Journal of ethnopharmacology最新文献

{"title":"Neuroprotective effect of the herbal pair Coptidis Rhizoma-Cinnamomi Cortex against 6-OHDA-induced Parkinson's disease rats through promotion of autophagy via the PI3K/AKT/mTOR pathway","authors":"Yimeng Zhao ,&nbsp;Yuqing Ma ,&nbsp;Lijuan Xiong ,&nbsp;Jiaxuan Ai ,&nbsp;Xing Wang ,&nbsp;Xiaoqing Chen ,&nbsp;Yaonan Wang ,&nbsp;Yinying Ba ,&nbsp;Xia Wu","doi":"10.1016/j.jep.2025.120582","DOIUrl":"10.1016/j.jep.2025.120582","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Parkinson's disease (PD) is a common neurodegenerative disorder with a universal and fast-growing increase in both prevalence and incidence worldwide. Coptidis Rhizoma-Cinnamomi Cortex (CR-CC), a classic herbal pair comprising the Jiaotai Pill, has been widely used in clinical practice to improve PD and its associated symptoms including anxiety and insomnia. However, the mechanism of the action of CR-CC in improving PD remains to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>To investigate the therapeutic effect of CR-CC against PD rats and the relevant mechanism.</div></div><div><h3>Materials and methods</h3><div>A rat model of PD was established through unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. The therapeutic effects were evaluated by three kinds of behavioral tests, the levels of oxidative stress markers, and tyrosine hydroxylase (TH). The neurotransmitters and their metabolites were determined by UPLC-MS/MS. Immunohistochemistry, immunofluorescence, and western blotting were conducted to detect the TH expression and α-Synuclein (α-Syn) level in the substantia nigra (SN). The potential targets and related signaling pathways were analyzed and predicted using network pharmacology analysis and molecular docking, and the expression of LC3II/LC3I, p62, and the proteins related to PI3K/AKT/mTOR pathways in the SN of PD rats was assessed by western blotting.</div></div><div><h3>Results</h3><div>CR-CC ameliorated motor dysfunction and oxidative damage in the serum of PD rats and modulated the neurotransmitter levels of the striatum on the injured side. It also attenuated the dopaminergic neuronal loss and abnormal aggregation of α-Syn in the SN, showing similar effects compared with CR and CC administration alone. Network pharmacology and molecular docking analysis suggested that MTOR, PIK3CA, and MAPK3 related to autophagy would be the core targets for the active compounds of CR-CC. Further studies showed that CR-CC increased the LC3II/LC3I ratio, decreased the p62 level, and regulated the expression of proteins related to the PI3K/AKT/mTOR pathway in PD rats.</div></div><div><h3>Conclusion</h3><div>The results showed that CR-CC exerted neuroprotective effects by regulating autophagy through the PI3K/AKT/mTOR pathway to reduce the α-Syn level in the SN of PD rats and showed similar effects to those of CR and CC alone.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120582"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069737","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 Mume Fructus extract on smoking-induced cough and TNBS-induced colitis in rats and its underlying mechanisms based on gut-lung body fluid metabolism","authors":"Zhengxu Zhang,&nbsp;Lishan Ouyang,&nbsp;An Sun,&nbsp;Zongjin Pu,&nbsp;Yixin Liu,&nbsp;Ying Peng,&nbsp;Xiaobo Li","doi":"10.1016/j.jep.2025.120539","DOIUrl":"10.1016/j.jep.2025.120539","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Mume Fructus (MF) has been widely used in traditional Chinese medicine to alleviate chronic cough, diarrhea, and dysentery. Our previous studies confirmed that MF exerts beneficial effects on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. However, the active components of MF and underlying mechanisms by which it alleviates both cough and colitis remain incompletely understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to further elucidate the active components of MF and underlying mechanisms for alleviating both cough and colitis.</div></div><div><h3>Materials and methods</h3><div>UPLC-Q-TOF-MS/MS was used to analyze the chemical profiles of MF ethanol extract and its fractions (MFE0, MFE40, and MFE100). A rat model was established through simultaneous cigarette smoke exposure and TNBS enema administration to evaluate the ameliorative effects of these fractions on both cough and colitis. Molecular docking was combined with western blotting to investigate the underlying mechanisms.</div></div><div><h3>Results</h3><div>Among the three fractions of MF, MFE40 and MFE100 significantly reduced cough frequency and pulmonary edema, ameliorated colon shortening, and alleviated pathological damage in the lungs and colon of model rats. In contrast, MFE0 showed limited efficacy against cough and pulmonary edema. UPLC-Q-TOF-MS/MS identified key compounds in MFE40 and MFE100—including citric acid derivatives, hydroxycinnamic acid derivatives, flavonoids, unsaturated fatty acids, and terpenoids—which exhibited strong binding affinity to TLR4, AQP5, αENaC, TRPV1, and Na⁺/K⁺-ATPase in molecular docking analysis. Western blotting confirmed that MFE40 and MFE100 modulated expression of αENaC, TLR4, AQP5, and AQP3 in lung and colon tissues, suggesting these fractions improve cough and colitis by regulating body fluid metabolism and reducing inflammation.</div></div><div><h3>Conclusion</h3><div>MFE40 (primarily citric acid and hydroxycinnamic acid derivatives) and MFE100 (mainly flavonoids, unsaturated fatty acids, and terpenoids) alleviated smoking-induced cough and TNBS-induced colitis in rats. These effects are mediated through TLR4 regulation and the activation of AQPs and ENaC, which together regulate body fluid metabolism and mitigate inflammatory injury in the lungs and intestines. This study elucidates the active components and underlying mechanisms of MF in mitigating cough and colitis, providing scientific evidence for the clinical application of MF in managing IBD and its extraintestinal manifestations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120539"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069748","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":"Activity-guided isolation of sesquiterpene coumarins from Ferula assa-foetida as monoamine oxidase inhibitors: Investigation on their therapeutic implications in a mice model of Parkinson's disease","authors":"Chayan Banerjee ,&nbsp;Priyanka Yatham ,&nbsp;Suchismita Mukherjee ,&nbsp;Joy Chakraborty ,&nbsp;Deepak Kumar","doi":"10.1016/j.jep.2025.120608","DOIUrl":"10.1016/j.jep.2025.120608","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ferula assa-foetida</em><em>,</em> has been used for centuries as a spice, is well acknowledged as a traditional medicine in Ayurveda, and as a folklore medicine across the globe for its neurological benefits. In recent years, modern pharmacological studies have augmented its potential against various neurological disorders, thus signifying its therapeutic importance against neurological disorders in both ethnic and modern medicinal aspects.</div><div><strong><em>Aim of the study:</em></strong> We aimed to identify Monoamine oxidase (MAO)-inhibiting sesquiterpene coumarins from <em>Ferula assa-foetida</em> through activity-guided isolation and evaluate them using <em>in vitro</em> and <em>in vivo</em> models relevant to Parkinson's disease (PD).</div></div><div><h3>Materials and methods</h3><div>LC-MS² was used for the detection of the sesquiterpene coumarins, followed by chromatographic fractionation, and semi-preparative HPLC-mediated purification of the 19 compounds; their structures were established by the combined use of MS, 1D, and 2D NMR techniques. MAO assay identified two active compounds for further study. Toxicity was evaluated in SH-SY5Y cells, Drosophila, and C57BL/6 mice. Effects on mice brain MAO activity and striatal dopamine were examined by LC-MS/HPLC. Finally, neuroprotective effects were validated in an MPTP-induced PD mouse model.</div></div><div><h3>Results</h3><div>LC-MS² analysis confirmed the presence of naturally occurring sesquiterpene coumarin hybrids with significant structural diversity in <em>Ferula assa-foetida</em> oleo-gum-resin, and 19 compounds were isolated for characterization. After preliminary <em>in vitro</em> MAO assays karatavicinol and farnesiferol C were selected for further evaluation. Both compounds exhibited BBB permeability, inhibited MAO activity in mice brain, and effectively elevated dopamine levels in the striatum. Additionally, these compounds demonstrated their therapeutic potential against PD in a mice model.</div></div><div><h3>Conclusions</h3><div>The 7 substituted coumarins with the structurally diverse sesquiterpene moieties displayed varying degrees of MAO inhibition. Further detailed investigation on karatavicinol and farnesiferol C confirmed that both compounds holds significant therapeutic potential to address PD related dopamine deficiency, motor incoordination, and neurodegeneration.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120608"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069729","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 anti-triple-negative breast cancer mechanisms and mitigating toxicity of Fritillaria thunbergii Miq.: A multi-omics and network pharmacology approach","authors":"Yubin Zhu ,&nbsp;Yuqing Zhang ,&nbsp;Xinni Li ,&nbsp;Luyao Zhang ,&nbsp;Zhixin Shen","doi":"10.1016/j.jep.2025.120600","DOIUrl":"10.1016/j.jep.2025.120600","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Fritillaria thunbergii</em> Miq. (Zhebeimu, ZBM) is traditionally recognized in Chinese medicine for its effects of clearing heat, resolving phlegm, suppressing cough, detoxifying, dissipating nodules, and resolving abscesses—properties that align closely with the pathogenesis of breast cancer. Classical texts including <em>Shennong Bencao Jing</em> and <em>Bencao Zheng</em> document its historical use in breast cancer treatment.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate the potential therapeutic mechanisms and safety profile of the traditional Chinese medicine ZBM against triple-negative breast cancer (TNBC) using in silico methodologies.</div></div><div><h3>Materials and methods</h3><div>This computational study integrated network pharmacology, machine learning, and single-cell RNA sequencing to systematically identify ZBM's bioactive components and potential targets against TNBC. Molecular docking and dynamics simulations were employed to characterize interactions between key compounds and targets, while network toxicology assessed potential toxicity risks.</div></div><div><h3>Results</h3><div>Our multi-omics approach identified 42 bioactive ZBM components and 148 potential TNBC targets. Among these, machine learning algorithms prioritized five key autophagy-related genes, with CXCR4 selected as the core autophagy-associated target for computational validation. Molecular simulations predicted strong binding between hapepunine and CXCR4. Meanwhile, subtype analysis at the single-cell level revealed that BL TNBC subtypes may be particularly sensitive to ZBM compounds. Network toxicology revealed potential hepatotoxicity/nephrotoxicity risks. These risks were computationally mitigated through structural optimization of hapepunine derivatives.</div></div><div><h3>Conclusions</h3><div>This study not only provides a novel mechanistic framework for ZBM's anti-TNBC activity but also demonstrates the utility of network toxicology coupled with structural optimization in proactively identifying and mitigating potential toxicity liabilities of natural product derivatives.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120600"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069723","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":"Non-targeted metabolomic and chemometric analysis of Gardeniae Fructus (Zhizi): Linking processing to chemical and bioactive changes","authors":"Ling Liang ,&nbsp;Jisheng Liu ,&nbsp;Jiangyi Luo,&nbsp;Yasi Deng,&nbsp;Shiqi Liu,&nbsp;Qingling Xie,&nbsp;Mengyun Wang,&nbsp;Tingsi Guo,&nbsp;Xingwang Leng,&nbsp;Pingan Liu,&nbsp;Wei Wang,&nbsp;Hanwen Yuan","doi":"10.1016/j.jep.2025.120606","DOIUrl":"10.1016/j.jep.2025.120606","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Gardeniae Fructus (Zhizi, ZZ), the fruit of <em>Gardenia jasminoides</em> Ellis, exhibits anti-inflammatory and hepatoprotective effects, etc. Processing alters its properties, enhances therapeutic effects, and reduces toxicity. Furthermore, The chemical composition of ZZ seed and pericarp is significantly different. Studying the alterations in chemical components of the seed and pericarp under various processing conditions and the resulting variances in biological activities is highly valuable.</div><div>Aim of the study: This study aimed to investigate the changes in the chemical composition and biological activity of ZZ during processing.</div></div><div><h3>Materials and methods</h3><div>This study employed high-performance liquid chromatography-diode array detection (HPLC-DAD) and liquid chromatography coupled to electrostatic orbitrap high-resolution mass spectrometry (LC-Orbitrap-MS), along with chemometric analysis and non-targeted metabolomics, to investigate variances in components of ZZ seed and pericarp and their transformations during processing. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were utilized to evaluate the anti-inflammatory effects of ZZ by measuring nitric oxide (NO) production with the Griess reagent method. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6) were determined using ELISA technique. Acetaminophen (APAP)-induced HepG2 cells were used to investigate the hepatoprotective of ZZ.</div></div><div><h3>Results</h3><div>Using non-targeted metabolomics and chemometrics, the study identified 353 differential features between the ZZ raw seed (RS) and the raw pericarp (RP). During processing, 382 and 386 significant features were found in seed and pericarp, respectively. A total of 210 compounds were identified by reference standards, fragmentation pattern, molecular networking, mzCloud, mzVault, in-house database, and a predictive database. Furthermore, bioassay tests showed reduced anti-inflammatory and hepatoprotective effects during processing. Geniposide and <em>trans</em>-crocin I were identified as primary anti-inflammatory and hepatoprotective compounds.</div></div><div><h3>Conclusion</h3><div>The chemical difference between the pericarp and seed of ZZ is obvious, and the chemical changes during processing have a significant impact on the activities. Proper processing is crucial for maximizing the therapeutic effects of ZZ.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120606"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069751","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":"Therapeutic effects of G90′-ES2 protein complex from regenerated Eisenia fetida on radiation-induced skin injury","authors":"Yuwei Yang ,&nbsp;Peng Ni ,&nbsp;Lixue Ma ,&nbsp;Haikang Tang ,&nbsp;Jiaming Yang ,&nbsp;Xiaoliang Zhou ,&nbsp;Yikun Sun ,&nbsp;Wenqing Xu","doi":"10.1016/j.jep.2025.120583","DOIUrl":"10.1016/j.jep.2025.120583","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Radiation-Induced Skin Injury (RISI) is the major cutaneous side effect met by cancer patients who received radiotherapy. Disposed earthworm (Dilong) has been historically employed for treating various ailments in ancient China. Amputated-regeneration and high radiation-tolerant are two distinctive characteristics for earthworms. These features might due to their abundant biologically active substances (65 % composed of proteins), which make them attractive candidates for radioprotector development.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate therapeutic mechanism of regenerated <em>E. fetida</em> protein extract (G90′-ES2) in mitigating RISI, and reveal therapeutic potential macromolecules by proteomic analysis.</div></div><div><h3>Materials and methods</h3><div>Protein salt precipitation method was firstly adopted to obtain G90′-ES2/G90-ES2 protein complex. Their radioprotective activities were evaluated <em>in vitro</em> by cell viability, migration, ROS accumulation, EdU proliferation, cell cycle and apoptosis assays. A combined radiogenic injury mice model was constructed to analyze radiotherapeutic function of G90′-ES2 <em>in vivo</em>. Its mechanism against RISI was illustrated by RNA-Seq analysis, qPCR, and HIF Luciferase Reporter Assay. Finally, a nanoElute UPLC-MS/MS method was used to elucidate therapeutic potential macromolecules in G90′-ES2.</div></div><div><h3>Results</h3><div>We discovered that G90′-ES2 displayed higher efficacy than G90-ES2 in mitigating RISI, mainly by activating radio-resistant HIF-1 pathway, redistributing cell cycle phases (S-phase preservation), accelerating re-epithelialization, and enhancing tissue angiogenesis. The significantly up-regulated proteins (including lumbrokinase, aquaporin, RAD51C, TCTP, and SCBP2) in G90′-ES2 might hold particular importance for its therapeutic effect against RISI.</div></div><div><h3>Conclusions</h3><div>This investigation will broaden our understanding of the radiation-tolerant and regenerative capacities for earthworm; also provide medical candidates for the development of skin-specific radioprotector.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120583"},"PeriodicalIF":5.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069693","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":"Typhae pollen attenuates atherosclerosis by enhancing vascular endothelium function and lipid metabolism","authors":"Yu-Jia Kuang ,&nbsp;Qian-Qian Chen ,&nbsp;Jin-hua Hao ,&nbsp;Yang Lin ,&nbsp;Ping-Ting Xiao ,&nbsp;E-Hu Liu","doi":"10.1016/j.jep.2025.120604","DOIUrl":"10.1016/j.jep.2025.120604","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Atherosclerosis is a pathological condition characterized by the accumulation of lipid-rich lesions within the endothelial layer, and it remains a significant contributor to global morbidity and mortality. Typhae Pollen (TP) has been extensively used in the treatment of blood stasis. However, the potential protective effects and underlying mechanisms of TP in atherosclerosis remain poorly understood.</div></div><div><h3>Aim of the study</h3><div>To explore the protective effects and mechanisms of Typhae Pollen extract (TPEX) on atherosclerosis.</div></div><div><h3>Materials and methods</h3><div>We established atherosclerosis models in ApoE^−/− mice using high-fat diet (HFD), with continuous oral administration of TPEX at specified doses and intervals <em>in vivo</em>. To explore the underlying mechanisms of TPEX, we employed integrated network pharmacology and transcriptome analysis. <em>In vitro</em>, palmitic acid and H₂O₂ induced primary hepatic cells lipid accumulation and endothelial cells dysfunction model were employed to investigate the potential mechanisms of TPEX using Western blot, immunofluorescence, nuclear/cytoplasmic proteins isolation techniques.</div></div><div><h3>Results</h3><div>TPEX improved aortic lipid deposition and arterial injury, alleviated hyperlipidemia, and reduced liver damage in HFD-induced ApoE^−/− mice. Mechanistically, TPEX mitigated endothelial cell senescence through the p53/p21 signaling pathway, suppressed inflammation by inhibiting the translocation of p65 into the nucleus, and alleviated oxidative stress by preventing the nuclear translocation of NRF2 and modulating the NRF2/HO-1 pathway. Furthermore, TPEX reduced inflammation and regulated lipid metabolism via the NOD signaling pathway and the SREBPs signaling pathway in the liver.</div></div><div><h3>Conclusion</h3><div>TPEX alleviates atherosclerosis by regulating endothelial dysfunction, hepatic lipid metabolism, and inflammatory processes. These findings provide new insights into the protective role of TPEX in atherosclerosis, especially regarding endothelial dysfunction and hepatic lipid metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120604"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064816","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":"Bu Zhong Yi Qi Tang targets key monocyte-associated genes to enhance sepsis therapy","authors":"Yuanyuan Zhou ,&nbsp;Wenwen Sun ,&nbsp;Jing Zhou ,&nbsp;Pei Yang ,&nbsp;Jinqiu Wang ,&nbsp;Biao Xu ,&nbsp;Jiwei Hou ,&nbsp;Kaiyong Yang","doi":"10.1016/j.jep.2025.120610","DOIUrl":"10.1016/j.jep.2025.120610","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Sepsis is a life-threatening condition resulting from an uncontrolled immune response to infection, leading to organ dysfunction and severe complications. <em>Bu Zhong Yi Qi Tang (BZYQT)</em>, a traditional Chinese medicinal formulation, has been recognized for its diverse pharmacological effects, particularly in modulating immune responses and alleviating inflammation. However, the specific role and mechanism of <em>BZYQT</em> in the adjunctive treatment of sepsis are still unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate the role and underlying mechanisms of <em>BZYQT</em> in the adjunctive therapy of sepsis.</div></div><div><h3>Materials and methods</h3><div>scRNA-seq was employed to analyze PBMCs from patients with sepsis and healthy controls, identifying cell populations and functional states. Pseudotime and cell-cell communication analyses were conducted to investigate the origins and interactions of Sep_monocytes. hdWGCNA and machine learning techniques were utilized to identify key genes. The adjuvant therapeutic efficacy of <em>BZYQT</em> was assessed in a cecal ligation and puncture (CLP) mouse model, as well as in clinical trials.</div></div><div><h3>Results</h3><div>Seven populations of PBMCs and twelve subclusters of monocytes were identified, with two subclusters (Sep_monocytes) enriched in sepsis patients. Furthermore, critical gene modules were identified, with METTL9, SAT1, and SRGN being pinpointed as potential sepsis biomarkers. Notably, <em>BZYQT</em> was found to target these genes, modulating their expression. In the CLP mouse model, BZYQT administration (0.2 ml/10 g/d) in combination with imipenem/cilastatin (50 mg/kg/d) led to improved survival rates, significantly reduced bacterial loads, diminished inflammation, and enhanced antibacterial effects. Clinically, <em>BZYQT</em> alleviated symptoms, modulated immune cells, and reduced inflammatory markers, underscoring its potential efficacy as an adjunctive therapy for sepsis.</div></div><div><h3>Conclusion</h3><div><em>BZYQT</em> enhances sepsis therapy by targeting critical monocyte-associated genes, thereby modulating immune responses and reducing inflammation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120610"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064703","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":"Macelignan, a lignan from Myristica fragrans Houtt., rescues mitochondrial homeostasis and prevents cognitive decline in vascular dementia by modulating the mTOR-Mitophagy axis","authors":"Zhengyu Qi ,&nbsp;Xinge Chu ,&nbsp;Sha Li ,&nbsp;Qiaoyun Bai ,&nbsp;Ningpo Ding ,&nbsp;Guanghai Yan ,&nbsp;Hailing Yu ,&nbsp;Chunai Cui","doi":"10.1016/j.jep.2025.120603","DOIUrl":"10.1016/j.jep.2025.120603","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Myristica fragrans Houtt. has a long history of use in traditional medicine as a nervine tonic for enhancing cognitive function, relieving anxiety, and managing neurological symptoms associated with aging. Given its established ethnopharmacological profile, we postulated that its principal active lignan, Macelignan, could exert potent neuroprotective effects in the context of neurodegenerative diseases like vascular dementia (VaD).</div></div><div><h3>Aim of the study</h3><div>This study was designed to investigate the neuroprotective properties of Macelignan in a preclinical model of vascular dementia (VaD) and to elucidate the underlying molecular mechanisms, with a particular focus on its modulation of the mTOR signaling pathway and mitochondrial homeostasis.</div></div><div><h3>Materials and methods</h3><div>In this study, <em>in vivo</em> and <em>in vitro</em> models of ischemia-hypoxia were established in Wistar rats by bilateral common carotid artery occlusion (BCCAo) and in HT22 neuronal cells with cobalt chloride (CoCl₂) treatment, respectively. The resulting cognitive, pathological, and cell survival damages were comprehensively assessed using a battery of behavioral tests, histological staining (H&amp;E and Nissl), and the CCK-8 assay. To elucidate the underlying mechanisms, we first predicted and validated the direct interaction between the drug and its core target protein using transcriptome sequencing (RNA-seq) combined with molecular docking and dynamics simulations. Subsequently, changes in key signaling pathways, including mTOR, mitochondrial dynamics, autophagy, and apoptosis, were systematically investigated utilizing Seahorse metabolic flux analysis, transmission electron microscopy (TEM), various fluorescent probes (JC-1, MitoSOX, ROS, Ca²⁺), Western blotting, and immunofluorescence (IF). All data were statistically analyzed using GraphPad Prism 10.1.2.</div></div><div><h3>Results</h3><div>In vivo, we demonstrate that Macelignan ameliorates neuronal damage and cognitive deficits in a model of vascular dementia by directly targeting and activating the mTOR signaling pathway. At the cellular level, this mTOR activation orchestrates a multifaceted protective response, which includes restoring mitochondrial function and homeostasis, enhancing antioxidant defenses, suppressing the stress-induced expression of mitophagy-related proteins Beclin-1 and Parkin, and potently inhibiting apoptosis. Critically, these neuroprotective effects of Mace were completely abrogated by the mTORC1-specific inhibitor rapamycin, definitively establishing that its therapeutic efficacy is dependent on mTOR activation.</div></div><div><h3>Conclusions</h3><div>Macelignan targets and activates mTOR to restore mitochondrial homeostasis, thereby ameliorating vascular dementia.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120603"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061011","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":"Zhenqi Buxu oral liquid ameliorates inflammaging and aging associated dysfunction via downregulation of TNF-ɑ-mediated inflammatory pathways in mice","authors":"Xinqing Jiang ,&nbsp;Weidong Ye ,&nbsp;Zhengkai Wang ,&nbsp;Keying Zhu ,&nbsp;Jun Ping ,&nbsp;Liujun Xu ,&nbsp;Beier Jiang ,&nbsp;Shengmei Zhu ,&nbsp;Maoxiang Qian ,&nbsp;Lifeng Xu ,&nbsp;Feng Zhang ,&nbsp;Sijia Chen","doi":"10.1016/j.jep.2025.120611","DOIUrl":"10.1016/j.jep.2025.120611","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Aging is associated with a persistent, low-grade inflammatory state termed “inflammaging”, driven by the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP). Zhenqi Buxu Oral Liquid (ZQBX) is a widely used traditional Chinese medicine formula known to treat human weakness and have potential anti-aging effects.</div></div><div><h3>Aim of study</h3><div>To explore the geroprotective effects of ZQBX and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We used a natural aging mouse model to evaluate the effects of ZQBX intervention on aging. Tissue staining, serum ELISA assays, physical function analysis, network pharmacological analysis and molecular docking analysis were employed to describe the phenotypic and mechanistic effects of ZQBX.</div></div><div><h3>Results</h3><div>ZQBX treatment protected against age-related declines in liver function and hepatic steatosis, mitigated chronic inflammation, and improved insulin sensitivity and glucose metabolism in aged mice. Mechanically, ZQBX reduced SASP in senescent hepatic cells to delay liver aging through inhibiting the TNF-α signaling pathway.</div></div><div><h3>Conclusion</h3><div>The pharmacological significance of ZQBX in modulating senescence-associated phenotypes implies its potential benefits in regulating the activities of senescent cells, suggesting possible contributions to future geriatric medicine.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120611"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064837","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}