Journal of ethnopharmacology最新文献

{"title":"Study on the embryotoxic effects and potential mechanisms of Aconitum diterpenoid alkaloids in rat whole embryo culture through morphological and transcriptomic analysis.","authors":"Qiyi Feng, Jue Li, Chunxiu Xiao, Zhifan Wang, Xiaojie Li, Liang Xiong, Cheng Peng, Zhaoyan Chen, Fangyuan Tian, Jingyao Chen, Jiecheng Ji, Xiuli Zheng, Kai Xiao","doi":"10.1016/j.jep.2024.119198","DOIUrl":"10.1016/j.jep.2024.119198","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The lateral root of Aconitum carmichaelii Debeaux, or Fuzi, is recognized in Asia for its anti-inflammatory, analgesic, and cardiotonic effects. Its main active compounds are diester diterpenoid alkaloids (DDAs) such as aconitine (AC), mesoacitine (MA), and hypoaconitine (HA), which are also toxic and have a narrow therapeutic window, limiting their clinical use. Although Aconitum DDAs are known for cardiotoxic and neurotoxic effects, their impact on embryonic development remains unclear.</p><p><strong>Aim of the study: </strong>The embryotoxicity of three representative Aconitum DDAs (AC, MA, and HA) and their metabolites were systematically assessed, and the mechanisms underlying AC-induced embryotoxicity was explored.</p><p><strong>Materials and methods: </strong>The embryotoxicity of these DDAs was assessed by indicators such as morphological scores in a whole embryo culture (WEC) system. Immunofluorescence analysis was conducted to detect DNA damage and apoptosis in embryos, and transcriptomic analysis and western blotting were performed to explore the underlying mechanisms.</p><p><strong>Results: </strong>DDAs, particularly AC, induced dose-dependent developmental retardation and malformation in rat embryos. Notably, the embryotoxicity of AC metabolites such as benzoyltrypine (BAC) and aconine, was significantly reduced. AC treatment caused substantial DNA damage and apoptosis in embryos. Transcriptomic analysis indicate that AC treatment may impair DNA replication and histone synthesis by activating the p53/p21/CDK2/NPAT pathway, ultimately affecting embryonic development.</p><p><strong>Conclusion: </strong>Among these Aconitum DDAs, AC exhibited the strongest embryotoxicity, mainly through DNA damage and regulation of histone genes via the p53/p21/CDK2/NPAT pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119198"},"PeriodicalIF":4.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780213","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":"Mechanistic study of the regulation of mitochondrial function by the GPNMB/Nrf2/NF-κB signaling pathway mediated by Quzhi Tang to alleviate chondrocyte senescence.","authors":"Lishi Jie, Chaofeng Zhang, Yujiang Liu, Zeling Huang, Bo Xu, Zaishi Zhu, Yuwei Li, Peimin Wang, Xiaoqing Shi","doi":"10.1016/j.jep.2024.119165","DOIUrl":"10.1016/j.jep.2024.119165","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Quzhi Tang (QZT) is a compound formula consisting of six traditional Chinese medicinal herbs. It has achieved good clinical results in the treatment of knee osteoarthritis (KOA), and the potential drug mechanisms involved are worth exploring in depth.</p><p><strong>Materials and methods: </strong>Using single-cell transcriptome analysis, this study identified the key target of senescence, GPNMB. Then, it investigated the mechanism by which QZT regulates the GPNMB/Nrf2/NF-κB signaling pathway to repair mitochondrial damage and ameliorate the process of chondrocyte senescence.</p><p><strong>Results: </strong>We collected cartilage tissues from mice and identified GPNMB as a key target of chondrocyte senescence by combining transcriptomics, histopathology, molecular biology, and immunology methods. The effects of QZT on the level of chondrocyte senescence in mice and its ameliorative effect on KOA were studied. In in vivo experiments, we explored the mechanism of GPNMB in the development of senescence in detail and revealed that, after siRNA-GPNMB interference, chondrocytes exhibited reduced impairment of mitochondrial function and senescence under equal amounts of stimuli, increasing Nrf2 expression and reducing NF-κB expression. In addition, the level of oxidative stress increased in chondrocytes overexpressing GPNMB after lentiviral infiltration, aggravating the impairment of mitochondrial function. After treatment with QZT, chondrocytes overexpressing GPNMB were able to increase Nrf2 expression, decrease NF-κB expression, repair mitochondrial damage, and improve the degree of chondrocyte aging.</p><p><strong>Conclusion: </strong>We concluded that the GPNMB/Nrf2/NF-κB signaling pathway plays an important role in chondrocyte senescence and that QZT was able to reduce intracellular oxidative stress and restore impaired mitochondrial function by regulating the expression level of the GPNMB/Nrf2/NF-κB signaling pathway, reducing the level of chondrocyte senescence in the KOA process.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119165"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769294","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":"Tanshinone IIA, a component of Salvia miltiorrhiza Bunge, attenuated sepsis-induced liver injury via the SIRT1/Sestrin2/HO-1 signaling pathway.","authors":"Wencong Tian, Peng Song, Junhao Zang, Jia Zhao, Yanhong Liu, Chuntao Wang, Hong Fang, Hongzhi Wang, Yongjie Zhao, Xingqiang Liu, Yang Gao, Lei Cao","doi":"10.1016/j.jep.2024.119169","DOIUrl":"10.1016/j.jep.2024.119169","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>As a traditional Chinese medicine, Salvia miltiorrhiza Bunge has been widely used to treat ischemic and inflammation-related diseases for more than 2000 years. S. miltiorrhiza Bunge has hepatoprotective effects, but the underlying mechanism is not fully understood.</p><p><strong>Objective: </strong>To verify the effect of tanshinone IIA (Tan IIA), the main fat-soluble component of S. miltiorrhiza Bunge, on liver damage induced by sepsis/LPS-induced inflammation and further explore the underlying mechanisms.</p><p><strong>Materials and methods: </strong>Mice were administered Tan IIA 2 h before cecal ligation and puncture (CLP). Liver damage was evaluated by hematoxylin-eosin staining and changes in related serum factor levels. The expression of silent information regulator sirtuin 1 (SIRT1), Sestrin2, HO-1 and inflammatory cytokines was examined by immunohistochemistry or western blotting. LPS was used to induce the inflammatory response in vitro, and the activity of the related signaling pathway in response to Tan IIA was detected by western blotting. The SIRT1 inhibitor EX-527 and small interfering RNAs (siRNAs) were employed to determine the key roles of SIRT1 and Sestrin2 in Tan IIA's function.</p><p><strong>Results: </strong>We found that Tan IIA significantly improved the pathological changes and function of the liver, and alleviated liver damage in CLP mice. Additionally, SIRT1, Sestrin2, and HO-1 expression was significantly elevated after Tan IIA treatment compared with that in the CLP group both in vivo and in vitro, and Tan IIA treatment additionally suppressed pro-inflammatory cytokine release. However, inhibition of either SIRT1 or Sestrin2 remarkably abrogated the protective effects of Tan IIA. Most importantly, Sestrin2 appeared to function downstream of SIRT1 based on their expression changes after EX-527 or siRNA treatment.</p><p><strong>Conclusion: </strong>Tan IIA inhibited sepsis/LPS-induced inflammation through the SIRT1/Sestrin2/HO-1 pathway, thereby protecting against sepsis-induced liver injury (SLI). This study suggests that Tan IIA has therapeutic potential against SLI and that the SIRT1/Sestrin2/HO-1 signaling pathway might be a viable target for SLI treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119169"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769323","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 aqueous extract of Armadillidium vulgare Latreille alleviates neuropathic pain via inhibiting neuron-astrocyte crosstalk mediated by the IL-12-IFN-γ-IFNGR-CXCL10 pathway.","authors":"Yujie Yang, Shen Zhang, Jin Yang, Changheng Yao, Xue Li, Wenling Dai, Jihua Liu","doi":"10.1016/j.jep.2024.119173","DOIUrl":"10.1016/j.jep.2024.119173","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Armadillidium vulgare Latreille (AV), the dried body of pillbug, was originally described in Shennong's Classic of Materia Medica. As a common analgesic in animal-based traditional Chinese medicine, it is mainly used to relieve pain, promoting diuresis, relieving fatigue and so on. Our work demonstrated that AV could alleviate various types of acute and chronic pain including neuropathic pain (NP). And transcriptome sequencing analysis revealed that AV could suppress CXCL10 to alleviate NP, however, the upstream mechanisms governing CXCL10 synthesis remain vague.</p><p><strong>Aim of the study: </strong>The research's goal was to identify the mechanism via which AV regulates CXCL10 to ameliorate NP.</p><p><strong>Materials and methods: </strong>Chronic constriction injury (CCI) to the sciatic nerve was used to induce the NP model 14 days following surgery. To identify cell signaling pathways, various approaches were used, including transcriptome sequencing, western blotting, immunofluorescence, as well as ELISA. The in vitro assay involved the cultivation of neuron PC12 cells and astrocyte C6 cells.</p><p><strong>Results: </strong>Both in vivo and in vitro results demonstrated that IL-12/IL-18 enhanced IFN-γ production in spinal neurons, which acted on IFN-γ receptors on neurons and astrocytes to upregulate CXCL10 expression in these cells, illustrating the pivotal role of IL-12 in the crosstalk between neurons and astrocytes. The role of IL-12 in pain regulation was elucidated for the first time within the nervous system. Additionally, its synergistic interaction with IL-18 on the downstream IFN-γ-CXCL10 pathway dramatically altered the activation of neurons and astrocytes. And AV could suppress CXCL10 to alleviate NP by mediating the IL-12-IFN-γ-IFNGR signaling pathway.</p><p><strong>Conclusions: </strong>We explored a new target for NP by regulating neuron-astrocyte crosstalk and provided a theoretical basis for AV in clinical use.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119173"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769327","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":"Elemene mitigates oxidative stress and neuronal apoptosis induced by cerebral ischemia-reperfusion injury through the regulation of glutathione metabolism.","authors":"Pu Wu, Long-Hui Cheng, Yan-Lei Liu, Jiu-Long Zhang, Xue-Man Dong, Lin Chen, Yu-Xin Xu, Ying-Ying Ren, Hua-Min Zhang, Zhao-Qian Liu, Jian-Liang Zhou, Tian Xie","doi":"10.1016/j.jep.2024.119166","DOIUrl":"10.1016/j.jep.2024.119166","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Chinese materia medica (CMM) has a long history and extensive experience in treating ischemic stroke. Wen Ezhu, the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling, is renowned for promoting blood circulation, dispersing blood stasis, alleviating pain, and eliminating masses. Promoting blood circulation and removing blood stasis are essential principles in Traditional Chinese Medicine for treating stroke. Consequently, Wen Ezhu is frequently used in clinical practice as a key CMM for treating stroke. The Elemene active fraction (ELE), a sesquiterpene compound extracted from Wen Ezhu, primarily consists of β-Elemene. It also contains β-Caryophyllene, γ-Elemene, and δ-Elemene isomers. ELE has shown potential pharmacological effects in various diseases, including ischemic stroke. However, its precise mechanism of action in treating stroke remains to be confirmed.</p><p><strong>Aim of the study: </strong>To explore the therapeutic potential of ELE in acute ischemic stroke and elucidate its underlying mechanisms.</p><p><strong>Materials and methods: </strong>A rat model of middle cerebral artery occlusion reperfusion (MCAO/R) was used to evaluate ELE's effects. Therapeutic efficacy was assessed through mNSS scoring, magnetic resonance imaging (MRI), tetrazolium chloride (TTC) staining, Hematoxylin and eosin (H&E), and Nissl staining. Non-targeted metabolomics identified key pathways, confirmed using biochemical analysis, immunohistochemistry, and Western blotting. ROS levels and apoptosis-related proteins were also evaluated.</p><p><strong>Results: </strong>Our findings show that ELE administration significantly reduced the cerebral infarct area and lowered modified neurological severity scores (mNSS) in animals, indicating a strong neuroprotective effect. Metabolomics results highlight the glutathione (GSH) metabolic pathway as a key mechanism through which ELE exerts its therapeutic effects. Specifically, ELE upregulates glutathione reductase (GR) protein expression and downregulates glutathione peroxidase (GPX) expression. The regulatory process of ELE decreases oxidized glutathione (GSSG) levels and increases GSH levels, effectively reducing oxidative stress damage (lower reactive oxygen species levels) during CI/RI. This results in the downregulation of the pro-apoptotic protein Bax and the upregulation of the pro-survival protein Bcl-2, thus reducing neuronal apoptosis.</p><p><strong>Conclusions: </strong>ELE protects neurons in MCAO/R rats through the GSH metabolism pathway, balancing GSH and GSSG levels to mitigate oxidative stress and enhance neuroprotection in cerebral ischemia/reperfusion injury.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119166"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769282","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":"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":"<p><strong>Ethnopharmacological relevance: </strong>Quanduzhong capsule (QDZ), derived from Eucommia ulmoides 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.</p><p><strong>Aim of the study: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119176"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","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}

{"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":"<p><strong>Ethnopharmacological relevance: </strong>Pueraria montana (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.</p><p><strong>Aim of the study: </strong>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 in vivo model.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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 in vivo 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119175"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","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}

{"title":"Serum metabolomics and 16S rRNA amplicon sequencing reveal the role of puerarin in alleviating bone loss aggravated by antidiabetic agent pioglitazone in type 2 diabetic mice.","authors":"Junzheng Yang, Chuyi Chen, Hua Zhang, Baihao Chen, Ke Xiao, Yiming Tang, Kai Meng, Ling Qin, Peng Chen","doi":"10.1016/j.jep.2024.119128","DOIUrl":"10.1016/j.jep.2024.119128","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Pioglitazone (PIO) was an anti type 2 diabetes (T2D) agent but caused bone loss and bone marrow fat accumulation. Puerarin (PUE) was a natural component of herbal medicine extracted from Pueraria lobata (Willd.) Ohwi and reduced glycemia and improved bone mass as a supplementary drug. A combination of PIO and PUE might be good for maintaining bone mass and blood glucose.</p><p><strong>Aim of the study: </strong>We aimed to elucidate the potential correlation and underlying mechanisms of dietary supplement PUE in reducing side effects caused by PIO.</p><p><strong>Materials and methods: </strong>In vitro, alkaline phosphatase (ALP) staining, alizarin S (ARS) staining and qRT-PCR were performed to detect the osteogenesis activity in MC3T3-E1 cells. In vivo, we established the T2D model by treating C57BL6/J mice with high-fat diets and streptozotocin (STZ). Micro-CT, hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAcP) staining were performed to observe the difference in skeletal phenotype. Serum metabolomics and 16S rRNA amplicon sequencing were applied to analyze the potential effect of the combination of PIO and PUE.</p><p><strong>Results: </strong>We showed that the PUE could increase ALP activity and mineralization nodes of MC3T3-E1 with PIO. PIO could aggravate bone loss but PUE alleviated the effect caused by PIO in T2D mice. PUE promoted alpha-linolenic acid metabolism and glycerophospholipid metabolism, and affected the alpha diversity of the gut microbiome by regulating the genera of Alloprevotella, Fusobacterium, Rodentibacter, etc. Correlation analysis indicated that sphingosine-1-phosphate, nonadecylic acid, and margaric acid were associated with the effect of PUE.</p><p><strong>Conclusions: </strong>Taken together, we demonstrated that PIO combined with PUE was able to lower blood sugar levels without causing bone loss. The effect of PUE mainly correlated with the genua of Alloprevotella, Fusobacterium, Rodentibacter, and Alistipes. Also, alpha-linolenic acid metabolism and glycerophospholipid metabolism were major targets of PUE.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119128"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769295","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":"Shanyao regulates the PI3K/AKT/P21 pathway to promote oogonial stem cell proliferation and stemness restoration to alleviate premature ovarian insufficiency.","authors":"Yuxin Zou, Zuang Li, Yuewei Lin, Yunling Zheng, Ziyan Liu, Yucheng Li, Liuqian Huang, Zhuoting Chen, Ling Zhu","doi":"10.1016/j.jep.2024.119168","DOIUrl":"10.1016/j.jep.2024.119168","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Shanyao (SY, yam, Rhizoma Dioscoreae, the dried rhizome of Dioscorea oppositifolia L.) was recorded in the Chinese pharmacopoeia and was often used in the treatment of premature ovarian insufficiency (POI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of study: &lt;/strong&gt;To evaluate the efficacy of shanyao in cyclophosphamide (CTX)-induced POI and explore its potential mechanism of action.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;We employed network pharmacology, Liquid Chromatograph Mass Spectrometer (LC-MS), and molecular docking methods to identify active compounds and core targets, and predict the mechanism of shanyao for treating POI. The mechanism was subsequently validated through a series of experiments. Female Sprague-Dawley (SD) rats were randomly divided into five groups: control (CON), model, estradiol valerate (EV), low-dose shanyao, and high-dose shanyao. An experimental rat model of POI was established using cyclophosphamide and treated with either shanyao or EV for a duration of two months. We assessed the efficacy of shanyao in vivo through methods such as weighing, Enzyme-linked Immunosorbent Assay (ELISA), and Hematoxylin and Eosin (H&E) staining. Oogonial stem cells (OSCs) were isolated, after modeling, treated them with a serum containing either shanyao or EV. Using methods such as CCK8 assay, immunofluorescence staining, flow cytometry (FCM) analysis, and Western blot analysis to verify the mechanism of shanyao in treating POI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this study, we found that after treatment with shanyao, the general condition of POI rats was improved, body weight and the ratio of ovarian weight to body weight were increased, FSH, E2 and AMH levels were improved, primary follicles and preantral follicles were significantly increased, atretic follicles were decreased. However, the number of antral follicles and fresh corpus luteum was no statistical difference. We identified 10 active compounds of shanyao that act on 220 target genes, 176 of which are associated with POI. Denudatin B and Kadsurenone were finally identified as core components. Through topological analysis, 18 key targets were selected, and ultimately PI3K, CCND1, and CDK4 were identified as core targets. Molecular docking results showed that core components had good binding energy with core targets. The results of GO and KEGG enrichment analysis mainly focus on cell cycle regulation and PI3K/AKT signaling pathway. A series of molecular biology experiments confirmed that after shanyao treatment, the phosphorylation level of PI3K and AKT in POI rats were increased, P21 was inhibited, PI3K/AKT/P21 signaling pathway was activated, and the expression levels of CCND1 and CDK4 were increased. At the same time, the expression of Oct4, fragilis and Mvh of ovarian stem cells was up-regulated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The active compounds of shanyao can regulate the PI3K/AKT/P21 signaling pathway, promote the proliferatio","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119168"},"PeriodicalIF":4.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769301","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 potent bioactive compounds and anti-angiogenic pathways in Gekko swinhonis Guenther for gastric cancer therapy.","authors":"Yu Zheng, Chang Lu, Yong Jiang, Nina Wei, Chenqi Chang, Weidong Li, Linwei Chen, Rui Chen, Zhipeng Chen","doi":"10.1016/j.jep.2024.119156","DOIUrl":"10.1016/j.jep.2024.119156","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Gekko swinhonis Guenther, commonly referred to as Gecko in the following text, belongs to the genus Gekko within the family Gekko. Its dried whole body is a widely utilized traditional Chinese medicine, demonstrating significant efficacy in the treatment of gastrointestinal malignancies, particularly gastric cancer (GC). Nevertheless, the composition of the gecko is complex, necessitating further research into its active ingredients for the treatment of GC.</p><p><strong>Aim of the study: </strong>Isolation and characterization of the most active components in Gecko based on their anti-GC mechanisms of vascular endothelial cell inhibition and anti-neovascularization.</p><p><strong>Materials and methods: </strong>We utilized the enzymatic hydrolysate of Geckos to investigate its effectiveness and underlying mechanisms. Initially, we assessed its efficacy in ectopic and in-situ GC tumor-bearing mouse models. Subsequently, we evaluated the effectiveness of peptides, aliphatics, and small molecules derived from Gecko using CCK-8 and 3D tumor spheroid assays. The activities of peptides S1-S4 were further examined through these experiments. Finally, we screened, synthesized, and investigated five potential peptides for their pharmacodynamics in the CCK-8 assay and in the in-situ GC model mice.</p><p><strong>Results: </strong>The Gecko can inhibit the formation of blood vessels in the tumor microenvironment, providing a localized treatment for GC. The peptide components significantly inhibit vascular endothelial cells and impede the formation of new blood vessels, with the S2 peptide sections (0.3 KD - 3 KD) demonstrating the most potent inhibitory activity against angiogenesis. One of the active peptides effectively suppresses the growth of in-situ GC in nude mice through angiogenesis inhibition and also modulates immunity, all while exhibiting excellent biosafety.</p><p><strong>Conclusions: </strong>We have achieved a significant breakthrough in the local treatment of GC using Gecko. Through pharmacodynamic experiments and a systematic process of isolation and identification, we identified the most effective anti-GC ingredients of Gecko, based on their mechanisms of inhibiting vascular endothelial cells and promoting anti-angiogenesis. Furthermore, we synthesized a lead peptide that demonstrates promising therapeutic efficacy and safety.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119156"},"PeriodicalIF":4.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755019","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}