Journal of ethnopharmacology最新文献

{"title":"Danhong Injection Modulates Microglial Polarization and Neuroinflammation via the JUNB/NF-κB Pathway in Ischemic Stroke.","authors":"Meixia Xie, Huilin Huang, Yingxin Lu, Lei Chen, Shumei Wang, Minghua Xian","doi":"10.1016/j.jep.2024.119247","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119247","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ischemic stroke (IS) is a leading cause of death and disability in China. Danhong Injection (DHI) is a traditional Chinese medicine preparation made from Salvia miltiorrhiza var. miltiorrhiza and Carthamus tinctorius L. It is used for treating stroke in China with proven safety and efficacy. Microglia M1/M2 polarization is a key factor in IS inflammatory response. However, the key transcription factors that regulate microglia polarisation are unknown. It is also not clear how DHI exerts its mechanism in the treatment of IS.</p><p><strong>Aim of the study: </strong>This research aimed to investigate the effect of DHI on microglial polarization and neuroinflammation associated with IS and to elucidate the underlying mechanisms, with an emphasis on the JUNB/NF-κB signaling pathway.</p><p><strong>Materials and methods: </strong>An oxygen-glucose deprivation (OGD) damage cell model and a permanent middle cerebral artery occlusion (pMCAO) model in C57BL/6 mice were employed. Neurological deficits, cerebral infarct volume, and microglial activation were assessed. Non-targeted metabolomics analysis with UHPLC-QE-MS and molecular biology methods, including RT-qPCR and Western blot, were applied to investigate the mechanisms.</p><p><strong>Results: </strong>In vivo, DHI decreased inflammation, reduced brain damage, and enhanced neurological function. DHI also ameliorated microglial activation and OGD-induced apoptosis in vitro. Metabolomics analysis identified significant metabolic changes, particularly in amino acid metabolism. Additionally, DHI treatment decreased the upregulated mRNA levels of ASS1 and ASL after OGD, indicating an influence on the arginine biosynthesis pathway, which is crucial for microglial function. DHI modulated the M1 to M2 phenotypes of microglial polarization and regulated microglial polarization through the JUNB/NF-κB signaling pathway. This was confirmed by JUNB silencing experiments.</p><p><strong>Conclusions: </strong>DHI exhibits neuroprotective effects via suppressing ASS1 through the JUNB/NF-κB pathway, promoting the M2 state of microglia, and lowering the expression of inflammatory cytokines. This research unveils the potential therapeutic target of JUNB for IS treatment and sheds light on the novel intervention mechanism of DHI in microglial cells.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119247"},"PeriodicalIF":4.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854237","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":"Unveiling the potential and specificity of the Mahoran ethnopharmacopoeia: a field survey.","authors":"T A M-H U I Thibault, E V E N O Yannick, D I M A S S I Abassi, B E R T R A N D Cédric, H A D D A D Mohamed, C H A S S A G N E François","doi":"10.1016/j.jep.2024.119255","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119255","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>A significant portion of Mahoran people relies on traditional medicine to address their healthcare needs. However, very few studies have been carried out on this subject, and few data are available on the practices, plants used, and ailments most commonly treated by their traditional medicine.</p><p><strong>Aim of the study: </strong>Within this context, the aim of this study was to identify the diseases most commonly treated by traditional Mahoran medicine, as well as the plants most commonly used against these various ailments.</p><p><strong>Materials and methods: </strong>From January to April 2023, a semi-structured survey was carried out in Mayotte island. A total of 103 participants were interviewed including 65 non specialists, 21 knowledgeable, and 17 specialists. A thorough literature review was performed on the most cited plant species to evaluate the benefit-risk of each remedy.</p><p><strong>Results: </strong>Participants mentioned using 474 remedies (prepared mostly with herbal ingredients) to treat 65 diseases. These diseases belong to various health categories of which the most represented ones were digestive system, respiratory system, genital system, general, and muscular system. The two most common ailments cited by participants were stomachache (41/103) and cough (36/103). A total of 154 plant species were identified, with Coleus amboinicus, Citrus aurantiifolia, Moringa oleifera, and Ocimum gratissimum being the main plants reported. Massage therapy was the second most important traditional practices reported after the use of herbal remedies.</p><p><strong>Conclusion: </strong>Our survey confirms the importance of traditional medical pratices in Mayotte island. The following plants: Aerva lanata, Cardiospermum halicacabum, Coleus madagascariensis Paullinia pinnata, and Woodfordia fruticosa stand out from the others in terms of their use and number of citations, and it would be interesting to study their pharmacological and toxicological properties. Traditional medicine in Mayotte also possesses specificities, notably with the use of particular ingredients such as salt, coral stone, or even white clay. Furthermore, throughout the study, we noticed that chronic diseases such as diabetes or hypertension were extensively treated. This could be linked to the fact that the prevalence of these diseases is quite high on the island.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119255"},"PeriodicalIF":4.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854256","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":"Anti-sepsis effects of Dahuang Mudan decoction and its disassembled prescriptions.","authors":"Ren-Yi Lu, Zhong-Yi Ling, Lin-Lin Chen, Wei-Heng Xu, Xin-Hao Xing, Ze-Cheng Song, Li Chen, Yan Wang","doi":"10.1016/j.jep.2024.119248","DOIUrl":"10.1016/j.jep.2024.119248","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Dahuang Mudan decoction (DMD) is a traditional Chinese prescription from Zhang Zhongjing's Synopsis of the Golden Chamber. In clinical practice, it is often used in the treatment of infectious diseases.</p><p><strong>Aim of the study: </strong>To assess the therapeutic effect of DMD and its disassembled prescriptions on septic mice, and explore its potential mechanism.</p><p><strong>Materials and methods: </strong>Cecal ligation and puncture (CLP) sepsis and endotoxemia mice models were established. The effects of DMD, its disassembled prescriptions and active compounds were studied. Xuebijing injection (XBJ) was used as positive drug. Mice 7-day survival rates, blood biochemical markers, hematoxylin and eosin (HE) staining and immune cell infiltration were used to evaluate the overall protective effect of the drugs on mice. Inflammatory cytokines and coagulation activation indicators were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>DMD, its Huoxue prescription, constituent drugs Mudanpi (MDP) and Taoren (TR) significantly protected mice with sepsis, improved the survival rate, reduced the degree of organ damage, and reduced the infiltration of immune cells in the lung tissues. The protective effect is comparable to that of XBJ. MDP and TR inhibited the levels of inflammatory factors and coagulation activation in septic mice. Paeonol and paeoniflorin in MDP showed significant protective effects on septic mice, and inhibited inflammatory cytokines level and coagulation activation.</p><p><strong>Conclusion: </strong>These results confirm that DMD and its disassembled prescriptions have good therapeutic effect on septic mice, and the mechanism may be related to inhibition of the inflammatory response and coagulation activation.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119248"},"PeriodicalIF":4.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buyang huanwu decoction inhibits the activation of the RhoA/Rock2 signaling pathway through the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis following cerebral ischemia-reperfusion injury.","authors":"Yanling Li, Zhongji Hu, Linli Xie, Tingting Xiong, Yanyan Zhang, Yang Bai, Huang Ding, Xiaoping Huang, Xiaodan Liu, Changqing Deng","doi":"10.1016/j.jep.2024.119246","DOIUrl":"10.1016/j.jep.2024.119246","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Buyang Huanwu Decoction (BYHWD) exerts its anti-cerebral ischemia effects through multiple pathways and targets, although its specific mechanisms remain unclear.</p><p><strong>Aim of the study: </strong>Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) metabolomics and other methods were employed to investigate the role of BYHWD in inhibiting neuronal apoptosis following cerebral ischemia-reperfusion by modulating the RhoA/Rock2 pathway.</p><p><strong>Methods: </strong>A rat model of exhaustion swimming combined with middle cerebral artery occlusion (ES + I/R) was established to evaluate the intervention effects of Buyang Huanwu Decoction on cerebral ischemia-reperfusion. This was assessed using neurological function scores, Qi deficiency and blood stasis syndrome scores, HE staining, Nissl staining and TT staining. Differential metabolites and metabolic pathways associated with cerebral ischemia-reperfusion were identified using UPLC-QTOF-MS metabolomics, with key differential metabolites validated through ELISA. Molecular docking techniques were employed to predict interactions between the key differential metabolite, hippuric acid, and its primary downstream pathways. Finally, the levels of neurocellular apoptosis, as well as key molecules in the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway, were measured.</p><p><strong>Results: </strong>The results indicated that the primary differential metabolites associated with BYHWD's protective effects against ischemia-reperfusion injury were hippuric acid, lysophosphatidic acid, and lysophosphatidylethanolamine, with the main metabolic pathway being phenylalanine metabolism. Molecular docking studies demonstrated that malonic acid exhibited a strong affinity for proteins related to the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway.Furthermore, we found that BYHWD treatment significantly decreased the apoptosis rate of cells following cerebral ischemia-reperfusion and inhibited the expression of key molecules in both the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway in brain tissue.</p><p><strong>Conclusion: </strong>BYHWD ameliorated brain tissue injury after cerebral ischemia/reperfusion in rats with qi deficiency and blood stasis. The underlying mechanism may involve BYHWD's inhibition of the RhoA/Rock2 signaling pathway activation through modulation of the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis mediated by the mitochondrial apoptosis pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119246"},"PeriodicalIF":4.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837049","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":"Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.","authors":"Kun Wang, Mengmeng Shen, Hongguang Tang, Jidong Zhou, Yan Liu, Dejun Niu, Zhen Zeng, Lihong Pan, Jingchun Yao, Chenghong Sun","doi":"10.1016/j.jep.2024.119241","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119241","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Chronic fatigue syndrome (CFS), as a complex, multisystemic, and multisystemic disorder affecting multiple organs and systems, often accompanies by symptoms such as post-exercise discomfort, sleep disorders, cognitive difficulties, and orthostatic intolerance. Jingfang Granule (JFG) is a traditional Chinese medicine that have significant protective effects on CFS, but the mechanism is still vague.</p><p><strong>Aim of study: </strong>This study was designed to evaluate the protective mechanism of JFG on mice with CFS.</p><p><strong>Materials and methods: </strong>The combined stimuli method was used to establish the mice CFS model, and JFG was orally administered. The body weight, exhaustion swimming training and tail suspension test were assayed every 7 days to evaluate the improvement of JFG on CFS. Lactic acid, adenosine triphosphate (ATP), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), IL-1β, TNF-α, IL-6 in serum and liver glycogen, muscle glycogen in muscle were analyzed. Transmission electron microscopy was used to detect mitochondrial morphology. The regulatory networks were investigated by proteomics and central carbon metabolomics, which were verified by western blot.</p><p><strong>Results: </strong>JFG reversed the loss of weight and reduce of exhaust swimming time (P < 0.05) induced by CFS in mice, and increased the tail suspension time (P < 0.05), indicating that JFG has an improving effect on CFS. Meanwhile, JFG increased the spleen index (P < 0.05), decreased the thymus index (P < 0.05) and cardiac index (P < 0.05), inhibited the secretion of Lactic acid (P < 0.05), and increased the content of liver glycogen (P < 0.05), muscle glycogen (P < 0.05), and ATP (P < 0.05), and improved mitochondrial morphology in mice with CFS. JFG also inhibited the release of TNF-α (P < 0.05), IL-1β (P < 0.05) and IL-6 (P < 0.05) in serum by inhibiting TLR4/NF-κB signaling pathway and NLRP3 inflammasome signaling pathway, and inhibited oxidative stress by activating Nrf2/HO-1/NQO1 axis. Integrated central carbon metabolomics, proteomics and western blot showed that JFG intervened in CFS by increasing the expression of Idh1 (P < 0.05) and Idh2 (P < 0.01) to promote tricarboxylic acid (TCA) cycle.</p><p><strong>Conclusions: </strong>This study confirmed that JFG promoted the TCA cycle by increasing the expression of Idh1 and Idh2, and then inhibited inflammation and oxidative stress to prevent CFS injury, which provided a potential drug candidate for CFS treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119241"},"PeriodicalIF":4.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846705","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":"Cordycepin Extracted from Cordyceps militaris mitigated CUMS-induced depression of rats via targeting GSK3β/β-catenin signaling pathway.","authors":"Yupeng Wang, Yanhui Deng, Mingmei Feng, Jiaxi Chen, Mengling Zhong, Zhipeng Han, Qi Zhang, Yang Sun","doi":"10.1016/j.jep.2024.119249","DOIUrl":"10.1016/j.jep.2024.119249","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Cordycepin, the main active component of Cordyceps militaris, exhibits various pharmacological activities, including anti-tumor and antioxidant effects. However, its antidepressant effect and the underlying mechanisms remain unclear.</p><p><strong>Aim of review: </strong>This study aimed to explore the antidepressant effect of cordycepin and elucidate the potential molecular mechanisms.</p><p><strong>Materials and methods: </strong>Chronic unpredictable mild stress (CUMS) rat model was established to assess antidepressant effect of cordycepin. Gas chromatography-mass spectrometry (GC-MS) metabolomics with integrated network pharmacology were used to find differential metabolites in serum, brain, and cerebrospinal fluid of rats and identify potential target by cordycepin. Western blot and Real-time PCR were applied to validate the signaling pathway.</p><p><strong>Results: </strong>Cordycepin alleviated CUMS-induced depression-like behaviors by weight gain, sucrose preference increment, immobility time reduction, total travelling distance extension and serum corticosterone levels reduction. Metabolomics showed that cordycepin reversed CUMS-induced metabolic disturbances through alanine and TCA cycle metabolism pathways. Network pharmacology identified GSK3β as a potential target. Cordycepin increased protein levels of p-GSK3β, β-catenin and nuclear β-catenin, and enhanced transcription of downstream genes PKM, LDHA, Cyclin D1 and C-myc in brains of CUMS-induced rats.</p><p><strong>Conclusions: </strong>This study indicated that cordycepin exerted antidepressant effect by modulating GSK3β/β-catenin pathway, suggesting its potential as a candidate agent for depression.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119249"},"PeriodicalIF":4.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846693","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":"Panax Quinquefolium Saponins protects neuronal activity by promoting mitophagy in both in vitro and in vivo models of Alzheimer's disease.","authors":"Wei Zhao, Rui Yang, Xin Meng, Shi-Qi Xu, Meng-Meng Li, Zhi-Chao Hao, Si-Yi Wang, Yi-Kai Jiang, Anam Naseem, Qing-Shan Chen, Li-Li Zhang, Hai-Xue Kuang, Bing-You Yang, Yan Liu","doi":"10.1016/j.jep.2024.119250","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119250","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>In the realm of traditional Chinese medicine, Panax quinquefolius L. has garnered significant attention for its potential to treat various ailments associated with deficiencies, including qi, blood, and kidneys. As its primary bioactive constituent, Panax quinquefolius saponins (PQS) have the potential therapeutic role of Alzheimer's disease (AD) treatment, but with unclear mechanisms of action. Meanwhile, AD is considered as a common dementia disease with kidney insufficiency and deficiency by traditional medicine, and often accompanied by autophagy in modern medical research.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the therapeutic effects of PQS on AD through the regulation of mitophagy.</p><p><strong>Materials and methods: </strong>The chemical constituents of PQS were characterised using the UPLC-QTOF-MS technique. After that, the HT22 cell line was used to establish the D-galactose-induced cell model, and the SAMP8 mice model of AD was also employed. Cell viability was assessed using the CCK-8 assay, ROS detection, JC-1 staining, Mito-tracker Red and LC3 staining, and Mito-tracker Green and Lyso-tracker Red staining were used to assess levels of mitophagy. The Morris Water Maze (MWM) was used for the experimental evaluation of learning and memory abilities in mice. Subsequently, the mechanism was studied by pathological staining and western blotting.</p><p><strong>Results: </strong>Fifty-eight triterpenoid saponins were identified from PQS, and PQS alleviated D-galactose-induced HT22 cell death and increased intracellular levels of mitochondrial autophagy-related factors. In vivo, PQS significantly improved cognitive deficits and mitigated AD-like pathological features by activating the mitophagy mechanism. Furthermore, PQS may promote Pink1/Parkin-mediated mitophagy by activating the AMPK/mTOR/ULK1/DRP1 and SIRT1/PGC-1α pathways.</p><p><strong>Conclusion: </strong>In conclusion, PQS have demonstrated the potential to mitigate mitochondrial dysfunction and enhance cognitive function in AD through the activation of mitophagy. This promising strategy holds great promise for the treatment of AD.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119250"},"PeriodicalIF":4.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837076","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":"The molecular mechanism of Xiaoyaosan in treating major depressive disorder: Integrated analysis of DNA methylation and RNA sequencing of the arcuate nucleus in rats.","authors":"Rongyanqi Wang, Tan Zou, Yidi Wang, Yueyun Liu, Xiaowei Mo, Yueyue Chen, Xiaojuan Li, Jiaxu Chen","doi":"10.1016/j.jep.2024.119234","DOIUrl":"10.1016/j.jep.2024.119234","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Xiaoyaosan, a classic Chinese herbal formula, exhibits promising antidepressant effects. However, its specific antidepressant mechanisms remain incompletely understood. Previous studies have highlighted the significant role of DNA methylation in the pathogenesis of major depressive disorder (MDD). Yet, whether the effects of Xiaoyaosan are linked to DNA methylation and its regulation remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This study aims to explore and verify the molecular mechanism of Xiaoyaosan in treating MDD via integrated analysis of DNA methylation and RNA sequencing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;In this study, a chronic unpredictable mild stress (CUMS) model was established to induce MDD in rats, which were subsequently orally treated with Xiaoyaosan, with fluoxetine as a positive control. Antidepressant effects were assessed by the open field test, sucrose preference test, and forced swimming test. Whole-genome bisulfite sequencing (WGBS) and bulk RNA sequencing were performed in the arcuate nucleus of hypothalamus to assess methylation changes and identify differentially expressed genes. Bioinformatics analyses were conducted to explore methylation alterations, RNA sequencing profiles, and their shared epigenetic as well as gene expression changes, to identify candidate genes. Finally, RT-PCR was used to validate the key differential genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Xiaoyaosan effectively reversed depressive-like behaviors. Further, Xiaoyaosan treatment involved multiple epigenetic modifications. The results of differentially methylated genes showed that there were 1353 overlapped genes between M-vs-C-hypo gene and X-vs-M-hyper gene, 5326 overlapped genes between M-vs-C-hyper gene and X-vs-M-hypo gene. GO and KEGG enrichment analyses indicated these intersecting genes were involved in biological regulation, transcription factors, appetite and endocrine control systems, etc. The analysis of differentially expressed genes from RNA sequencing revealed that there were 25 overlapping genes between the M vs C hypomethylated group and the X vs M hypermethylated group, while 81 overlapping genes were identified between the M vs C hypermethylated group and the X vs M hypomethylated group. Those differential genes regulated by methylation enriched in processes related to brain and neuronal growth, neuropeptide and hormone activation, as well as biological processes and molecular functions associated with protein translation, synthesis, transport, and localization. The integrated analysis of DNA methylation and RNA sequencing screened 14 potentially differential genes, which were associated with appetite regulation, energy metabolism, and neuroreceptor ligands. PCR verification found that Lmx1b, Abcc5, Gpc3 and Cfb showed statistical differences.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The antidepressant mechanism of Xiaoyaosan involves the biological regulati","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119234"},"PeriodicalIF":4.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828841","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":"Guilu Erxian Jiao remodels dendritic spine morphology through activation of the hippocampal TRPC6-CaMKIV-CREB signaling pathway and suppresses fear memory generalization in rats with post-traumatic stress disorder.","authors":"Yue Qu, Jingna Gu, Lanxin Li, Yuqi Yan, Can Yan, Tiange Zhang","doi":"10.1016/j.jep.2024.119252","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119252","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Guilu Erxian Jiao (GLEXJ) is a renowned traditional Chinese herbal formula used to tonify the kidney. It is employed to treat psychiatric disorders, and alleviate memory impairment, cognitive dysfunction, and behavioral disorders. Modern pharmacological studies have demonstrated GLEXJ's ability to significantly inhibit the fear response in post-traumatic stress disorder (PTSD) and facilitate the extinction of fear memory. However, the underlying pharmacological mechanisms remain elusive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;Fear memory generalization, a fundamental characteristic of PTSD, remains poorly understood, and optimal pharmacological treatments are lacking. This study aimed to investigate GLEXJ's inhibitory effects on fear memory generalization in PTSD rats and elucidate its underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;PTSD rats were induced using the single prolonged stress and electrical stimulation (SPS&S) protocol and treated with GLEXJ or paroxetine (PRX). Fear memory generalization was assessed using a contextual fear memory test. Hippocampal dendritic spine morphology was analyzed using Golgi-Cox staining. The chemical composition of GLEXJ was determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Network pharmacology was employed to predict GLEXJ's therapeutic mechanism in PTSD treatment. Western blotting and immunofluorescence were used to measure indicators of the transient receptor potential channel 6 (TRPC6)-mediated calcium/calmodulin-dependent protein kinase IV-cAMP response element-binding protein (CaMKIV-CREB) signaling pathway. In vitro, TRPC6 was suppressed in rat adrenal pheochromocytoma (PC12) cells using lentiviral vectors, and phalloidin staining was employed to examine changes in Fibros actin (F-actin), elucidating the mechanistic effects of GLEXJ-containing serum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GLEXJ significantly mitigated fear memory generalization in PTSD rats, even with repeated stress exposure. It also improved abnormal hippocampal dendritic spine morphology. Network pharmacology analysis confirmed that GLEXJ was closely related to the Ca&lt;sup&gt;2+&lt;/sup&gt; signaling pathway in PTSD treatment. PTSD rats exhibited disrupted TRPC6-mediated CaMKIV-CREB signaling and impaired synaptic plasticity. GLEXJ upregulated TRPC6 expression, reactivated the CaMKIV-CREB pathway, and promoted synaptic remodeling. In vitro studies confirmed that TRPC6 suppression reduced F-actin levels while GLEXJ-containing serum increased TRPC6 expression and F-actin content.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;GLEXJ activates CaMKIV-CREB signaling by upregulating TRPC6 in the hippocampus of PTSD rats, leading to improved dendritic spine dynamics and synaptic remodeling. This mechanism contributes to the attenuation of fear memory generalization. Given the limitations of current PTSD treatments, these findings offer pote","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119252"},"PeriodicalIF":4.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837069","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":"The dynamic distribution patterns and lung targeting efficiency in rats of 9 bioactive components in Siraitia grosvenorii.","authors":"GuangYu Chen, JuanJiang Wu, Huaxue Huang, Jianan Mao, Shuang Zhan, Zhi Peng, Dai Liu, Wang Wei","doi":"10.1016/j.jep.2024.119233","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119233","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Siraitia grosvenorii (S. grosvenorii) is a traditional herbal medicine employed for the prevention of lung diseases. Mogrosides and flavonoids are postulated to be the principal active components. Nevertheless, the dynamic distribution of its active components in vivo and the amount of accumulation in the lung target tissue remain indistinct.</p><p><strong>Aim of the study: </strong>This study investigates the dynamic distribution patterns of 9 bioactive components within the extract of S. grosvenorii in rat blood, heart, liver, spleen, lung, and kidney, along with its pulmonary targeting.</p><p><strong>Materials and methods: </strong>The blood, heart, liver, spleen, lung, and kidney samples of rats were obtained at diverse time points after oral administration of S. grosvenorii decotion, and a UPLC-MS/MS method was developed to determine the contents of 9 bioactive components (Siamenoside I, Grosvenorine, 11-O-Mogroside V, Mogroside II-E, Mogroside III-E, Mogroside IV-A, Mogroside V, Mogroside VI and Kaempferitrin) within the samples. The concentration-time curves of each component in each sample were plotted and the pharmacokinetic parameters were computed.</p><p><strong>Results: </strong>The AUC_0→∞ and C_max of 9 bioactive components in lung tissue were conspicuously higher than those in heart, liver, spleen, and kidney. For instance, the AUC_0→∞ of Mogroside V in lung tissue was 7.20 to 55.54 times higher than that in blood and other tissues, and the C_max in lung tissue was 3.315 to 96.70 times higher than that in blood and other tissues. The lung target efficiency of 9 bioactive components ranged from 1.885 to 15.80, indicating that the active components of S. grosvenorii exerting pharmacological effects are highly concentrated in the lung target tissue. The T_max of 9 bioactive components in blood was within the range of 10.20 to 100.2 min, while the T_max of the heart and liver was 20 min. The T_max of all the components in the lung was 50 min, while the T_max of the spleen and kidney was from 80 to 100 min, suggesting that 9 bioactive components entered the blood rapidly and then distributed to the heart and liver in large quantities, before entering the lung tissue in large quantities and eventually distributing to the spleen and kidney. The elimination half-life (T_1/2) of the majority of 9 bioactive components was less than 1 hour, and the MRT of most of them was less than 3 hours.</p><p><strong>Conclusions: </strong>S. grosvenorii is a naturally lung-targeted herbal medicine, and the clinical administration ought to be based on pharmacokinetic parameters such as Tmax, Cmax, AUC_0→∞, T_1/2, and MET_0→∞ in lung tissue for designing a precise, rigorous, and rational administration plan.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119233"},"PeriodicalIF":4.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828837","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}