Xinyu Zhang , Zhangxin Ji , Qing He , Dongmei Yang , Xueyang Wang , Conghui Liu , Chuanqi Zhang , Jingjing Yuan , Na Xu , Jun Chu
{"title":"Gegen Qinlian Decoction inhibits liver ferroptosis in type 2 diabetes mellitus models by targeting Nrf2","authors":"Xinyu Zhang , Zhangxin Ji , Qing He , Dongmei Yang , Xueyang Wang , Conghui Liu , Chuanqi Zhang , Jingjing Yuan , Na Xu , Jun Chu","doi":"10.1016/j.jep.2024.119290","DOIUrl":"10.1016/j.jep.2024.119290","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Type 2 diabetes mellitus (T2DM) is a metabolic disease that can lead to complications affecting multiple organs, including the liver. Gegen Qinlian Decoction (GQD) has demonstrated considerable efficacy in the management of T2DM and its complications in accordance with the tenets of modern Chinese medicine. However, the molecular mechanism by which GQD alleviates diabetic liver injury is unclear.</div></div><div><h3>Aim of the study</h3><div>To explore the effect and mechanism of GQD to ameliorate liver injury in T2DM.</div></div><div><h3>Materials and methods</h3><div>The active constituents of GQD were analyzed using UPLC. An in vivo T2DM mouse model was established by 6 weeks of high-fat diet and multiple streptozotocin (50 mg/kg/day) induction, followed by GQD administration. The evaluation of liver function, histopathology, oxidative stress, lipid peroxidation, and iron levels was conducted. In vitro experiments involved a high-glucose-induced AML12 cell model to assess oxidative stress, lipid peroxidation, and iron levels.</div></div><div><h3>Results</h3><div>UPLC identified four main components in GQD: puerarin, baicalin, berberine and liquiritin. GQD administration resulted in enhanced liver function and a reduction in injury, accompanied by elevated antioxidant enzyme activity, increased GPX4 expression and diminished reactive oxygen species in T2DM mice. GQD treatment reduced lipid peroxidation and regulated iron transport proteins, thereby alleviating iron overload. In AML12 cells, GQD administration resulted in regulated mitochondrial morphology.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrated that GQD ameliorated liver injury in T2DM by inhibiting ferroptosis through the modulation of Nrf2.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119290"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894991","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}
Haiyang Zhao , Jinwang Mei , Qianqian Huang , Hui Wang , Zhaohui Xu
{"title":"Research progress of main components from Epimedii Folium (Yinyanghuo) in the treatment of male reproductive dysfunction and application & development status of Epimedii Folium","authors":"Haiyang Zhao , Jinwang Mei , Qianqian Huang , Hui Wang , Zhaohui Xu","doi":"10.1016/j.jep.2024.119161","DOIUrl":"10.1016/j.jep.2024.119161","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Epimedii Folium (<em>Yinyanghuo</em>) is a commonly used Chinese herb that plays a significant role in a lot of herbal formulae used to treat sexual dysfunction. Recently, an increasing amount of research on Epimedii Folium related to male reproductive dysfunction has been reported, and the exploration and application of <em>Epimedium</em> are also expanding rapidly. Flavonoids make up the vast majority of the chemical composition of Epimedii Folium, with small amounts of icarsides series, alkaloids, polysaccharide, volatile oils and other natural compounds. Among them, icariin (ICA) has the highest concentration and the most potent effects on male reproductive dysfunction, icariin II (ICA II), total flavones and polysaccharides from <em>Epimedium</em> have also been reported.</div></div><div><h3>Aim of study</h3><div>In this review, we focus on the research progress of the main components from Epimedii Folium in the treatment of male reproductive dysfunction, as well as the application and development status of Epimedii Folium in China, aiming to provide ideas for future in-depth research and product development of Epimedii Folium.</div></div><div><h3>Methods</h3><div>On the one hand, we collected literature published from 2003 to May 2024 from various databases, including China National Knowledge Infrastructure (CNKI), the Database of Chinese Sci-Tech Periodicals (VIP), Wanfang Database, Web of Science, Elsevier ScienceDirect, SpringerLink, and the National Center for Biotechnology Information (NCBI) of the USA. On the other hand, we retrieved the data query system of the National Medical Products Administration, Special Food Information Query Platform of the State Administration for Market Regulation, Yaozhi.com, Baidu, China Patent Net, as well as JD.com and Tmall, categorized all epimedia-related products sold in China into medicine, health food, dietary supplements, and animal feed.</div></div><div><h3>Results</h3><div>A total of 3578 studies were obtained, of which 161 were selected for further analysis. Subsequently, the current status of the main components of Epimedii Folium in the treatment of male reproductive dysfunction was summarized in three sections: research progress on the chemical components of <em>Epimedium</em>, research progress on the pharmacological effects and mechanisms of the main active ingredients, and development and application of the main ingredients of <em>Epimedium</em>.</div></div><div><h3>Conclusion</h3><div>The flavonoids in Epimedii Folium have a beneficial effect on male reproductive dysfunction. However, to date, the primary components of Epimedii Folium have not been directly developed into clinical drugs for treating this condition. This may be due to the lack of a systematic evaluation of their safety. In the field of dietary supplements, products developed using Epimedii Folium as raw materials often face challenges such as low added value and limited in","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119161"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750989","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}
Xinyu Ge , Zhaochen Ma , Wenjing Wei , Huaijue Deng , Shuhui Tang , Yefeng Han , Yifan Li , Xiaofang He , Mingxiao Li , Na Lin , Houkai Li , Yanqiong Zhang , Lili Sheng
{"title":"Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis","authors":"Xinyu Ge , Zhaochen Ma , Wenjing Wei , Huaijue Deng , Shuhui Tang , Yefeng Han , Yifan Li , Xiaofang He , Mingxiao Li , Na Lin , Houkai Li , Yanqiong Zhang , Lili Sheng","doi":"10.1016/j.jep.2024.119176","DOIUrl":"10.1016/j.jep.2024.119176","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Quanduzhong capsule (QDZ), derived from <em>Eucommia ulmoides</em> Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.</div></div><div><h3>Materials and methods</h3><div>Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.</div></div><div><h3>Results</h3><div>Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.</div></div><div><h3>Conclusions</h3><div>Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119176"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769386","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-Hang Dou, Jia-Yi Huang, Peng-Yue Li, Wan-Ling Chen, Xin-Ran Wang, Tian-Zi Yang, Xiao-Yu Fan, Xin-Yu Zhang, Yang Lu, Jie Bai, Shou-Ying Du
{"title":"How can traditional Chinese medicine enhance the efficacy of antibiotics in the treatment of MRSA-infected pneumonia: An experimental study on the combination of Reyanning mixture (RYN) and linezolid","authors":"Min-Hang Dou, Jia-Yi Huang, Peng-Yue Li, Wan-Ling Chen, Xin-Ran Wang, Tian-Zi Yang, Xiao-Yu Fan, Xin-Yu Zhang, Yang Lu, Jie Bai, Shou-Ying Du","doi":"10.1016/j.jep.2024.119221","DOIUrl":"10.1016/j.jep.2024.119221","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Reyanning Mixture (RYN) is a Chinese patent medicine widely used in the treatment of respiratory inflammatory diseases in China and has potential in the treatment of bacteria-infected pneumonia.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to demonstrate the therapeutic potential of RYN in combination with linezolid for the treatment of MRSA-infected pneumonia and to explore the mechanisms of action and active components.</div></div><div><h3>Materials and methods</h3><div>The pharmacodynamics of RYN alone and in combination with linezolid was investigated in a rat model of MRSA-induced pneumonia. Transcriptomics, ELISA, Western blot and qRT-PCR were used to explore and verify the pharmacological mechanism of the anti-inflammatory effect of RYN. UPLC-MS and molecular docking were used to explore the anti-inflammatory components of RYN for the treatment of MRSA-infected pneumonia.</div></div><div><h3>Results</h3><div><em>In vivo</em>, RYN reduced lung injury and inflammation in rats with pneumonia. In particular, the combination of RYN and linezolid enhanced the therapeutic effect compared to that of either treatment alone. Further research suggests that the synergistic therapeutic effect of the combination may be related to the inhibition of the inflammatory response by RYN and the enhancement of linezolid inhibition and clearance of MRSA in lung tissues by RYN. RYN plays an anti-inflammatory role in MRSA-infected pneumonia by inhibiting the TLR2/NF-κB/NLRP3 pathway, with 7 active components that may play a dominant role.</div></div><div><h3>Conclusions</h3><div>These results indicate that RYN may serve as an adjuvant drug to antibiotics for the treatment of MRSA-associated pneumonia. Exploration of its mechanisms and active components is conducive to the clinical application and quality improvement of RYN. More importantly, this study showed that the synergistic therapeutic effect of the combination of traditional Chinese medicine and antibiotics may be a valuable therapeutic strategy.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119221"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801076","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}
Gang Wang , Yifan Yin , Rui Lv , Xiumei Ling , Houkang Cao , Haiping Liu , Jianzhao Wu , Ya Gao , Kefeng Zhang , Yongwang Wang
{"title":"Taraxasterol extracted from Ixeridium gramineum (Fisch.) Tzvel. Attenuated D-GalN/LPS-induced fulminant hepatitis by modulating the JAK/STAT and TNF signalling pathways","authors":"Gang Wang , Yifan Yin , Rui Lv , Xiumei Ling , Houkang Cao , Haiping Liu , Jianzhao Wu , Ya Gao , Kefeng Zhang , Yongwang Wang","doi":"10.1016/j.jep.2024.119256","DOIUrl":"10.1016/j.jep.2024.119256","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Taraxasterol (TAR), a compound highly abundant and easily obtainable from Tibetan medicine <em>Ixeridium gramineum</em> (Fisch.) Tzvel., exhibits a variety of biological effects, including hepatoprotective, anti-inflammatory, and antioxidant activities.</div></div><div><h3>Aim of the study</h3><div>To investigated the protective role and underlying mechanisms of TAR in fulminant hepatitis (FH) through the regulation of oxidative stress, inflammatory responses, and apoptosis by modulating the JAK/STAT and TNF signalling pathways.</div></div><div><h3>Material and methods</h3><div>The study used Kunming mice to establish a D-GalN/LPS-induced FH model, which was divided into the following groups: Control group, D-GalN/LPS group, D-GalN/LPS + Silymarin group, D-GalN/LPS + TAR 2.5 group, D-GalN/LPS + TAR 5 group, D-GalN/LPS + TAR 10 group, and TAR 10 group. H&E staining and biochemical analyses were employed to evaluate liver pathological changes. Oxidative stress factors and inflammatory response were assessed via ELISA. RNA sequencing analysis was used to detect changes in inflammatory factor genes and apoptosis genes with TAR intervention in liver tissues. The distribution of the proteins p-STAT3 and p-JNK in liver tissues was ascertained using immunohistochemical staining. <em>In vitro</em> experiments were conducted on RAW264.7 cells exposed to LPS and TAR. Apoptosis was evaluated via flow cytometry and Hoechst 33258 staining. Immunofluorescence staining was employed to determine the protein expression levels of p-STAT3 and p-JNK in RAW264.7 cells. Gene and protein expression in the JAK/STAT and TNF signalling pathways, as well as apoptosis, were analyzed using qRT-PCR and Western blotting.</div></div><div><h3>Results</h3><div>TAR effectively reduced hepatocyte necrosis, diminished inflammatory factor release, inhibited oxidative stress, significantly decreased the apoptosis of RAW264.7 cells, inhibited the protein expressions of p-JAK2, p-STAT3, p-MEK4, p-JNK, Caspase-3, Caspase-8, and Bax, and increased the protein expressions of SOCS3 and Bcl-2.</div></div><div><h3>Conclusion</h3><div>TAR prevents D-GalN/LPS-induced FH by regulating the JAK/STAT and TNF signalling pathways and apoptosis, demonstrating its therapeutic potential in treating liver diseases.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119256"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864411","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}
Si-si Liu , Zheng Zha , Chen Li , Chun-yu Li , Lei Wang
{"title":"The mechanism of exosomes of BMSCs modified with Bu Shen Yi Sui capsule in promoting remyelination via regulating miR-15b/Wnt signaling pathway-mediated differentiation of oligodendrocytes","authors":"Si-si Liu , Zheng Zha , Chen Li , Chun-yu Li , Lei Wang","doi":"10.1016/j.jep.2024.119283","DOIUrl":"10.1016/j.jep.2024.119283","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Bu Shen Yi Sui capsule (BSYS), a modified version of the classical Chinese medicine formula Liu Wei Di Huang pill, has demonstrated therapeutic efficacy in the treatment of multiple sclerosis (MS). Nevertheless, the precise mechanism through which BSYS facilitates remyelination remains to be elucidated.</div></div><div><h3>Aim of the study</h3><div>This research investigates the role and potential mechanisms of BSYS-modified exosomes (exos) derived from bone marrow mesenchymal stem cells (BMSCs) in promoting remyelination in a cuprizone (CPZ)-induced demyelination model in mice.</div></div><div><h3>Materials and methods</h3><div>C57BL/6J mice were administered a 0.2% CPZ-containing diet for 5 weeks to induce demyelination, followed by treatment with exosomes derived from BMSC (BMSC-exos) and BSYS-modified BMSC exosomes (BSYS-BMSC-exos) twice weekly for 2 weeks. Body weight measurements were recorded, and motor function was evaluated using the rotarod test. Pathological changes in myelin and axons were assessed <em>via</em> Luxol fast blue (LFB) staining, transmission electron microscopy (TEM), and immunofluorescence (IF) staining. Oligodendrocyte proliferation, differentiation, and maturation were analyzed using IF double-staining, Western blot (WB), and real-time quantitative reverse transcription PCR (qRT-PCR). Additionally, microRNA (miRNA) sequencing and a luciferase reporter assay were conducted to verify miRNA binding to its target gene. Key markers of the Wnt/β-catenin signaling pathway were examined using WB and qRT-PCR.</div></div><div><h3>Results</h3><div>BSYS-BMSC-exos treatment significantly increased both body weight and rotarod performance in CPZ mice. Moreover, BMSC-exos and BSYS-BMSC-exos reversed myelin loss and axonal damage. These treatments enhanced oligodendrocytes proliferation, differentiation, and maturation, with BSYS-BMSC-exos exhibiting a particularly pronounced effect on the expression of adenomatous polyposis coli clone CC1 (CC1), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and myelin basic protein (MBP). Sequencing and luciferase assays revealed that miR-15b-5p, enriched in BSYS-BMSC-exos, directly targets Wnt3a. Furthermore, BSYS-BMSC-exos elevated axis inhibition protein 2 (Axin2) expression while markedly reducing Wnt family member 3A (Wnt3a), phospho-glycogen synthase kinase-3β (p-GSK3β), β-catenin, and T-cell specific transcription factor 4/transcription factor 7-like 2 (TCF4/TCF7L2) levels.</div></div><div><h3>Conclusions</h3><div>The findings suggest that BSYS-BMSC-exos alleviate neurological deficits, enhance oligodendrocytes differentiation and maturation, and promote remyelination in CPZ mice. miR-15b-5p, enriched in BSYS-BMSC-exos, targets and downregulates Wnt3a, thereby inhibiting the Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119283"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903221","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":"Rescue of CUMS-induced HPA axis hyperfunction and hypothalamic synaptic deficits by Citrus aurantium L. cv. Daidai essential oil via the cAMP/PKA/Grin2b pathway.","authors":"Ze-Yu Zhang, Yu-Fei Liu, Si-Jia Zhang, Pan-Pan Zhang, Xiao-Xia Shen, Ji-Le Lan, Zhu-Jun Mao, Min-Jia Zhang, Ye-Ping Ruan, Xin Zhang","doi":"10.1016/j.jep.2025.119423","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119423","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Traditional Chinese medicine has historically used Citrus aurantium L. cv. Daidai to alleviate anxiety and improve mood. Essential oils are the primary active component of Citrus aurantium L. cv. Daidai, but little research has been conducted on the active substances and mechanisms of the antidepressant effect of Citrus aurantium L. cv. Daidai essential oil (CEO).</p><p><strong>Aim of the study: </strong>This research used network pharmacology, molecular docking, transcriptomics, and in vitro and in vivo experimental validation to assess the effectiveness and therapeutic mechanism of CEO.</p><p><strong>Materials and methods: </strong>We used gas chromatography‒mass spectrometry(GC-MS) to identify and quantify CEO components and brain-penetrating chemicals. CEO was given to chronic and unpredictable mild stimulation (CUMS) mice for 4 weeks. Depression was assessed using sucrose preference, forced swimming, tail suspension, elevated plus-maze, and open field tests. Analyzing brain homogenates and serum biochemistry data simultaneously revealed neurotransmitter and hormone alterations. Tissue samples were collected for histological and protein analysis. Furthermore, transcriptome and network pharmacology were used to investigate the mechanism by which CEO alleviates depression, and in vitro glutamate(Glu)-induced PC12 cell injury assays were conducted to validate this new mechanism.</p><p><strong>Results: </strong>CEO inhalation altered neurotransmitter and hormone expression and improved CUMS-induced weight and depression-like behavior in mice. Compared with CUMS mice, CEO mice presented less pathological brain damage, as demonstrated by HE staining, immunohistochemistry, Golgi staining, transmission electron microscopy, and immunofluorescence staining. We discovered that 13 of the active chemicals in CEO act on 522 targets, 96 of which are linked to depression. PRKACA was identified as the core target by a modular analysis of the PPI network. Network pharmacology and transcriptomics revealed that CEO influences depression via the cAMP/PKA/Grin2b pathway and Glu synaptic modulation. In vivo studies indicated that CEO administration reduced PKA and Grin2b phosphorylation in CUMS mice, inhibited the cAMP/PKA/Grin2b pathway, protected against synaptic deficits, and restored HPA axis function. In vitro investigations revealed that the survival rate of PC12 cells treated with CEO increased, the apoptotic rate decreased, and the expression of LDH, Ca<sup>2+</sup>, and MDA decreased. Western blot and immunofluorescence staining indicated that CEO inhibits the cAMP/PKA/Grin2b pathway to regulate Glu-induced PC12 cells and that 8-Bromo-cAMP pretreatment reduces the protective effect of CEO.</p><p><strong>Conclusions: </strong>The active chemicals in CEO can inhibit the cAMP/PKA/Grin2b pathway, reduce anxiety and depression, alleviate excitotoxicity caused by Glu synaptic overactivation, protect against hyp","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119423"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080217","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}
Yanqiang Qi , Yanyou Wang , Mingyue Ni , Yingxi He , Le Li , Yanli Hu
{"title":"Safflower yellow alleviates cognitive impairment in mice by modulating cholinergic system function, oxidative stress, and CREB/BDNF/TrkB signaling pathway","authors":"Yanqiang Qi , Yanyou Wang , Mingyue Ni , Yingxi He , Le Li , Yanli Hu","doi":"10.1016/j.jep.2024.118986","DOIUrl":"10.1016/j.jep.2024.118986","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Carthamus tinctorius L. (Safflower) was believed to have multiple benefits, including antioxidant effects, enhanced learning and memory, and improving neuronal injury. Safflower Yellow(SY) are the main active ingredients of Safflower, displays strong pharmacological potential treatment of Alzheimer's disease(AD). However, its effect on memory impairments remains insufficiently investigated.</div></div><div><h3>Aim of the study</h3><div>The study aims to investigate the effects of SY on cognitive functions in memory impairments model and to explore the mechanism of its action.</div></div><div><h3>Materials and methods</h3><div>We utilized the Morris Water Maze, Step-Through Test, Step-Down Test to assess the potential of SY in ameliorating learning and memory dysfunction caused by SCOP, NaNO<sub>2</sub> and ethanol in mice. Bioinformatic analysis and molecular biological approaches were used to study the related mechanisms of SY on anti-memory impairments.</div></div><div><h3>Results</h3><div>The results of the Morris Water Test suggested that SY could shorten the escape latency and the time of the first crossing platform in the mice with memory acquisition and memory consolidation impairments, and increase the platform crossing times. The results of the Step-Though test and Step-Down test showed that the escape latency in the mice was prolonged and the number of errors was reduced after SY treatment. ELISA experiments indicated that SY decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress markers (SOD, MDA, and GSH-PX) in scopolamine-induced mice. Western Blot and Nissl staining showed that SY could activated BDNF/TrkB/CREB signaling pathway and reduced neuronal damage.</div></div><div><h3>Conclusion</h3><div>The findings present that SY can restore the function of the cholinergic system, inhibit oxidative stress, regulate the expression of upstream and downstream proteins in the CREB/BDNF/TrkB pathway, and alleviate brain tissue damage to improve memory impairment in mice.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 118986"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501570","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}
Fangming Wang , Minli Liu , Qian Tang , Haijian Sun , Guangxia Yang , Jian Sun
{"title":"Anti-rheumatic arthritis efficacy of Pueraria montana extract against type-II collagen-induced rheumatoid arthritis rat model an in vitro and in vivo assessment","authors":"Fangming Wang , Minli Liu , Qian Tang , Haijian Sun , Guangxia Yang , Jian Sun","doi":"10.1016/j.jep.2024.119175","DOIUrl":"10.1016/j.jep.2024.119175","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Pueraria montana</em> (PM) is a Chinese medicinal herb used to treat alcoholism, inflammation, swelling, and anti-apoptosis. However, the mechanisms and active compounds of PM remain poorly understood.</div></div><div><h3>Aim of the study</h3><div>Chronic inflammatory diseases such as rheumatoid arthritis (RA) can affect multiple joints. Inflammation begins in the synovium and spreads to the surrounding cartilage and bone if left untreated. This study assessed the probable anti-arthritic mechanisms of action of PM extracts. Type II collagen emulsion-induced rheumatoid used as an <em>in vivo</em> model.</div></div><div><h3>Materials and methods</h3><div>TNF-α-stimulated MC cells were used to investigate the mechanism of PM extract in RA, and the PM extract was confirmed using HPLC analysis. The antiproliferative efficacy of PM was assessed by MTT assay, and apoptotic activity was evaluated using Hoechst staining and flow cytometry assessment. Furthermore, the matrix metalloproteinase (MMP) ratio and mRNA expression of Bcl-2, Cas-3, Cas-9, and SOCS1 were determined using ELISA and qRT-PCR.</div></div><div><h3>Results</h3><div>PM extract treatment possesses anti-arthritic properties in CIA rats and can suppress inflammation and inhibit the invasion and migration of MH7A cells. The upregulation of Bcl-2, a recognized inhibitor of apoptotic genes, prevents the release of cyto-C into the cytoplasm. The <em>in vivo</em> outcomes showed that PM reduced the arthritis score and toe swelling in CIA rats. In vitro, PM extract exhibited substantial antiproliferative and pro-apoptotic properties on TNF-α-induced MH7A cell lines. The invasive and adhesive properties of MH7A cells decreased, and MMP secretion was reduced.</div></div><div><h3>Conclusion</h3><div>This study suggests that the PM extract possesses anti-arthritic properties in the CIA model and is an extension of the clinical treatment of rheumatic arthritis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119175"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768106","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}