Journal of ethnopharmacology最新文献

{"title":"Integrative pharmacological analysis of modified Zuojin formula: Inhibiting the HIF-1α-mediated glycolytic pathway in chronic atrophic gastritis","authors":"Shan Liu ,&nbsp;Tai Zhang ,&nbsp;Lihui Fang ,&nbsp;Lanshuo Hu ,&nbsp;Xiaolan Yin ,&nbsp;Xudong Tang","doi":"10.1016/j.jep.2024.119136","DOIUrl":"10.1016/j.jep.2024.119136","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zuojin formula (ZJF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for gastritis. Modified Zuojin formula (MZJF) was adapted based on traditional Chinese medicine (TCM) theories concerning gastric atrophy and dysplasia, along with extensive clinical experience, has been clinically employed to treat chronic atrophic gastritis (CAG). However, the underlying mechanisms by which MZJF intervenes in CAG remain to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to evaluate the effects of MZJF intervention in CAG and explore its potential mechanisms.</div></div><div><h3>Methods</h3><div>Four induction factors were used to establish a CAG rat model. HE and AB-PAS staining was utilized to assess the effects of MZJF in the intervention of CAG. The stomach weight index and gastric acid pH was used to assess the overall state of stomach. ELISA was used to assess the gastric mucosal inflammatory response. Using transmission electron microscopy to observe chief cells and parietal cells, we evaluated the improvement of ultrastructure by MZJF. Through network pharmacology analysis, the possible regulatory mechanism of MZJF in CAG was preliminarily explored. Binding interactions between MZJF components and predicted targets were explored using molecular docking. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot, biochemical analysis and TUNEL staining were applied to validate the effect of MZJF on predicted pathway.</div></div><div><h3>Results</h3><div>MZJF treatment ameliorated gastric mucosal pathology, inflammation, cellular ultrastructural damage and PG levels, halted the exacerbation of CAG in rats, along with a reduction in stomach weight index and gastric acid pH. A total of 79 compounds in MZJF targeting 203 CAG-related molecules were identified through network pharmacology. Enrichment analysis of the core targets was focused on the hypoxia inducible factor-1α (HIF-1α) signaling pathway. Molecular docking results identified HIF-1α as stable binding targets for MZJF primary components. Subsequently, PCR, WB, and biochemical results showed that MZJF suppressed the gene and protein expression levels of HIF-1α and its downstream molecules including glycolytic enzymes and transporters, modulated glucose, pyruvic acid and lactate levels in gastric mucosal tissue. Moreover, MZJF induced apoptosis of gastric epithelial cells, as evidenced by the upregulation of cleaved caspase-3, Bax, Bax/Bcl-2 and TUNEL positive cells ratio.</div></div><div><h3>Conclusions</h3><div>MZJF suppressed the HIF-1α-mediated glycolytic pathway, and promoted cell apoptosis, thereby halting the malignant transformation of CAG. The study provides a valuable reference point for applying TCM in preventing and treating CAG.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119136"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693041","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":"Deciphering mechanism of Buyang Huanwu Decoction in regulating macrophage polarization to alleviate atherosclerosis via virtual screening and experimental verification.","authors":"Qingping Xiong, Yuhan Zhang, Yisa Cai, Yong Zhu, Yi Jing, Heng Li, Guangzhen Zheng, Jie Chen, Shiyan Wang, Zhimeng Xu, Yadong Yu, Yingying Shi, Hui Yong, Xiangyang Cao","doi":"10.1016/j.jep.2024.119152","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119152","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Buyang Huanwu Decoction (BYHWD), a traditional prescription known for its Supplementing Qi and Promoting Blood Circulation, has demonstrated noteworthy therapeutic roles in regulating macrophage polarization to atherosclerosis (AS). However, its underlying mechanisms remain unknown.</p><p><strong>Aim of the study: </strong>The purpose of this paper was to decipher mechanism of BYHWD in regulating macrophage polarization to alleviate AS.</p><p><strong>Materials and methods: </strong>A comprehensive virtual screening strategy, incorporating network pharmacology and batch molecular docking, combined with experimental validation techniques, was employed to systematically elucidate the underlying mechanism of BYHWD regulating macrophage polarization to alleviate AS.</p><p><strong>Results: </strong>Firstly, based on high-fat diet induced AS model in apolipoprotein E-deficient mice, it was found that BYHWD can significantly regulate macrophage polarization to alleviate AS. Then, the network pharmacological analysis revealed that the core targets of BYHWD regulating macrophage polarization to alleviate AS mainly involved TP53, AKT1 and BCL2. The mitochondrial function and metabolism were the main biological processes. Meanwhile, the main chemical components were identified as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E by batch molecular docking strategy. Further, the in vitro experiments demonstrated that BYHWD not only regulated macrophage polarization and alleviated macrophage foam formation but also modulated mitochondrial function and the expression of TP53, p-AKT, and BCL2 proteins. Finally, multivariate statistical analysis confirmed that the ameliorative effect of BYHWD on AS was closely related to mitochondrial function and macrophage polarization regulated by TP53, AKT1 and BCL2.</p><p><strong>Conclusions: </strong>BYHWD could activate key targets, including TP53, AKT1, and BCL2, to alleviate mitochondrial dysfunction and regulate macrophage polarization, thereby improving AS. The 10 active compounds of BYHWD, including 5-hydroxy-L-tryptophan zwitterion and Isoliquiritigenin, played an important role in regulating macrophages polarization to alleviate AS.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119152"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695639","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":"Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2","authors":"Jialei Song ,&nbsp;Wuling Liu ,&nbsp;Xiao Xiao ,&nbsp;Jingrui Song ,&nbsp;Chunlin Wang ,&nbsp;Babu Gajendran ,&nbsp;Xuenai Wei ,&nbsp;Changfu Yang ,&nbsp;Yunzhi Chen ,&nbsp;Yiying Yang ,&nbsp;Lei Huang ,&nbsp;Junrong Song ,&nbsp;Yaacov Ben-David ,&nbsp;Yanmei Li","doi":"10.1016/j.jep.2024.119145","DOIUrl":"10.1016/j.jep.2024.119145","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;The theory of traditional Chinese medicine (TCM) views leukemia as an imbalance between cell growth and death mainly caused by blood stasis. Medicinal plants &lt;em&gt;Aglaia&lt;/em&gt; Lour. (family Meliaceae) are traditionally used as folk medicine in China. It possesses the effects of removing blood stasis and swelling for treatment of cancer. Rocaglamide (RocA) is the main active phytochemical component of the genus &lt;em&gt;Aglaia&lt;/em&gt; Lour. Possessing highly anti-leukemia properties. However, the molecular mechanisms by which RocA exerts its anti-growth effect on erythroleukemia cells are largely unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study aimed to explore the underlying mechanism and glucose metabolism regulation effects of RocA responsible for its anti-erythroleukemia activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Human erythroleukemic cells were tested for glucose metabolism and treated with glucose deprivation and RocA. MTT assay, cell cycle and apoptosis were used to elucidate growth inhibition. Glucose uptake, glucose consumption and lactate production were evaluated for identification of glucose metabolism. Luciferase assay and ChIP were used to examine the transcriptional activity of c-MYC on the conserved E-boxes binding of the &lt;em&gt;TXNIP&lt;/em&gt; (&lt;em&gt;thioredoxin-interacting protein&lt;/em&gt;) and &lt;em&gt;HK2&lt;/em&gt; (&lt;em&gt;hexokinase 2&lt;/em&gt;) &lt;em&gt;genes&lt;/em&gt;. siRNA, shRNA and exogenous transfection were employed to elucidate the effects of TXNIP and HK2 on glucose metabolism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We find that glucose deprivation results in growth inhibition, cell cycle arrest and extensive apoptosis in erythroleukemic cells accompanied by downregulation of c-MYC and HK2, responsible for glucose metabolism. The similar results emerged in RocA treated erythroleukemic cells in presence of glucose. RocA is shown to decrease glucose uptake, glucose consumption and lactate production. Mechanistically, RocA dramatically increases TXNIP expression through interference with c-MYC binding to the promoter of the &lt;em&gt;TXNIP&lt;/em&gt; gene. RocA also represses c-MYC transcriptional recognition of conserved E-boxes in the &lt;em&gt;HK2&lt;/em&gt; first intron, resulting in HK2 loss. These results implicate c-MYC as an important regulator of TXNIP and HK2 after RocA treatment. TXNIP overexpression or knockdown of HK2 suppresses the proliferation of erythroleukemic cells. Ectopic TXNIP expression restricts glucose uptake and HK2 suppression decreases glucose utilization. Further, our data suggests that loss of HK2 weakens the RocA-driven inhibition effects. We propose repression of c-MYC or the binding by RocA upregulates TXNIP and downregulates HK2, possibly contributes to growth inhibition in human erythroleukemic cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study uncovers molecular mechanism of RocA against leukemic cells proliferation, linking the anti-erythroleukemia properties of RocA to","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119145"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695683","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":"Exploring the structure-activity relationship of Safflower polysaccharides: From the structural characteristics to biological function and therapeutic applications","authors":"Jia-Xin Li,&nbsp;Ding-Qiao Xu,&nbsp;Dong-Xiao Cui,&nbsp;Rui-Jia Fu,&nbsp;Ze-Chen Niu,&nbsp;Wen-Juan Liu,&nbsp;Yu-Ping Tang","doi":"10.1016/j.jep.2024.119131","DOIUrl":"10.1016/j.jep.2024.119131","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Safflower, the florets of <em>Carthamus tinctorius</em> L., is a widely used traditional Chinese medicine for promoting circulation and improving dysmenorrhea. Polysaccharides is one of the principal water-soluble components in Safflower, which recently endowed with a variety of biological activities, thus making them have important research significance in the field of ethnopharmacology.</div></div><div><h3>Aim of the study</h3><div>This review summarized the latest research progress on the preparation technology, structural characteristics, and pharmacological effects of Safflower polysaccharides. Moreover, by comparing the structural characteristic of Safflower polysaccharides, the potential structure-activity relationship of Safflower polysaccharides was also discussed.</div></div><div><h3>Materials and methods</h3><div>This article used keywords including Safflower polysaccharide, <em>Carthamus tinctorius</em> L polysaccharide, Safflower polysaccharide extraction and separation, Safflower polysaccharide structure, and Safflower polysaccharide anti-tumor effects to search for all relevant literature in PubMed, Web of Science, Google Scholar, ScienceDirect, CNKI and other databases from the establishment of the database to July 2024.</div></div><div><h3>Results</h3><div>Summarizing current research findings, seventeen homogeneous Safflower polysaccharides have been obtained. Their structural characteristics, including molecular weights, monosaccharide composition, sugar residue types, glycosidic bond configuration, and the linkage sequence, were initially researched. In terms of pharmacological activity, Safflower polysaccharides exhibit a wide range of biological activities, including immune regulation, anti-tumor effects, and antioxidant properties. Furthermore, the structural characteristics of Safflower polysaccharides significantly influence its biological activities, encompassing factors such as molecular weight, monosaccharide composition, and degree of branching.</div></div><div><h3>Conclusion</h3><div>Safflower polysaccharides have seen significant advancements in recent years regarding preparation methods, structural characterization, and pharmacological studies. These achievements would provide a theoretical basis for the application of Safflower polysaccharide in the field of ethnopharmacology. While Safflower polysaccharides exhibit diverse biological activities and significant potential for development and utilization, further in-depth research is needed to enhance our understanding of their mechanisms of action and optimize their clinical applications.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119131"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693038","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":"Gualou Xiebai Banxia Decoction suppresses cardiomyocyte apoptosis in mice after myocardial infarction through activation of acetaldehyde dehydrogenase 2","authors":"Bingying Deng ,&nbsp;Guoyong Zhang ,&nbsp;Yixuan Zeng ,&nbsp;Nireng Li ,&nbsp;Changlei Hu ,&nbsp;Mingjie Pang ,&nbsp;Sifan Lu ,&nbsp;Yufeng Gu ,&nbsp;Guanghong Chen ,&nbsp;Yingchun Zhou ,&nbsp;Yi Liu ,&nbsp;Yue Hua","doi":"10.1016/j.jep.2024.119143","DOIUrl":"10.1016/j.jep.2024.119143","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Cardiac apoptosis has been reported to be involved in the development of Heart failure (HF) after Myocardial infarction (MI). As a traditional Chinese medicine with cardioprotective properties, Gualou Xiebai Banxia Decoction (GXBD) is therapeutically effective in treating MI. However, whether GXBD regulates cardiac apoptosis in HF after MI remains unknown, and the underlying mechanisms still unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.</div></div><div><h3>Materials and methods</h3><div>The MI model was constructed by ligating the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of GXBD were determined by echocardiography, masson staining, and haematoxylin and eosin (HE) staining. Bioinformatics analysis and network Pharmacology were used to explore the underlying molecular mechanisms of GXBD in MI. The effects of GXBD on cardiomyocyte apoptosis as well as the ALDH2 were examined by TUNEL staining, Immunohistochemistry (IHC), and Western blot (WB). Additionally, the effects of GXBD on oxidative stress, apoptosis and the ALDH2 in H9c2 cells were investigated using reactive oxygen species (ROS) detection, Hoechst33342/PI stainingand and WB. Moreover, the effects of suppressing and overexpressing ALDH2 in H9c2 cells were further examined.</div></div><div><h3>Results</h3><div>Target prediction analysis showed that ALDH2 was a key target of GXBD which could ameliorate myocardial infarction. GXBD dose-dependently reduced cardiomyocyte apoptosis and ventricular dysfunction. In vivo experiments, GXBD activated ALDH2 enzymatic activity and inhibited the expression levels of Bax, Bcl-2, Cleaved Caspase 3, and Caspase 9. In vitro experiments, GXBD inhibited apoptosis in H9c2 cells. The inhibitory effects of GXBD on these were at least partially attributed to ALDH2 activation while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.</div></div><div><h3>Conclusion</h3><div>GXBD exerts inhibitory effects on cardiomyocyte apoptosis in mice after MI and suppresses H9c2 cells oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119143"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693039","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":"Multiomics and experimental approaches reveal the anti-acute lung injury effects of Fallopia aubertii (L. Henry) Holub extract via IL-17/NF-κB pathway inhibition","authors":"Shuna Liu ,&nbsp;Canchao Jia ,&nbsp;Jingxin Zhao ,&nbsp;Yue Xiong ,&nbsp;Wensi Yan ,&nbsp;Wenxiu Zhang ,&nbsp;Yichu Nie ,&nbsp;Yongbo Xue ,&nbsp;Wenbin Deng","doi":"10.1016/j.jep.2024.119123","DOIUrl":"10.1016/j.jep.2024.119123","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Fallopia aubertii</em> (L. Henry) Holub (<em>F. aubertii</em>), a traditional Tibetan medicine, is used in China for treating respiratory inflammatory diseases, including acute lung injury (ALI). However, the chemical constituents of <em>F. aubertii</em> and its anti-inflammatory mechanisms in the lungs remain poorly understood.</div></div><div><h3>Aim of the study</h3><div>This study aimed to identify the chemical constituents of the <em>F. aubertii</em> extract (FAE), evaluate its effectiveness in reducing ALI in mice, and elucidate the underlying mechanisms of its action.</div></div><div><h3>Materials and methods</h3><div>The chemical composition of FAE was determined using UPLC-LTQ Velos Pro-Orbitrap Elite. Network pharmacology was employed to predict the mechanisms by which FAE might mitigate ALI. Mice were administered FAE orally for seven days, followed by intratracheal instillation of lipopolysaccharide (LPS) to induce ALI. On the final day, the mice were euthanized, and their lungs were collected for transcriptome analysis, proteomics, pharmacodynamic evaluation, and mechanistic studies. Hematoxylin and eosin (H&amp;E) staining assessed lung pathology. Transcriptome and proteomic analyses, along with real-time quantitative PCR (RT-qPCR) and western blotting, were used to investigate FAE's effects on lung inflammation and related signaling pathways. In vitro experiments further explored the anti-ALI mechanisms of FAE. Immunofluorescence assays in RAW264.7 cells examined the nuclear translocation of NF-κB.</div></div><div><h3>Results</h3><div>Fifty-one compounds were identified in FAE, predominantly flavonoid glycosides. Network pharmacology suggested that FAE may inhibit ALI by modulating the NF-κB pathway and Th17 differentiation. RNA-seq analysis indicated that FAE might suppress inflammation through the IL-17 signaling pathway, with these findings corroborated by mRNA level measurements in vivo and in vitro. FAE alleviated LPS-induced ALI by modulating the IL-17A signaling pathway, which was confirmed through proteomic analysis. Western blotting revealed that FAE reduced the expression of IL-17A, Act1, TRAF6, and p-NF-κB, while immunofluorescence assays showed FAE inhibited LPS-induced NF-κB nuclear translocation.</div></div><div><h3>Conclusion</h3><div>FAE attenuates inflammation-mediated ALI by inhibiting the IL-17A/NF-κB signaling pathway. This study highlights the anti-ALI effects of FAE and provides a theoretical foundation for its potential use in ALI treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119123"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687138","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":"Relationship between metabolomics of T2DM patients and the anti-diabetic effects of Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma herb pair in mice","authors":"Jia-Lin Yu ,&nbsp;Zhen-Yang Zhang ,&nbsp;Sheng-Ping Liu ,&nbsp;Hong-Ping Long ,&nbsp;Ting-Ting Wang ,&nbsp;Feng-Qing Huang ,&nbsp;Jia Guo ,&nbsp;Wei-Long Xu ,&nbsp;Fei Li","doi":"10.1016/j.jep.2024.119129","DOIUrl":"10.1016/j.jep.2024.119129","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Materials and methods</h3><div>In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients.</div></div><div><h3>Results</h3><div>Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1.</div></div><div><h3>Conclusion</h3><div>PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119129"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687144","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":"Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters","authors":"Islam Husain ,&nbsp;Balkisu Abdulrahman ,&nbsp;Olivia R. Dale ,&nbsp;Kumar Katragunta ,&nbsp;Mantasha Idrisi ,&nbsp;Bill J. Gurley ,&nbsp;Zulfiqar Ali ,&nbsp;Bharathi Avula ,&nbsp;Amar G. Chittiboyina ,&nbsp;Ikhlas A. Khan ,&nbsp;Frederick Oduh Ujah ,&nbsp;Shabana I. Khan","doi":"10.1016/j.jep.2024.119142","DOIUrl":"10.1016/j.jep.2024.119142","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Phyllanthus amarus</em> is ethnomedicinally used to treat gallbladder stones, kidney stones and chronic liver diseases. <em>P. amarus</em> is gaining popularity as an ingredient in many botanical dietary supplements.</div></div><div><h3>Aim of the study</h3><div>To evaluate the interaction of <em>P. amarus</em> extract and its lignans with human xenobiotic sensing receptors (PXR and AhR) and their downstream genes.</div></div><div><h3>Materials and methods</h3><div>Activation of PXR and AhR was measured by reporter gene assays. Gene expression analysis was performed in hepatic (HepG2) and intestinal (LS174T) cells by RT-PCR. CYP inhibition assays were carried out in baculosomes. The inhibitory effect on the ABC transporters (P-gp and BCRP) was investigated via rhodamine-123 and Hoechst 33342 uptake assays in Caco-2 and MDR-MDCK cells. Effect on CYP3A4 and CYP1A2 enzyme activity was measured in primary human hepatocytes.</div></div><div><h3>Results</h3><div><em>P. amarus</em> extract and its lignans activated AhR and PXR in respective reporter cells. Tested extract and lignans significantly increased CYP3A4 mRNA but inhibited CYP3A4 enzyme activity when tested in primary human hepatocytes and CYP3A4-specific baculosomes. In contrast, increased CYP1A2 mRNA was associated with increased CYP1A2 enzyme activity in hepatocytes. No inhibition of CYP1A2 activity was detected in baculosomes. A weak inhibitory effect on ABC-transporters was observed.</div></div><div><h3>Conclusions</h3><div>Results suggest that overconsumption of <em>P. amarus</em> or <em>P. amarus</em>-containing botanical supplements may change CYP homeostasis which could alter the pharmacokinetics of substrate drugs, thereby elevating the risk of herb-drug interactions (HDIs) when taken concomitantly with conventional medications. Further studies are warranted to strengthen the clinical relevance of these findings.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119142"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687059","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":"Identification of antimalarial phytoconstituents from Tinospora sinensis (Lour.) Merr. Stem by in vitro whole cell assay and multiple targets directed in silico screening against Plasmodium falciparum","authors":"Neelutpal Gogoi ,&nbsp;Bhaskarjyoti Gogoi ,&nbsp;Partha Pratim Kaishap ,&nbsp;Dipak Chetia","doi":"10.1016/j.jep.2024.119134","DOIUrl":"10.1016/j.jep.2024.119134","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tinospora sinensis</em> (Lour.) Merr., from the family Menispermaceae, is widely used in Indian folk and Ayurvedic medicine. Indigenous tribes such as the Tea-tribe and Chorei-tribe of Assam use its bark and stem as a herbal remedy to treat malaria and it is also traditionally employed for conditions such as dyspepsia, inflammation, fever, ulcers, jaundice, diabetes and various urinary, skin, and liver diseases.</div></div><div><h3>Aim of the study</h3><div>This study aims to identify and characterize antimalarial phytoconstituents from the active extract of <em>T. sinensis</em> stem by <em>in vitro</em> screening against both the Chloroquine-sensitive (<em>Pf</em>3D7) as well as Chloroquine-resistant (<em>Pf</em>RKL-9) strains of <em>Plasmodium falciparum</em>, along with exploring potential targets and mechanisms using molecular docking and dynamics simulation studies.</div></div><div><h3>Materials and methods</h3><div><em>T. sinensis</em> stems were collected from Assam, India, and authenticated by the Botanical Survey of India. The plant materials were initially extracted with non-polar to polar solvents and screened for <em>in vitro</em> antimalarial potency against <em>Pf</em>3D7 and <em>Pf</em>RKL-9. Then, the methanol extract was selected for bioassay-guided isolation of phytoconstituent(s). The isolated phytoconstituent(s) were screened for antimalarial potential and active compounds were further evaluated for cytotoxicity using the HEK-293 cell line. Structural characterization of the active compounds involved the use of UV–VIS, IR, NMR and HRMS analyses. Molecular docking and dynamics simulation studies were performed on selected targets from <em>P. falciparum</em> to predict binding affinities and mechanisms of action.</div></div><div><h3>Results</h3><div>From the methanol extract of <em>T. sinensis</em> stem, five phytoconstituents were isolated, including isoquinoline alkaloids Berberine (NG1) and Palmatine (NG2) showed the best antimalarial activity (IC₅₀ &lt; 1 μg/ml) against both <em>Pf</em>3D7 and <em>Pf</em>RKL-9. Cytotoxicity assays confirmed their safety and selectivity. Molecular docking and dynamic simulation studies revealed that Berberine and Palmatine formed stable complexes with <em>P. falciparum</em> lysyl-tRNA synthetase and <em>P. falciparum</em> aminopeptidase N, respectively, indicating their potential as antimalarial leads.</div></div><div><h3>Conclusion</h3><div>This study identifies two potent antimalarial phytoconstituents in the stem of <em>T. sinensis</em>, validating its traditional use and demonstrating its safety and efficacy for potential global application in malaria treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119134"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681755","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":"Protective effect of Curcuma longa L. leaves and pseudostems extract against 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis in BALB/c mice","authors":"Arachchige Maheshika Kumari Jayasinghe ,&nbsp;Kirinde Gedara Isuru Sandanuwan Kirindage ,&nbsp;Sun-Hyung Kim ,&nbsp;Seok Lee ,&nbsp;Kyungsook Jung ,&nbsp;Sun-Yup Shim ,&nbsp;Ginnae Ahn","doi":"10.1016/j.jep.2024.119138","DOIUrl":"10.1016/j.jep.2024.119138","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;The perennial herbaceous plant, &lt;em&gt;Curcuma longa&lt;/em&gt; L. (turmeric) is primarily grown and harvested for pharmacological purposes in China, Korea, and various tropical regions in South Asia. Turmeric has been used for centuries as an indigenous medicine. In particular, Ayurveda has been extensively used to treat, prevent, and manage multiple illnesses, including inflammation, allergies, arthritis, cancer, diabetes, diarrhea, psoriasis, and digestive issues. Importantly, various studies have confirmed the presence of numerous active compounds with health-enhancing biological properties in turmeric leaves and pseudostems.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;Atopic dermatitis (AD) is a long-lasting inflammatory disorder that is associated with abnormalities in the immune system, such as T-helper (Th) cell dysregulation, elevated immunoglobulin (Ig) levels, inflammatory cell infiltration, and skin barrier damage. This study aimed to explore the therapeutic effects of turmeric leaves and pseudostems (CLHW) extract against AD in a BALB/c mouse disease model established using 1-chloro-2,4-dinitrobenzene (DNCB).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;AD-like symptoms were induced by topically applying DNCB to the dorsal skin of the mice, which were monitored over five weeks. Fourteen days after induction, the mice were randomly divided into different groups, and the treatment groups received daily oral gavage of CLHW for three weeks. Throughout the monitoring period, we assessed AD-like symptoms, including skin severity score, transepidermal water loss (TEWL), and scratching behavior of the mice. After measuring the body weight and ear thickness, the mice were euthanized. Furthermore, serum Ig and cytokine production levels were measured. Finally, the degrees of spleen and lymph node enlargement were evaluated, and the tissues were used for histopathological and molecular analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;CLHW improved AD-like symptoms, including skin severity score, TEWL, scratching frequency, and ear thickness in DNCB-induced AD mice. Additionally, serum levels of IgE, IgG&lt;sub&gt;1&lt;/sub&gt;, and IgG&lt;sub&gt;2a&lt;/sub&gt;, along with various inflammatory cytokines (interleukin [IL]-4, IL-5, and IL-13) and chemokines (Eotaxin and RANTES), were significantly reduced in CLHW-treated mice. CLHW decreased inflammatory cell infiltration and mast cell degranulation while downregulating mRNA expression levels of AD-related innate cytokines (thymic stromal lymphopoietin [TSLP], IL-25, IL-33), inflammatory cytokines (IL-4, IL-10, IL-13), and chemokines (thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC]) in the dorsal skin. Furthermore, CLHW reduced spleen and lymph node enlargement and downregulated mRNA expression levels of inflammatory cytokines in these tissues in a dose-dependent manner.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The results demonstrated that","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119138"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681778","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}