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Ferulic acid in Chaihu Shugan San modulates depression-like behavior, endothelial and gastrointestinal dysfunction in rats via the Ghrl-Edn1/Mecp2/P-mTOR/VEGFA pathway: A multi-omics study
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-22 DOI: 10.1016/j.jep.2025.119624
Min Xu , Qian-tao Zhang , Li Zhou , Ya-wen Cai , Hao Liu , Qiu-long Zhao , Jing-hua Tian , Yun-ke Huang , Ping Ren , Xi Huang
{"title":"Ferulic acid in Chaihu Shugan San modulates depression-like behavior, endothelial and gastrointestinal dysfunction in rats via the Ghrl-Edn1/Mecp2/P-mTOR/VEGFA pathway: A multi-omics study","authors":"Min Xu , Qian-tao Zhang , Li Zhou , Ya-wen Cai , Hao Liu , Qiu-long Zhao , Jing-hua Tian , Yun-ke Huang , Ping Ren , Xi Huang","doi":"10.1016/j.jep.2025.119624","DOIUrl":"10.1016/j.jep.2025.119624","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In a global context of escalating multimorbidity, characterized by the co-occurrence of major depressive disorder (MDD), endothelial dysfunction (ED), and gastrointestinal dysregulation (GD), the quest for effective treatments has become paramount. Central to these interconnected conditions is oxidative stress (OS), a pivotal factor that has been extensively studied yet remains inadequately addressed. This study introduces Chaihu-Shugan-San (CSS) and its absorbed component ferulic acid (FA), a potent antioxidant derived from medicinal plants, as a novel therapeutic approach with the unique ability to counter the multifaceted effects of acute forced swimming (AFS)-induced depression, ED, and GD. Unlike traditional single-disease-focused studies, our research explores the synergistic effects of CSS and FA across these interrelated disorders, offering a groundbreaking perspective.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate CSS and FA in treating depression-related multimorbidity triggered by AFS and to uncover the shared underlying mechanisms of FA.</div></div><div><h3>Materials and methods</h3><div>A depression-like model in rats was induced by AFS, and an OS model was established in endothelial cells (ECs) through hydrogen peroxide treatment. We investigated the effects of CSS and FA on MDD, ED, and GD in rats and OS levels in ECs. Our assessments included hematoxylin and eosin (HE) staining, biochemical assays, and behavioral studies. We conducted an integrated analysis of transcriptomics, proteomics, and phosphoproteomics data to elucidate the underlying mechanisms. The identification of relevant targets was confirmed through Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), molecular docking studies, and an extensive literature review.</div></div><div><h3>Results</h3><div>Our findings indicate that CSS and FA not only significantly mitigate AFS-induced abnormalities in the open field test (OFT), forced swim test (FST), and related behaviors such as gastric emptying and intestinal transit in rats but also ameliorate depression, ED, GD, inflammation and OS-related biomarker levels, alongside HE staining in gastric sinus and aorta slices. The study also highlights that FA can influence OS and endothelial function in ECs. Moreover, a combined multi-omics analysis unveiled several OS-related pathways, including the mTOR and p53 signaling pathways. Our research elucidates that the Ghrl-Edn1/Mecp2/P-mTOR/Vegfa-associated OS signaling pathway is pivotal in countering AFS-induced multimorbidity, expanding beyond the conventional disease-specific focus.</div></div><div><h3>Conclusions</h3><div>This pioneering study underscores capability of CSS and FA to tackle AFS-induced multimorbidity concurrently and intricately details FA's antioxidative mechanisms within ECs. The insights gleaned offer a novel perspective on FA's role in multimorbidity r","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119624"},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700557","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}
引用次数: 0
Corrigendum to "Danggui niantong decoction attenuates synovial fibrosis through regulating PI3k/AKT signaling pathway" [J. Ethnopharmacol. 342 (2025) 119381].
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-22 DOI: 10.1016/j.jep.2025.119663
Qing Liao, Shuang Wu, Xiao Li, Li-Xia Yuan
{"title":"Corrigendum to \"Danggui niantong decoction attenuates synovial fibrosis through regulating PI3k/AKT signaling pathway\" [J. Ethnopharmacol. 342 (2025) 119381].","authors":"Qing Liao, Shuang Wu, Xiao Li, Li-Xia Yuan","doi":"10.1016/j.jep.2025.119663","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119663","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119663"},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692320","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}
引用次数: 0
Study on the effect of deer bone in improving rheumatoid arthritis based on the “drug-target-pathway” association network
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-22 DOI: 10.1016/j.jep.2025.119684
Yanlu Li , Aoyun Li , Yue Teng , Ting Ren , Junxia Ma , Weijia Chen , Jianming Li , Yan Zhao , Kun Shi , Ying Zong , Rui Du
{"title":"Study on the effect of deer bone in improving rheumatoid arthritis based on the “drug-target-pathway” association network","authors":"Yanlu Li , Aoyun Li , Yue Teng , Ting Ren , Junxia Ma , Weijia Chen , Jianming Li , Yan Zhao , Kun Shi , Ying Zong , Rui Du","doi":"10.1016/j.jep.2025.119684","DOIUrl":"10.1016/j.jep.2025.119684","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Deer bone is rich in proteins, free amino acids, chondroitin, organic calcium, phosphorus ions, and other active components. Deer bone had been used widely in antiquity and were first compiled in renowned ancient masterpiece ‘Mingyi Bielu (名医别录)’ written by Hongjing Tao. The deer bone is recorded as non-toxic and has the effects of replenishing bones, strengthening sinews, expelling wind-dampness from the body, promoting muscle growth, and healing wounds. Modern pharmacological research suggests that deer bone can help promote bone density and enhance bone strength, making it potentially valuable for the prevention and treatment of diseases such as rheumatoid arthritis and osteoporosis. However, current studies on the component analysis and pharmacological effects of deer bone against rheumatoid arthritis (RA) are incomplete, which to some extent hinders the development and clinical application of deer bone drugs.</div></div><div><h3>Aim of the study</h3><div>The components of deer bone were elucidated by label-free proteomics, and the drug-target-pathway association network was established by network pharmacology. The <em>in vitro</em> validation of the pathway provides a theoretical basis for deer bone as a potential therapeutic drug for rheumatoid arthritis, and also lays a solid foundation for the subsequent clinical application of the <em>in vitro</em> experiments established through serum pharmacology.</div></div><div><h3>Materials and methods</h3><div>We performed extraction of deer bone using traditional water extraction methods and employed label-free proteomics technology to identify and conduct bioinformatics analysis on the proteins and peptides in the deer bone hot water extract (DBHE). These components were considered potential drug targets, and we constructed a “drug-target-pathway” association network. Analysis revealed that the HIF-1 signaling pathway may be pivotal in DBWE's effect on RA. Hypoxia influences the occurrence and development of ferroptosis through various mechanisms. Therefore, we hypothesized that DBWE might induce ferroptosis, promoting apoptosis in RA-FLS under hypoxic conditions, thereby alleviating RA. Therefore, we performed flow cytometry, ELISA, immunofluorescence, RT-qPCR, and western blotting based on molecular docking. Considering the overall effect of drug metabolism post-ingestion, we used serum pharmacology to prepare serum for cellular administration.</div></div><div><h3>Results</h3><div>It showed that DBWE reduces inflammation and synovial proliferation by inhibiting HO-1, increasing ROS production, upregulating ACSL4 expression and inducing RA-FLS apoptosis in hypoxic conditions. This study reveals the potential mechanism by which DBWE modulates ferroptosis to attenuate synovial proliferation in a hypoxic microenvironment and improve RA.</div></div><div><h3>Conclusion</h3><div>These findings not only provide a theoretical basis for deer bone as a pote","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119684"},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700559","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}
引用次数: 0
Epimedii Folium and Ligustri Lucidi Fructus synergistically delay renal aging through AMPK/ULK1/Bcl2L13-mediated mitophagy
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119668
Yuting Long , Yuman Li , Zaina Ma , Yonghao Xie , Hui Zhao , Minyu Zhang , Renhui Liu
{"title":"Epimedii Folium and Ligustri Lucidi Fructus synergistically delay renal aging through AMPK/ULK1/Bcl2L13-mediated mitophagy","authors":"Yuting Long ,&nbsp;Yuman Li ,&nbsp;Zaina Ma ,&nbsp;Yonghao Xie ,&nbsp;Hui Zhao ,&nbsp;Minyu Zhang ,&nbsp;Renhui Liu","doi":"10.1016/j.jep.2025.119668","DOIUrl":"10.1016/j.jep.2025.119668","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The root of aging is attributed to kidney essence insufficiency and gradual loss of kidney function. The combination of <em>Epimedii Folium</em> and <em>Ligustri Lucidi Fructus</em> (ELL) is traditionally recognized to tonify kidney <em>yin</em> and <em>yang</em> and has significant efficacy in delaying aging and aging-related diseases, but little is known about the exact mechanism.</div></div><div><h3>Aim of the study</h3><div>The research focuses on the mechanism of delaying renal aging by which ELL regulates mitophagy through serine/threonine kinase AMP-activated protein kinase (AMPK)/UNC-51- like autophagy activating kinase 1 (ULK1)/B-cell lymphoma-2-like protein 13 (Bcl2L13) <em>in vivo</em>.</div></div><div><h3>Materials and methods</h3><div>We employed a rat model of natural aging, using rats of different ages as dynamic controls, and a natural aging mouse model to evaluate the effects of ELL on delaying renal aging via AMPK/ULK1/Bcl2L13. The assessment included renal histopathology, oxidative stress, cell senescence, mitochondrial dynamics, mitophagy, and the AMPK/ULK1/Bcl2L13 signaling pathway. In the aging rat model, network pharmacology and proteomics were combined to dissect the renal aging process, and a Multilayer Perceptron (MLP) -artificial neural networks (ANN) model was used to evaluate the effects of ELL comprehensively. In the aging mouse model, the AMPK inhibitor dorsomorphin was applied to assess whether the AMPK signaling pathway was involved in ELL-induced mitophagy.</div></div><div><h3>Results</h3><div>Compared with the young rats, the kidney exhibited signs of degenerative pathologies and increased oxidative stress in 17-month-old rats. A thorough analysis identified the mitochondrial protein Bcl2L13 as a crucial biomarker associated with renal aging. The AMPK/ULK1/Bcl2L13 pathway significantly regulated mitochondrial function and mitophagy, which were potential mechanisms underlying renal aging. In contrast to aged rats, the renal pathological changes and cell senescence in rats treated with ELL were significantly mitigated, the antioxidant capacity, mitochondrial dynamics, and mitophagy were improved, and the expression of AMPK/ULK1/Bcl2L13 was upregulated. After the application of AMPK inhibitor dorsomorphin, the effects of ELL were reversed. It appears that ELL modulates the AMPK/ULK1/Bcl2L13 signaling pathway, and upregulates mitophagy to potentially decelerate renal aging.</div></div><div><h3>Conclusions</h3><div>The findings indicate that aging kidneys display mitochondrial dysfunction, disorganization of mitochondria, and a decrease in mitophagy. Concurrently, ELL significantly regulates mitochondrial dynamics and mitophagy via AMPK/ULK1/Bcl2L13. This regulation helps mitigate mitochondrial dysfunction, suggesting ELL as a promising herbal remedy for delaying renal aging and age-related kidney diseases.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119668"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692335","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}
引用次数: 0
Scutellaria barbata ameliorates acute respiratory distress syndrome by inhibiting neutrophil-mediated inflammatory responses
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119653
Yu-Cheng Chen , Yao-Rong Lee , Yu-Chia Chang , Yi-Hsuan Wang , Shu-Yen Fang , Ching-Hsiung Lin , Po-Jen Chen , Tsong-Long Hwang
{"title":"Scutellaria barbata ameliorates acute respiratory distress syndrome by inhibiting neutrophil-mediated inflammatory responses","authors":"Yu-Cheng Chen ,&nbsp;Yao-Rong Lee ,&nbsp;Yu-Chia Chang ,&nbsp;Yi-Hsuan Wang ,&nbsp;Shu-Yen Fang ,&nbsp;Ching-Hsiung Lin ,&nbsp;Po-Jen Chen ,&nbsp;Tsong-Long Hwang","doi":"10.1016/j.jep.2025.119653","DOIUrl":"10.1016/j.jep.2025.119653","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The traditional medicinal herb <em>Scutellaria barbata</em> D. Don (commonly known as Ban Zhi Lian) is renowned for its heat-clearing and detoxifying properties and has been used to treat inflammatory conditions and various cancers. While lung inflammation is an indication for <em>S. barbata</em>, its effects on acute respiratory distress syndrome (ARDS) remain unclear.</div></div><div><h3>Aim of the study</h3><div>Dysregulated neutrophilic inflammation plays a critical role in the pathogenesis of ARDS. In this study, we aimed to investigate the novel application of <em>S. barbata</em> in treating neutrophilic inflammation and ARDS. We evaluated the therapeutic potential of the ethanol extract of <em>S. barbata</em> (SB-EtOH) in mitigating neutrophil-driven inflammatory responses.</div></div><div><h3>Materials and methods</h3><div>The chromatographic fingerprint of SB-EtOH was analyzed, and its ethnopharmacological mechanisms were examined for their effects on inflammatory responses in human neutrophils. The therapeutic potential of SB-EtOH was further assessed using a mouse model of lipopolysaccharide (LPS)-induced ARDS.</div></div><div><h3>Results</h3><div>SB-EtOH significantly inhibited respiratory burst, degranulation, and chemotactic responses in activated human neutrophils without cytotoxic effects. Additionally, SB-EtOH attenuated phosphorylation of key inflammatory signaling molecules, Akt and p38, while reducing calcium mobilization in activated human neutrophils. In the LPS-induced ARDS mouse model, SB-EtOH reduced pulmonary neutrophil infiltration, lung tissue damage, and oxidative stress accumulation.</div></div><div><h3>Conclusion</h3><div>These findings suggest that <em>S. barbata</em> is a promising therapeutic candidate for ARDS and other neutrophil-predominant inflammatory diseases by mitigating neutrophilic inflammation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119653"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692240","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}
引用次数: 0
Haizao Yuhu decoction ameliorates silica-induced lung injury by inhibiting transforming growth factor-beta1/Smad pathway
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119669
Rui Qian , Yunyi Xu , Luoning Zhang , Liqun Wang , Xuxi Chen , Mengzhu Wang , Qixue Bao , Yuqin Yao , Linshen Xie
{"title":"Haizao Yuhu decoction ameliorates silica-induced lung injury by inhibiting transforming growth factor-beta1/Smad pathway","authors":"Rui Qian ,&nbsp;Yunyi Xu ,&nbsp;Luoning Zhang ,&nbsp;Liqun Wang ,&nbsp;Xuxi Chen ,&nbsp;Mengzhu Wang ,&nbsp;Qixue Bao ,&nbsp;Yuqin Yao ,&nbsp;Linshen Xie","doi":"10.1016/j.jep.2025.119669","DOIUrl":"10.1016/j.jep.2025.119669","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Haizao Yuhu Decoction (HYD) is a traditional Chinese herbal formula known for regulating Qi and dispersing stasis.</div></div><div><h3>Aim of the study</h3><div>This study investigates the effects of HYD on silica-induced lung injury and the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The main constituents of HYD were identified using ultra-performance liquid chromatography Q-Exactive mass spectrometry (UPLC-QE-MS). Network pharmacology was employed to predict the targets and pathways through which HYD ameliorates silicosis, which were validated in a silica-induced lung injury mouse model and a TGF-β1-induced alveolar epithelial cell model. Pathological evaluation was conducted using hematoxylin-eosin (H&amp;E) and Masson staining, while inflammatory cytokines and fibrosis were assessed via enzyme-linked immunosorbent assay (ELISA) and hydroxyproline quantification. Western blotting (WB) was performed to analyse protein expression levels of targeted markers. Proliferation and migration capabilities of MLE12 cells treated with HYD and its bioactive constituents (glycitein, diosmetin, and limonin) were assessed using cell counting kit-8 (CCK-8) and wound healing assays.</div></div><div><h3>Results</h3><div>HYD significantly alleviated silica-induced lung injury, reducing inflammatory response and collagen deposition. A total of 176 constituents were identified in HYD, with 111 being pharmacologically active and linked to 1397 potential therapeutic targets, 107 associated with silicosis. Enrichment analyses highlighted the TGF-β1/Smad pathway and epithelial-mesenchymal transition (EMT) in HYD’s anti-silicosis effects, which was validated by the restoration of TGF-β1, p-Smad2/Smad2, p-Smad3/Smad3, E-cadherin, and Vimentin following HYD treatment. Additionally, glycitein, diosmetin, and limonin inhibited the proliferation and migration of TGF-β1-induced MLE12 cells and suppressed the activation of TGF-β1/Smad pathway and EMT.</div></div><div><h3>Conclusions</h3><div>HYD effectively alleviates silica-induced lung injury by specifically inhibiting the TGF-β1/Smad pathway and EMT process.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119669"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692337","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}
引用次数: 0
Xinyin tablets affect mitophagy and cardiomyocyte apoptosis to alleviate chronic heart failure by regulating histone deacetylase 3(HDAC3)-mediated PTEN induced putative kinase 1(PINK1)/Parkin signaling pathway.
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119666
Hanyu Chen, Qianbei Lin, Yanlin Zeng, Pinliang Chen, Pengpeng Guo, Ruoshui Feng, Zhenyu Guo, Jinhua Kang, Qiucen Chen, Xiaoxiong Zhou
{"title":"Xinyin tablets affect mitophagy and cardiomyocyte apoptosis to alleviate chronic heart failure by regulating histone deacetylase 3(HDAC3)-mediated PTEN induced putative kinase 1(PINK1)/Parkin signaling pathway.","authors":"Hanyu Chen, Qianbei Lin, Yanlin Zeng, Pinliang Chen, Pengpeng Guo, Ruoshui Feng, Zhenyu Guo, Jinhua Kang, Qiucen Chen, Xiaoxiong Zhou","doi":"10.1016/j.jep.2025.119666","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119666","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Xinyin, a Chinese patent medicine, is composed of Panax ginseng C.A.Mey. (Araliaceae), Ilex pubescens Hook. & Arn. (Aquifoliaceae), Leonurus japonicus Houtt. (Lamiaceae), Plantago asiatica L. (Plantaginaceae), Ophiopogon japonicus (Thunb.) Ker Gawl. (Asparagaceae), Astragalus membranaceus (Fisch.) Bunge, and Draba nemorosa L. (Brassicaceae). It has been used for the prevention and treatment of chronic heart failure (CHF) clinically. However, its underlying mechanism of action is far from completely understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This study aimed to determine whether Xinyin alleviates CHF in SPF C57 mice and to explore the potential mechanism of action in H9c2 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Liquid chromatography tandem mass spectroscopy (LC-MS/MS) was performed to identify the chemical compounds in Xinyin. In vivo, 60 C57 mice were randomly divided into 6 groups: the sham group; model group; low-, medium-, and high-dose Xinyin groups; and perindopril group. Animals in the sham group underwent thoracotomy only. The others were subjected to coronary artery ligation. After 4 weeks of drug intervention, the cardiac function of the mice in each group was detected via echocardiography, the myocardial cells were evaluated via HE staining, and the degree of myocardial fibrosis was detected via Masson's trichrome staining. The expression of PINK1/Parkin signaling pathway-related genes (HDAC3, PINK1, Parkin, P62, LC3II/I, caspase-3, caspase-9, and Bax) was analyzed via RT‒qPCR and Western blotting. The effects of Xinyin on cardiomyocyte apoptosis and mitophagy mediated by the HDAC3 and PINK1/Parkin pathways in CHF model mice were evaluated. In vitro, H9c2 cardiomyocytes subjected to hypoxia were treated with different concentrations of Xinyin. The mRNA transcription levels of HDAC3, PINK1, Parkin, P62, LC3II/I, caspase-3, caspase-9, and Bax were measured via fluorescence quantitative PCR. Western blotting was used to detect the protein expression levels of PINK1, Parkin, P62, LC3 II/I, caspase-3, caspase-9, and Bax. TUNEL staining was used to detect the number of apoptotic bodies in the myocardium to evaluate the level of apoptosis. Transmission electron microscopy was used to observe changes in the number of mitophagosomes. Rapamycin (mitophagy agonist), Mdivi-1 (mitophagy inhibitor), ITSA-1 (HDAC3 agonist) and RGFP966 (HDAC3 inhibitor) were used to create intervention conditions. The effects of rapamycin or Mdivi-1 on PINK1/Parkin-mediated mitophagy were observed. Then, the effects of HDAC3 on the PINK1/Parkin signaling pathway, mitophagy and apoptosis in hypoxic cardiomyocytes were observed. Hypoxic cardiomyocytes were treated with Xinyin-containing serum or control serum to observe whether Xinyin could still play a protective role in cardiomyocytes when HDAC3 is activated or mitophagy is inhibited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;785 compounds were characteri","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119666"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692241","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}
引用次数: 0
Corrigendum to "Longan Aril polysaccharides ameliorate cognitive impairment in AD mice via restoration of the immune phagocytosis of microglia" [J. Ethnopharmacol. 343 (2025) 119464].
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119662
Han Zhang, Fangxin Bi, Peng Zhao, Herong Cui, Xiaojun Tao, Jianghua Zhang, Chang Li, Yang Cao, Nan Wang, Hongyan Li
{"title":"Corrigendum to \"Longan Aril polysaccharides ameliorate cognitive impairment in AD mice via restoration of the immune phagocytosis of microglia\" [J. Ethnopharmacol. 343 (2025) 119464].","authors":"Han Zhang, Fangxin Bi, Peng Zhao, Herong Cui, Xiaojun Tao, Jianghua Zhang, Chang Li, Yang Cao, Nan Wang, Hongyan Li","doi":"10.1016/j.jep.2025.119662","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119662","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119662"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692323","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}
引用次数: 0
Effects of repeated administration for 28 Days of fixed oil from Syagrus coronata (Mart.) Becc. On toxicological patterns in mice
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119665
João Victor de Oliveira Alves , Bartira Victoria Dantas da Rocha Barbosa , Irivânia Fidelis da Silva Aguiar , Laís Ruanita Leopoldina Galvão , Julliano Matheus de Lima Maux , Jacinto da Costa Silva Neto , Alisson Macário de Oliveira , Thiago Henrique Napoleão , Maria Tereza dos Santos Correia , Wêndeo Kennedy Costa , Marcia Vanusa da Silva
{"title":"Effects of repeated administration for 28 Days of fixed oil from Syagrus coronata (Mart.) Becc. On toxicological patterns in mice","authors":"João Victor de Oliveira Alves ,&nbsp;Bartira Victoria Dantas da Rocha Barbosa ,&nbsp;Irivânia Fidelis da Silva Aguiar ,&nbsp;Laís Ruanita Leopoldina Galvão ,&nbsp;Julliano Matheus de Lima Maux ,&nbsp;Jacinto da Costa Silva Neto ,&nbsp;Alisson Macário de Oliveira ,&nbsp;Thiago Henrique Napoleão ,&nbsp;Maria Tereza dos Santos Correia ,&nbsp;Wêndeo Kennedy Costa ,&nbsp;Marcia Vanusa da Silva","doi":"10.1016/j.jep.2025.119665","DOIUrl":"10.1016/j.jep.2025.119665","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Syagrus coronata</em> (Mart.) Becc. is a plant traditionally used in medicine for its anti-inflammatory, anti-venom, antifungal, wound-healing, and pain-relieving properties, which served as the basis for this study.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the toxicity of repeated doses of <em>S. coronata</em> fixed oil (ScFO) over a 28-day period.</div></div><div><h3>Materials and methods</h3><div>Following OECD 407/2008 guidelines, the repeated-dose toxicity study assessed the effects of ScFO on motor function, exploratory behavior, hematological and biochemical parameters, histopathology, and oxidative stress.</div></div><div><h3>Results</h3><div>Behavioral tests indicated increased grooming and reduced exploration, suggesting potential anxiolytic and sedative effects. In the rotarod test, sex-dependent differences in motor coordination were noted, particularly in females. Hematological analysis showed leukocytosis at the 1000 mg/kg dose, indicative of an immune response to stress. Elevated hepatic and renal markers at 500 and 1000 mg/kg doses suggested possible organ damage, alongside a decrease in total cholesterol levels. No macroscopic changes in organ appearance were observed, and liver weights remained consistent across groups. Histopathological examination showed no significant tissue alterations. ScFO treatment reduced oxidative stress markers and enhanced antioxidant enzyme activity.</div></div><div><h3>Conclusions</h3><div>Although macroscopic and histopathological findings support the safety of ScFO, the adverse biochemical effects observed warrant caution with prolonged use. These results highlight the importance of comprehensive toxicity evaluations to fully understand the safety and therapeutic potential of novel compounds.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119665"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692333","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}
引用次数: 0
Citrus medica L. essential oil improves anxiety-like behaviors accompanied by fatigue through α7-nAChR receptor-mediated neuroprotection effects.
IF 4.8 2区 医学
Journal of ethnopharmacology Pub Date : 2025-03-21 DOI: 10.1016/j.jep.2025.119667
Yanyan Yang, Yonggui Song, Weize Xu, Zhifu Ai, Genhua Zhu, Ming Yang, Qin Zheng, Huanhua Xu, Yali Liu, Yuhui Ping, Dan Su
{"title":"Citrus medica L. essential oil improves anxiety-like behaviors accompanied by fatigue through α7-nAChR receptor-mediated neuroprotection effects.","authors":"Yanyan Yang, Yonggui Song, Weize Xu, Zhifu Ai, Genhua Zhu, Ming Yang, Qin Zheng, Huanhua Xu, Yali Liu, Yuhui Ping, Dan Su","doi":"10.1016/j.jep.2025.119667","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119667","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Citrus medica L. has been cultivated in China for over two thousand years, with the effects of soothing the liver, regulating qi. Studies have shown that it can relieve anxiety. Its combination with other traditional Chinese medicines has been widely used in clinical practice assist in the treatment of anxiety and depression. The essential oil rich in peel is important active substance of Citrus medica L. A large number of studies have confirmed that essential oils are commonly used to relieve pain, psychological stress and induce relaxation. However, there are currently no studies on the effects of Citrus medica L. essential oil (CEO) on anxiety.</p><p><strong>Aim of the study: </strong>Anxiety has become the most common mental illness worldwide, so effective and diverse prevention and control methods are urgently needed. The main objective of this study is to evaluate the therapeutic effect and optimal administration route of CEO on anxiety caused by different susceptibility factors, and to further explore its potential mechanism for improving anxiety, providing scientific guidance for the application of CEO.</p><p><strong>Materials and methods: </strong>Induce anxiety models caused by fatigue or stress, and use animal behavior as an indicator to evaluate the CEO. To illustrate the underlying mechanisms of anti-anxiety effect of CEO, histological examination, immunofluorescence staining and Western Blot were carried out.</p><p><strong>Results: </strong>The results showed that the safer inhalation administration was more effective. Compared with the stress-induced anxiety model, CEO has a more obvious effect on fatigue-induced anxiety. After CEO administration, the frequency, time, and movement distance of fatigue-type anxious mice in Open Field Test (OFT) increased significantly. During Elevated Plus Maze Test (EPM), the mice spent more time and have more entry in the open arm. Further research found that CEO can significantly increase cerebral blood flow, recover damaged neurons in the hippocampus. RNA-seq analysis investigated that CEO can significantly improve gene expression in the hippocampus of fatigue accompanied anxiety mice. The underlying mechanism is significantly related to cholinergic system pathways. Further research found that the alpha-7 nicotinic acetylcholine receptor (α7-nAChR) in anxious mice was down-regulated, accompanied by decreased activation of its downstream ERK/CREB. Inhaling essential oil improved fatigue-induced anxiety by reversing this phenomenon.</p><p><strong>Conclusions: </strong>The results demonstrated that CEO have a significant anti-anxiety effect, especially fatigue induced anxiety. Our research results verify the accuracy and effectiveness of symptomatic treatment strategies for anxiety caused by different susceptibility factors, and provide scientific guidance for the rational use of CEO.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119667"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692319","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}
引用次数: 0
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