging.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121315"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142575","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":"Tianwangbuxiandan decoction alleviates constipation and associated emotional disorders via regulating the brain-gut axis: Involving MAPK/ERK/JNK signaling pathways","authors":"Shaoliang Li ,&nbsp;Pengning Wu ,&nbsp;Yue Wang,&nbsp;Dehao Wang,&nbsp;Haihua Qian,&nbsp;Dan Zhang","doi":"10.1016/j.jep.2026.121308","DOIUrl":"10.1016/j.jep.2026.121308","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Tianwang Buxin Dan (TWBXD) is a classical Chinese formula traditionally prescribed to “nourish Yin, calm the mind and relieve bowel stagnation” in disorders characterized by heart-kidney disharmony, insomnia, anxiety, and constipation. However, the mechanistic basis associating its gut-regulating and emotion-modulating effects along the gut-brain axis remains unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate whether TWBXD ameliorates functional constipation comorbid with emotional disturbances by modulating mitogen-activated protein kinase/Extracellular Signal-Regulated Kinase/c-Jun N-terminal Kinase (MAPK/ERK/JNK) signaling, hypothalamic-pituitary-adrenal (HPA)-axis activity, and autophagy-related mitochondrial integrity in the colon and hippocampus.</div></div><div><h3>Materials and methods</h3><div>A diphenoxylate-induced rat model of functional constipation with anxiety/depression-like behavior was treated with low, medium, or high doses of TWBXD. Intestinal transit, fecal parameters, and distal colonic transit were also assessed. Emotional behaviors were evaluated using open-field and elevated plus-maze tests. Colonic and hippocampal histopathology and ultrastructure were examined using hematoxylin and eosin staining, Nissl staining, and transmission electron microscopy. Serum corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were measured using enzyme-linked immunosorbent assay. MAPK/ERK/JNK-related proteins and brain-derived neurotrophic factor (BDNF) were analyzed by Western blotting. The major chemical constituents of TWBXD were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC–MS/MS).</div></div><div><h3>Results</h3><div>TWBXD dose-dependently improved intestinal transit, fecal moisture, and body weight gain, and alleviated anxiety-/depression-like behaviors. TWBXD preserved colonic mucosal architecture and hippocampal neuronal integrity, mitigated mitochondrial swelling and excessive autophagic vacuole formation, downregulated colonic phosphorylated ERK (p-ERK), phosphorylated JNK, and phosphorylated p38, restored hippocampal BDNF expression while normalizing p-ERK levels, and reduced serum CRF, ACTH, and CORT levels.</div></div><div><h3>Conclusion</h3><div>TWBXD exerts multi-target therapeutic effects on functional constipation with emotional disturbances by suppressing MAPK/ERK/JNK overactivation, normalizing HPA-axis hyperactivity, and protecting mitochondrial structure and autophagy along the gut-brain axis, providing mechanistic support for its traditional use in gut-brain-related disorders.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121308"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137199","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":"Standardized alkali-treated Euglena gracilis β-glucan mitigates PM2.5-induced pulmonary and cerebral injury through NF-κB, NRF2, and CREB–BDNF–TrkB pathways","authors":"Ye-Lim You ,&nbsp;Ha-Jun Byun ,&nbsp;Jin-Young Jeon ,&nbsp;Bo-Ra Kim ,&nbsp;Ji Eun Hwang ,&nbsp;Jun Hee Lee ,&nbsp;Hyeon-Son Choi","doi":"10.1016/j.jep.2026.121276","DOIUrl":"10.1016/j.jep.2026.121276","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Euglena gracilis</em> has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury.</div></div><div><h3>Aim of the study</h3><div>To evaluate the protective effects of standardized alkali-treated <em>E. gracilis</em> β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung–brain axis.</div></div><div><h3>Materials and methods</h3><div>AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2–HO-1, and CREB–BDNF–TrkB pathways.</div></div><div><h3>Results</h3><div>AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood–brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2–HO-1, while enhancing the cerebral CREB–BDNF–TrkB neurotrophic pathway.</div></div><div><h3>Conclusions</h3><div>AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung–brain axis. These findings validate the potential of <em>E. gracilis</em>-derived β-glucan as a functional agent for preserving respiratory and neural health.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121276"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137590","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":"Phytochemical profiling, anti-virulence effects, and antibacterial mechanisms of Myrothamnus flabellifolius (Welw.) extracts","authors":"Mashilo Mash Matotoka,&nbsp;Talita Jessica Mnisi,&nbsp;Potsiso Letau Koma,&nbsp;Matsilane Lethabo Mashilo,&nbsp;Peter Masoko","doi":"10.1016/j.jep.2026.121342","DOIUrl":"10.1016/j.jep.2026.121342","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Myrothamnus flabellifolius,</em> the “resurrection plant,” traditionally used in southern Africa, shows strong potential for anti-virulence chemotherapy and for mitigating toxin-linked pathogenesis, reinforcing its enduring ethnomedicinal value.</div></div><div><h3>Aim of the study</h3><div>to investigate the phytochemical composition, antibiofilm, cytoprotective and anti-haemolytic effects, and potential antibacterial mechanisms of the extracts.</div></div><div><h3>Materials and methods</h3><div>Simultaneous extraction of plant material was done using hexane and aqueous acetone, followed by liquid-extraction of acetone extract. LC-MS was used for chemical profiling. Antioxidant activity was assessed. Haemolytic and cytoprotective activities were investigated against hydrogen peroxide and <em>β</em>-haemolytic pathogens. Antibacterial activity was assessed using broth micro-dilution, dehydrogenase and cell membrane disruption assays. Antibiofilm activity was investigated using the crystal violet, tetrazolium assays and evaluation of bacterial growth.</div></div><div><h3>Results</h3><div>Taxifolin, eriodyctiol, quercetin were identified in the ethyl acetate subfractions of the leaves (LEA) and stems (SEA) and phytosterols in the hexane fractions of the leaves (LH) and stem (SH). LEA and SEA exhibited strong antioxidant activity and provided significant protection of erythrocytes against oxidative and pathogen-induced haemolysis. LEA and SEA were active against <em>Pseudomonas aeruginosa</em> (MIC = 160 μg/mL), LH showed similar activity against <em>Staphylococcus aureus</em> (MIC = 160 μg/mL). The extracts disrupted the bacterial cell envelopes and inhibited dehydrogenase-linked metabolisms. Sub-MIC of LH, SH, and SEA significantly reduced biofilm formation in <em>P. aeruginosa</em> and <em>Streptococcus pyogenes</em>, despite exerting minimal effects on planktonic growth.</div></div><div><h3>Conclusion</h3><div><em>M. flabellifolius</em> shows strong multi-target antibacterial and sub-MIC antibiofilm activity, alongside notable antioxidant, cryoprotection and potential for addressing oxidative stress-linked ailments.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121342"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137597","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":"Elucidating the material basis and mechanism of Shegan Mahuang decoction in inhibiting influenza virus pneumonia based on UHPLC-HRMS, network pharmacology and experimental verification","authors":"Xin-Ye Du ,&nbsp;Lei Xu ,&nbsp;Dan Liu ,&nbsp;Zhi-Jun Zhang ,&nbsp;Rong-Tao Li","doi":"10.1016/j.jep.2026.121332","DOIUrl":"10.1016/j.jep.2026.121332","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shegan Mahuang Decoction (SMD), a traditional Chinese medicinal prescription outlined in “<em>Jin Gui Yao Lue</em>”. For approximately two thousand years, it has been widely used to treat asthma and flu-like symptoms in China and Japan for around twenty centuries. While the efficacy is confirmed, its pharmacological mechanism remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to systematically evaluate the protective effects of SMD against influenza A virus (IAV)-induced pneumonia and explore its action mechanism.</div></div><div><h3>Materials and methods</h3><div>Material basis and absorbed components of SMD were analyzed using UHPLC-HRMS. Integrating absorbed components and network pharmacology to predict its potential for treating influenza and its mechanism of action. By using the IAV pneumonia model, the abilities of SMD to suppress pathogenic-evil and pneumonia were confirmed using MDCK cells and BALB/c mice.</div></div><div><h3>Results</h3><div>UHPLC-HRMS identified 497 components in SMD, of which 125 were absorbed into the bloodstream of mice. Network pharmacology analysis based on absorbed components indicates SMD's anti-influenza effects through multiple biological processes associated with infection and immunity. SMD can inhibit viral proliferation <em>in vitro</em> and protect MDCK cells. It increased survival in infected mice from 8 to over 12 days. In the mice with IAV pneumonia, SMD significantly alleviated pathological damage, reduced viral proteins and mucins in lung tissue. It also regulates cytokines including TNF-α, IL-1β, and IL-6, and inhibited the activation of TLR/TAK/NF-κB and MEK/ERK signaling pathways.</div></div><div><h3>Conclusion</h3><div>This study has confirmed that SMD can alleviate the hyper-inflammatory response in the host induced by IAV. It suggests that SMD can treat pneumonia by inhibiting pathogenic-evil factors.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121332"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131903","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":"Pharmacological potential of chalepensin from Ruta chalepensis L.: Acute toxicity and in vivo antitumor activity in the L5178Y-R murine model","authors":"Nancy E. Rodríguez-Garza ,&nbsp;Ramiro Quintanilla-Licea ,&nbsp;Diana E. Caballero-Hernández ,&nbsp;Ana L. Delgado-Miranda ,&nbsp;César I. Romo-Sáenz ,&nbsp;Ricardo Gomez-Flores","doi":"10.1016/j.jep.2026.121334","DOIUrl":"10.1016/j.jep.2026.121334","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ruta chalepensis</em> L. (rue) is a medicinal plant commonly used in folk medicine and is known to contain bioactive secondary metabolites with pharmacological potential. Among these, chalepensin has been previously described to exhibit antitumor activity <em>in vitro</em>; however, its <em>in vivo</em> efficacy and safety profile remain poorly characterized.</div></div><div><h3>Aim of the study</h3><div>To evaluate the <em>in vitro</em> and <em>in vivo</em> antitumor activity of chalepensin against L5178Y-R murine lymphoma and to assess its acute toxicity profile.</div></div><div><h3>Materials and methods</h3><div>Chalepensin was isolated from the leaves and stems of <em>R. chalepensis</em>. Cytotoxic activity was determined <em>in vitro</em> with the MTT assay against tumor and normal cell lines. <em>In silico</em> analyses were performed to predict pharmacokinetic properties and explore potential molecular interactions. Acute toxicity was assessed in BALB/c mice following intraperitoneal administration of chalepensin (100 and 1000 mg/kg). Antitumor efficacy was evaluated in BALB/c mice bearing L5178Y-R lymphoma by monitoring tumor volume and survival.</div></div><div><h3>Results</h3><div>Chalepensin exhibited potent cytotoxic activity against L5178Y-R cells (IC₅₀ = 8.1 μg/mL; SI = 66.5). <em>In silico</em> analyses predicted favorable pharmacokinetic properties. Acute toxicity studies revealed no mortality, clinical signs of toxicity, or significant alterations in biochemical and hematological parameters. <em>In vivo</em>, chalepensin induced a significant reduction in tumor volume between days 10 and 20 (p &lt; 0.05) and significantly prolonged mean survival time, showing comparable or superior efficacy to vincristine under the tested conditions. Molecular docking suggested a preferential interaction with the Cyclin A2–CDK2 complex, supporting a potential cytostatic mechanism consistent with the observed <em>in vivo</em> effects.</div></div><div><h3>Conclusion</h3><div>Chalepensin demonstrates promising antitumor activity against L5178Y-R murine lymphoma, along with a favorable acute toxicity profile. These findings support its potential for further preclinical development and warrant additional studies to elucidate its molecular mechanisms and long-term safety.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121334"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137524","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":"Integrating transcriptomics and metabolomics to explore the therapeutic effects and mechanisms of Zhushagen-Shandougen herb pair on chronic pharyngitis","authors":"Yun Chen ,&nbsp;Hui Shi ,&nbsp;Zhou-Jie Yang ,&nbsp;Xiong-wei Liu ,&nbsp;Li-Yan zhang ,&nbsp;Xiu Dong ,&nbsp;Xing-Yan Ma ,&nbsp;Ying Zhou ,&nbsp;Ting-Ting Feng","doi":"10.1016/j.jep.2026.121291","DOIUrl":"10.1016/j.jep.2026.121291","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ardisia crenata</em> Sims (Zhushagen) and <em>Sophora tonkinensis</em> Gagnep. (Shandougen), core components of Kaihoujian Spray, are used in Miao medicine to treat chronic pharyngitis (CP), but their mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the therapeutic effects of Zhushagen, Shandougen, and their combination (Zhushagen-Shandougen) on CP, and to elucidate the pharmacological mechanisms via serum metabolomics and pharyngeal mucosa transcriptomics.</div></div><div><h3>Methods</h3><div>A rat model of chronic pharyngitis was induced by ammonium hydroxide administration. Therapeutic effects were evaluated via behavioral assessment, histopathological examination, and ELISA for inflammatory cytokines. For mechanism exploration, transcriptomic analysis of pharyngeal mucosa and metabolomic analysis of serum were performed in rats. Correlation analysis was used to integrate transcriptomic and metabolomic data, and a core regulatory network was constructed based on key genes, metabolites, and pathways. Potential targets were validated by immunohistochemistry and RT-qPCR.</div></div><div><h3>Results</h3><div>All treatments dose-dependently ameliorated CP symptoms, reduced the pro-inflammatory cytokines IL-1β, IL-6, PGE2, and TNF-α, increased IL-10, and alleviated mucosal lesions, with the combination being the most potent. In omics analyses, 32 differential metabolites and 121 differential mRNAs were identified. KEGG enrichment showed that differential metabolites were primarily involved in riboflavin and glutathione metabolism, while differential mRNAs were enriched in the MAPK and PI3K-Akt signaling pathways. RT-qPCR validation of 9 genes confirmed the transcriptomic results; notably, the mRNA expressions of <em>p38</em>, <em>erk1/2</em>, <em>pi3k</em>, and <em>akt</em> were altered. Immunohistochemistry further confirmed changes in the protein levels of p38, ERK1/2, and Akt, as well as the activations of p38 and PI3K, validating the omics findings.</div></div><div><h3>Conclusion</h3><div>Zhushagen, Shandougen, and Zhushagen-Shandougen exert therapeutic effects on CP. The present study found that Zhushagen-Shandougen may suppress the PI3K/Akt and MAPK signaling pathways, thus alleviating ammonium hydroxide-induced CP. The elucidated mechanism provides a significant theoretical foundation and a novel therapeutic approach for the treatment of CP.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121291"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137569","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":"2026-02-04","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":"Luteolin, a bioactive compound from Celastrus orbiculatus stem, inhibits cervical cancer via CA2 suppression: A translational study bridging basic research and clinical application","authors":"Jue Chen ,&nbsp;MengKe Wu ,&nbsp;RongRong Zhang ,&nbsp;Yun Cao ,&nbsp;Xiangyan Chen ,&nbsp;Xinyu Liu ,&nbsp;Yanqing Liu ,&nbsp;Wei Jiang ,&nbsp;Qiang Wang","doi":"10.1016/j.jep.2026.121326","DOIUrl":"10.1016/j.jep.2026.121326","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Celastrus orbiculatus&lt;/em&gt; Thunb. is a traditional herb with the effects of eliminating wind and dampness, activating blood circulation and detoxifying.It is commonly used in the treatment of malignant tumors and rheumatoid arthritis in China. Previous basic research has confirmed its significant anti-tumor activity. However, the underlying mechanism of its treatment in cervical cancer has not been reported.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;Building on findings from a retrospective clinical analysis, this study applied bioinformatics and experimental validation to elucidate the mechanism by which luteolin, a major constituent of &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem, and its target protein Carbonic Anhydrase II (CA2) exert inhibitory effects on cervical cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A retrospective clinical analysis was first conducted to assess the impact of &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem (30 g/day) combined with postoperative concurrent chemoradiotherapy (weekly cisplatin) on recurrence in cervical cancer patients. Liquid chromatography–mass spectrometry (LC–MS) was then used to identify the principal active components of &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem. Public databases were employed to determine the core targets of these active components against cervical cancer. Prognostic analysis was performed using data from The Cancer Genome Atlas (TCGA). Expression of core target proteins was validated in clinical surgical specimens of cervical cancer. Finally, the inhibitory effects of the identified active compound (luteolin) acting through the target protein (CA2) were confirmed using lactate dehydrogenase (LDH) release assays, gene expression modulation, and a murine xenograft tumor model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Retrospective clinical analysis demonstrated that &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem (30 g/day) combined with weekly cisplatin concurrent radiotherapy significantly prolonged postoperative disease-free survival in cervical cancer patients. In vitro, the extract of &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem suppressed cervical cancer cell proliferation. Luteolin was identified as a major constituent of the extract. Further analysis revealed that CA2 was characteristically overexpressed in epithelial tumor cells of cervical cancer tissues, but not in stromal cells, and served as a core target of luteolin. Modulation of CA2 expression or luteolin-mediated intervention effectively inhibited cervical cancer cell proliferation and invasion, promoted apoptosis in vitro, and suppressed the growth of xenograft tumors in vivo.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Luteolin is the primary bioactive constituent of &lt;em&gt;Celastrus orbiculatus&lt;/em&gt; stem responsible for its inhibitory effects on cervical cancer. CA2, characteristically overexpressed in epithelial-derived cervical cancer cells, plays a pivotal role in promoting cancer cell proliferation and invas","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121326"},"PeriodicalIF":5.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131901","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}