Haonan Xu , Fang Zhang , Yan Che , Tingting Sun , Ke Che , Yu Cui , Niannian Zhou , Jun Wan , Wenlong Chang , Yueqin Guan , Yuying Huang , Hao Chen
{"title":"Thesium chinense Turcz. and its compound astragalin alleviate lipopolysaccharide-induced acute lung injury via the PI3K/AKT/p53 signaling pathway","authors":"Haonan Xu , Fang Zhang , Yan Che , Tingting Sun , Ke Che , Yu Cui , Niannian Zhou , Jun Wan , Wenlong Chang , Yueqin Guan , Yuying Huang , Hao Chen","doi":"10.1016/j.jep.2025.119691","DOIUrl":"10.1016/j.jep.2025.119691","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Thesium chinense</em> Turcz. (TCT) is a traditional Chinese medicinal plant commonly used in clinical practice for respiratory diseases, known for its anti-inflammatory and antioxidant properties. However, the mechanisms by which TCT alleviates acute lung injury (ALI) remain not fully understood.</div><div>Aim of the study: This study aims to validate the efficacy and elucidate the mechanisms of TCT in the treating ALI through experimental and network pharmacology approaches.</div></div><div><h3>Materials and methods</h3><div>To find the bioactive substances in TCT, ultra-high-performance liquid chromatography in conjunction with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) was employed. The therapeutic effects of TCT were assessed by oxidative stress assessments, histological analysis (HE staining), inflammatory cytokine evaluations (RT-qPCR, immunofluorescence, immunohistochemistry), and TUNEL apoptotic staining in mice with lipopolysaccharide-induced ALI models. TP53 was identified as a crucial therapeutic target and astragalin as a pivotal drug by network pharmacology analysis. Their binding properties were verified by molecular dynamics simulations using GROMACS. The effects of astragalin on cell apoptosis (flow cytometry), cytokine expression (RT-qPCR), and protein expression (Western blot) were examined in <em>vitro</em> using LPS-stimulated RAW264.7 macrophages.</div></div><div><h3>Results</h3><div>In TCT, 24 key bioactive chemicals were found using UHPLC-QE-MS. TCT significantly reduced LPS-induced ALI, decreased levels of inflammatory cytokines TNF-α, IL-6, and IL-1β, decreased NFκB expression, increased superoxide dismutase (SOD) activity, decreased malondialdehyde (MDA) content, and reduced lung tissue cell apoptosis, according to the pharmacological results. The PI3K/AKT/p53 signaling pathway is essential for treating ALI, and astragalin was identified as the main drug and TP53 as the critical target by network pharmacology analysis. Strong binding and stability between astragalin and TP53 were demonstrated by molecular docking and dynamics simulations. Astragalin dramatically decreased early and late apoptosis, blocked p-PI3K and p-AKT activation, activated p53, and repressed the production of TNF-α, IL-6, and IL-1β <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>This study suggests that TCT and its active compound astragalin alleviate LPS-induced ALI by modulating the PI3K/AKT/p53 signaling pathway, offering a potential therapeutic approach for treating ALI.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119691"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697430","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}
Tianyuan Liu , Yage Liu , Hanfen Shi , Gaiyue Yue , Xuan Dai , Yueyi Zhang , Shan Wang , Jin Shen , Tianshu Xu , Jiyuan Yin , Jianglan Zhang , Yanfei Zhang , Lili Wang , Gang Zhou , Dongwei Zhang
{"title":"Sijunzi decoction improves lipid metabolism via regulation of Wnt/β-catenin signaling pathway in diabetic mice and 3T3-L1 cells","authors":"Tianyuan Liu , Yage Liu , Hanfen Shi , Gaiyue Yue , Xuan Dai , Yueyi Zhang , Shan Wang , Jin Shen , Tianshu Xu , Jiyuan Yin , Jianglan Zhang , Yanfei Zhang , Lili Wang , Gang Zhou , Dongwei Zhang","doi":"10.1016/j.jep.2025.119672","DOIUrl":"10.1016/j.jep.2025.119672","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Sijunzi decoction (SJZD), a traditional Chinese medicinal formula with the functions of invigorating the Spleen and replenishing Qi, has been clinically used for the management of diabetes, but its actions and underlying mechanisms on diabetic lipid metabolism remain largely unknown.</div></div><div><h3>Aim of the study</h3><div>To explore the effects of SJZD on lipid metabolism disorders and its association with the Wnt/β-catenin pathway in the white adipose tissue of diabetic mice and 3T3-L1 cells.</div></div><div><h3>Materials and methods</h3><div>The diabetic lipid metabolism disorders models were established by high-fat diet/streptozotocin in mice and palmitic acid in 3T3-L1 cells, respectively. The effects of SJZD on total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and glucose consumption were determined by biochemical assay. Hematoxylin-eosin (H&E) staining was used to examine pathological alterations in adipose tissues. Oil red O staining was used to evaluate the differentiation of lipid droplets in 3T3-L1 adipocytes. The expression levels of Wnt10b, β-catenin, CCAAT enhancer binding protein α (C/EBP-α), sterol regulatory element-binding protein 1 (SREBP-1c), acetyl-CoA carboxylase-1 (ACC1), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase (FASN), adipose triglyceride lipase (ATGL) were examined by Western blot and/or qRT-PCR. In addition, the main components of SJZD and SJZD-containing serum (SCS) were identified by UPLC-Q-TOF-MS/MS.</div></div><div><h3>Results</h3><div>SJZD reduces the body fat ratio, fasting blood glucose levels, adipose tissue index and serum levels of TC, TG, and LDL, and increases the body weight, lean ratio, and serum HDL levels, as well as prevents the adipocytes hypertrophy in diabetic mice. In addition, SJZD, SCS and its ingredients (Ginsenoside Rb1 and Glycyrrhetinic acid) inhibit lipid synthesis, TG levels and promote glucose consumption in diabetic mice and 3T3-L1 adipocytes. These interventions decrease the expressions of PPAR-γ, SREBP-1c, C/EBP-α, FASN, ACC1 and P-β-catenin, and increase the expressions of ATGL, Wnt10b and β-catenin.</div></div><div><h3>Conclusion</h3><div>SJZD regulates the Wnt/β-catenin signaling pathway to preserve lipid metabolism homeostasis in diabetes. GRb and Gac may constitute the material basis of SJZD in attenuation of diabetic lipid metabolism disorders. These findings highlight a novel strategy for the treatment of diabetes.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119672"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730213","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}
Yuqin Zhang , Yonghua Ye , Xuezhen Li , Min Guo , Chenxi Zhuo , Wenting Chen , Xiaoxue Zou , Yaping Chen , Lihong Nan , Lixia Chen , Hua Li
{"title":"Inhibition of oxidative stress contributes to the protective effect of Herba Siegesbeckiae on ischemic stroke by PI3K/STAT3/FOXO3a signal axis","authors":"Yuqin Zhang , Yonghua Ye , Xuezhen Li , Min Guo , Chenxi Zhuo , Wenting Chen , Xiaoxue Zou , Yaping Chen , Lihong Nan , Lixia Chen , Hua Li","doi":"10.1016/j.jep.2025.119688","DOIUrl":"10.1016/j.jep.2025.119688","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Herba Siegesbeckiae (HS), well-recognized among the commonly used traditional medicines, is popular as one of the in-clinic treatments for rheumatoid arthritis, ischemic stroke, paralysis, asthma, and allergic disorders. However, the underlying mechanisms of neuroprotection and the part played by HS in protection against neuronal apoptosis continue to be nebulous.</div></div><div><h3>Aim of the study</h3><div>This study aims to explore whether HS can alleviate cerebral ischemic injury by protecting neurons and alleviating oxidative stress injury, and to elucidate the molecular mechanisms involved in PI3K/STAT3/FOXO3a signal pathway.</div></div><div><h3>Methods</h3><div>In this study, both <em>in vitro</em> and <em>in vivo</em> experiments were performed to examine the neuroprotective effects of HS on oxidative stress injury and neuronal apoptosis. After the HS treatment, several assays were done to assess the neuroprotection, oxidative stress response, and neuronal apoptosis. Besides, to further clarify the role of HS on the PI3K/STAT3/FOXO3a signal pathway, the effects of combining the HS with an inhibitor, agonist, or siRNA were studied.</div></div><div><h3>Results</h3><div>From the <em>in vivo</em> and <em>in vitro</em> experiments, it was evident that HS inhibited neuronal apoptosis to a significant degree and offered effective protection against oxidative stress injury by lowering the concentration of the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). Moreover, HS obviously up-regulated the principal proteins expression of the PI3K/STAT3/FOXO3a signal pathway, including the PI3K, p-Akt/Akt, and p-FOXO3a/FOXO3a. Additionally, HS reduced the fluorescence intensity of the STAT3 and FOXO3a, and advanced their nuclear translocation both in the <em>in vitro</em> and <em>in vivo</em> models. Nevertheless, after the combined treatment with HS and LY294002, Colivelin or siRNA-FOXO3a, these effects were reversed.</div></div><div><h3>Conclusions</h3><div>The present study gives pharmacological evidence, revealing that HS wields its protective actions by regulating the PI3K/STAT3/FOXO3a signal pathway, thus inhibiting oxidative stress injury and protecting the neurons from oxidative stress-generated damage. The current study emphasizes the potential of HS as a therapeutic means of treatment of oxidative stress conditions related to ischemic stroke.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119688"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697429","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}
Min Bai, Zhichao Zhou, Mei Yin, Mei Wang, Xiaoping Gao, Jiaqing Zhao
{"title":"Corrigendum to \"The use of metagenomic and untargeted metabolomics in the analysis of the effects of the Lycium barbarum glycopeptide on allergic airway inflammation induced by Artemesia annua pollen\" [J. Ethnopharmacol. (2025) 337(Pt 1) 118816].","authors":"Min Bai, Zhichao Zhou, Mei Yin, Mei Wang, Xiaoping Gao, Jiaqing Zhao","doi":"10.1016/j.jep.2025.119657","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119657","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119657"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700514","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}
Ming Zhang , Minmin Chen , Yizhe Yan , Juan Lu , Jun Sheng , Mingying Gui , Xiao Ma
{"title":"Comprehensive characterisation of bioactive compounds in Boletus edulis as functional foods to improve muscle atrophy; through whole plant targeted metabolomics, network pharmacology, in vivo and in vitro experiments, molecular docking and molecular dynamics analysis","authors":"Ming Zhang , Minmin Chen , Yizhe Yan , Juan Lu , Jun Sheng , Mingying Gui , Xiao Ma","doi":"10.1016/j.jep.2025.119685","DOIUrl":"10.1016/j.jep.2025.119685","url":null,"abstract":"<div><h3>Ethnopharmacological significance</h3><div>Boletus edulis (BE) is a naturally occurring fungus that has been traditionally used in ancient Chinese herbal medicine. It is a key component of the formula ‘Shujin Pill’, commonly prescribed for the treatment or relief of muscular dystrophy. However, the specific efficacy of BE within Shujin Pill or its primary active components remains unclear.</div></div><div><h3>Aims of the study</h3><div>This study aims to elucidate the biological function and molecular mechanisms of BE in alleviating muscular atrophy in mice. We employed a comprehensive approach, integrating metabolomics, network pharmacological analysis, molecular docking, molecular dynamics simulation, and in <em>vivo</em> and in vitro experimental validation, to verify these effects.</div></div><div><h3>Materials and methods</h3><div>The bioactive components in BE were quantified by UPLC-QTOF-MS/MS. To evaluate the muscle function indexes after 14 days of action of different doses of BE and to analyze the pathological changes in muscle tissue. Enabling network pharmacology to analyze the potential active components in BE for the alleviation of muscle atrophy, using computer molecular simulation for docking scores, molecular dynamics simulation to assist in the validation of the active components in BE, and in <em>vitro</em> experiments for the validation of the active components.</div></div><div><h3>Result</h3><div>BE administered alone was able to slow down Lipopolysaccharide (LPS)-induced muscle atrophy. 996 non-volatile components were detected in BE by metabolomics, and GAPDH, TP53, AKT1, TNF-α and IL-6 were more strongly associated with muscle atrophy by using web-based pharmacological analyses. Folic acid, Cycloartenol and Sesamin active ingredients have greater potential to treat or alleviate muscle atrophy, molecular docking, molecular dynamics detected that Sesamin and AKT both have high binding energy, in <em>vitro</em> using C2C12 skeletal muscle cells to verify the efficacy of Sesamin and BE, found that in the presence of the LY294002 (PI3K inhibitor) and GSK21417 (AKT inhibitor) treatment conditions, the elimination of the up-regulation of the PI3K/AKT signaling pathway by Sesamin and BE and loss of biological efficacy. It suggests that BE may slow down or treat muscle atrophy through the PI3K/AKT signaling pathway, in which Sesamin plays a major role. Meanwhile BE and Sesamin were able to enhance the antioxidant level of C2C12 skeletal muscle cells.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119685"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating metabolomics and network pharmacology to study the mechanism of Er-Xian decoction in improving intervertebral disc degeneration","authors":"Xiaobo Wang, Guoqiang Ren, Binhui Chen","doi":"10.1016/j.jep.2025.119702","DOIUrl":"10.1016/j.jep.2025.119702","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Intervertebral disc degeneration (IDD) is the progressive deterioration of the structure and function of an intervertebral disc (IVD), which manifests as excessive catabolism of the IVD extracellular matrix, which may lead to the gradual loss of IVD proteoglycans and water, thus altering the IVD composition and eventually leading to degeneration. As a traditional Chinese medicine, Er-Xian decoction (EXD) can balance the body's yin and yang, tonify the liver and kidney, invigorate blood circulation, and prevent blood stasis. Pharmacological research has shown that EXD regulates antioxidant and endocrine metabolism, maintains immune balance, and improves microcirculation.</div></div><div><h3>Aims of the study</h3><div>To clarify the efficacy of EXD on treating IDD.</div></div><div><h3>Materials and methods</h3><div>Serum was collected from model IDD rabbits treated with EXD for metabolomics analysis, and its mechanism of action was predicted on the basis of the metabolomics and network pharmacology data. Nucleus pulposus cells (NPCs) were induced with IL-1β to build an <em>in vitro</em> IDD model, and EXD was administered along with an inhibitor. All groups of cells were subjected to CCK-8 assays, ELISA and flow cytometry, immunohistochemistry, Western blot, and immunofluorescence staining analyses to explore how EXD protects NPCs and the underlying mechanism.</div></div><div><h3>Results</h3><div>EXD reduced inflammatory processes, restored IVD height, and alleviated IDD in rabbits. Integrated metabolomics and network pharmacology analyses revealed that EXD exerts its therapeutic effects on IDD primarily via the mTOR and HIF-1 signalling pathways, and the active components of EXD, including anhydroicaritin, β-sitosterol, kaempferol, quercetin, and stigmasterol, bound strongly to pivotal targets within these pathways. Moreover, EXD reduced the inflammatory factor levels, inhibited NPC apoptosis, and upregulated the key proteins p-mTOR, HIF-1α, and p-AKT. Conversely, the HIF-1 inhibitor BAY872243 increased the inflammatory factor levels and led to NPC deterioration.</div></div><div><h3>Conclusion</h3><div>EXD regulates disc cell metabolism and inflammatory responses by modulating the mTOR and HIF-1 signalling pathways, thereby slowing or reversing IDD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119702"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730163","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}
Wang Ya-Zhu, Wang Xiao-Ting, Tian Shu-Qing, Jia Tian-Zhu, Gao Hui
{"title":"Discussion on the effects of Chinese medicine processing on the changes of medicinal properties based on the changes of chemical constituents and pharmacodynamic perspective.","authors":"Wang Ya-Zhu, Wang Xiao-Ting, Tian Shu-Qing, Jia Tian-Zhu, Gao Hui","doi":"10.1016/j.jep.2025.119687","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119687","url":null,"abstract":"<p><strong>Ethnopharmacology relevance: </strong>The theory of medicinal properties in Traditional Chinese Medicine (TCM) has a long history and serves as the foundation and core of TCM's theoretical system. It plays an irreplaceable role in guiding clinical medication and enhancing therapeutic efficacy. TCM processing is a traditional technology for processing and treating Chinese medicinal materials, which is a major characteristic of clinical TCM practice. Through processing, the chemical components and pharmacological effects of Chinese medicinal materials will change, manifested as changes in several aspects of their medicinal properties. These changes lead to corresponding alterations in their therapeutic functions and clinical applications, enabling them to meet diverse clinical needs for treating various diseases and conditions.</p><p><strong>Aims of the study: </strong>This study begins with an exploration of ancient books on the relationship between TCM processing and medicinal properties. It aims to provide a modern scientific basis for clarifying how processing affects TCM's medicinal properties, while offering a systematic interpretation of traditional theories through the lens of chemical composition and pharmacological changes.</p><p><strong>Materials and methods: </strong>We collected and analyzed relevant articles from different scientific databases regarding TCM processing and medicinal properties theory. By concentrating on well-studied TCM varieties as representatives, the effects of processing on the changes of medicinal properties of TCM were explained by examples from the perspective of chemical composition and pharmacodynamic changes.</p><p><strong>Results: </strong>The findings of this study indicate that analyzing the impact of TCM processing on its medicinal properties not only enhances the application of TCM but also serves as a crucial reference for the development of new pharmaceuticals. In addition, the study reveals the complexity of the changes in the characteristics of TCM, which brings new challenges and opportunities for further research. Especially in the perspective of modern pharmacology, in-depth study of the relationship between the processing of TCM and its efficacy will provide a scientific basis for the standardization and normalization of TCM.</p><p><strong>Conclusion: </strong>This study enriches the theoretical framework of TCM processing and establishes an empirical foundation for optimizing its clinical use. We hope that these findings will stimulate further research, so as to promote the modernization of TCM, which will lay a more solid foundation for the scientific research and clinical application of TCM.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119687"},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700467","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}
Yahui Dong, Yang Liu, Jie Tang, Jiahui Du, Xuzhen Zhuang, Song Tan, Ye Yang, Dengke Yin
{"title":"Corrigendum to \"Zhisou powder displays therapeutic effect on chronic bronchitis through inhibiting PI3K/Akt/HIF-1α/VEGFA signaling pathway and reprograming metabolic pathway of arachidonic acid\" [J. Ethnopharmacol. 319 (2024) 117110].","authors":"Yahui Dong, Yang Liu, Jie Tang, Jiahui Du, Xuzhen Zhuang, Song Tan, Ye Yang, Dengke Yin","doi":"10.1016/j.jep.2025.119660","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119660","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119660"},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692325","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}
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}