Pub Date : 2024-11-20DOI: 10.1016/j.jep.2024.119123
Shuna Liu , Canchao Jia , Jingxin Zhao , Yue Xiong , Wensi Yan , Wenxiu Zhang , Yichu Nie , Yongbo Xue , Wenbin Deng
Ethnopharmacological relevance
Fallopia aubertii (L. Henry) Holub (F. aubertii), a traditional Tibetan medicine, is used in China for treating respiratory inflammatory diseases, including acute lung injury (ALI). However, the chemical constituents of F. aubertii and its anti-inflammatory mechanisms in the lungs remain poorly understood.
Aim of the study
This study aimed to identify the chemical constituents of the F. aubertii extract (FAE), evaluate its effectiveness in reducing ALI in mice, and elucidate the underlying mechanisms of its action.
Materials and methods
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&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.
Results
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.
Conclusion
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.
民族药理学意义：Fallopia aubertii (L. Henry) Holub（F. aubertii）是一种传统藏药，在中国被用于治疗呼吸道炎症性疾病，包括急性肺损伤（ALI）。然而，人们对 F. aubertii 的化学成分及其在肺部的抗炎机制仍知之甚少：研究目的：本研究旨在确定欧鼠尾草提取物（FAE）的化学成分，评估其降低小鼠 ALI 的效果，并阐明其作用的基本机制：材料和方法：采用 UPLC-LTQ Velos Pro-Orbitrap Elite 高效液相色谱法测定白花前胡提取物的化学成分。采用网络药理学预测 FAE 缓解 ALI 的机制。给小鼠口服FAE七天，然后气管内灌注脂多糖（LPS）诱发ALI。最后一天，小鼠安乐死，收集其肺部进行转录组分析、蛋白质组学研究、药效学评估和机理研究。血红素和伊红（H&E）染色评估肺部病理学。转录组和蛋白质组分析以及实时定量 PCR（RT-qPCR）和 Western 印迹技术用于研究 FAE 对肺部炎症和相关信号通路的影响。体外实验进一步探索了 FAE 的抗 ALI 机制。在 RAW264.7 细胞中进行的免疫荧光实验检测了 NF-κB 的核转位：结果：在 FAE 中发现了 51 种化合物，主要是黄酮苷。网络药理学表明，FAE 可通过调节 NF-κB 通路和 Th17 分化来抑制 ALI。RNA-seq分析表明，FAE可能通过IL-17信号通路抑制炎症，体内和体外的mRNA水平测量也证实了这些发现。FAE通过调节IL-17A信号通路缓解了LPS诱导的ALI，蛋白质组分析证实了这一点。Western印迹分析表明，FAE降低了IL-17A、Act1、TRAF6和p-NF-κB的表达，而免疫荧光分析表明，FAE抑制了LPS诱导的NF-κB核转位：结论：FAE通过抑制IL-17A/NF-κB信号通路来减轻炎症介导的ALI。本研究强调了 FAE 的抗 ALI 作用，并为其在 ALI 治疗中的潜在应用提供了理论基础。
{"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 , Canchao Jia , Jingxin Zhao , Yue Xiong , Wensi Yan , Wenxiu Zhang , Yichu Nie , Yongbo Xue , 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&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}
Ethnopharmacological relevance: 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.
Aim of the study: This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.
Materials and methods: 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 hematoxylin 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 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 cardiomyocytes (H9c2) 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.
Results: 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. ALDH2 activation enhanced these inhibitory effects of GXBD while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.
Conclusion: GXBD exerts inhibitory effects on oxidative stress and cardiomyocyte apoptosis in mice after MI, suppresses H9c2 oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.
{"title":"Gualou Xiebai Banxia Decoction Suppresses Cardiac Apoptosis in Mice after Myocardial Infarction through Activation of Acetaldehyde Dehydrogenase 2.","authors":"Bingying Deng, Guoyong Zhang, Yixuan Zeng, Nireng Li, Changlei Hu, Mingjie Pang, Sifan Lu, Yufeng Gu, Guanghong Chen, Yingchun Zhou, Yi Liu, Yue Hua","doi":"10.1016/j.jep.2024.119143","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119143","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.</p><p><strong>Materials and methods: </strong>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 hematoxylin 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 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 cardiomyocytes (H9c2) 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.</p><p><strong>Results: </strong>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. ALDH2 activation enhanced these inhibitory effects of GXBD while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.</p><p><strong>Conclusion: </strong>GXBD exerts inhibitory effects on oxidative stress and cardiomyocyte apoptosis in mice after MI, suppresses H9c2 oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119143"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","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}
Ethnopharmacological relevance: Safflower, the florets of Carthamus tinctorius 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.
Aim of the study: 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.
Materials and methods: This article used keywords including Safflower polysaccharide, Carthamus tinctorius 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.
Results: 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.
Conclusion: 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.
民族药理学意义：红花（Carthamus tinctorius L.的小花）是一种广泛使用的传统中药，具有促进血液循环和改善痛经的作用。多糖是红花中的主要水溶性成分之一，具有多种生物活性，因此在民族药理学领域具有重要的研究意义：本综述总结了红花多糖的制备技术、结构特征和药理作用等方面的最新研究进展。研究目的：综述了红花多糖制备技术、结构特征、药理作用等方面的最新研究进展，并通过比较红花多糖的结构特征，探讨了红花多糖潜在的结构-活性关系：本文以红花多糖、荠菜多糖、红花多糖提取分离、红花多糖结构、红花多糖抗肿瘤作用等为关键词，在PubMed、Web of Science、Google Scholar、ScienceDirect、CNKI等数据库中检索了自数据库建立至2024年7月的所有相关文献：结果：综合目前的研究成果，共获得 17 种均相红花多糖。初步研究了它们的结构特征，包括分子量、单糖组成、糖残基类型、糖苷键构型和连接序列。在药理活性方面，红花多糖具有广泛的生物活性，包括免疫调节、抗肿瘤作用和抗氧化性。此外，红花多糖的结构特征对其生物活性有显著影响，包括分子量、单糖组成和分支程度等因素：近年来，红花多糖在制备方法、结构表征和药理研究方面取得了重大进展。这些成果为红花多糖在民族药理学领域的应用提供了理论依据。红花多糖具有多种生物活性，具有巨大的开发和利用潜力，但还需要进一步深入研究，以加深对其作用机制的了解，优化其临床应用。
{"title":"Exploring the Structure-Activity Relationship of Safflower Polysaccharides: From the Structural Characteristics to Biological Function and Therapeutic Applications.","authors":"Jia-Xin Li, Ding-Qiao Xu, Dong-Xiao Cui, Rui-Jia Fu, Ze-Chen Niu, Wen-Juan Liu, Yu-Ping Tang","doi":"10.1016/j.jep.2024.119131","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119131","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Safflower, the florets of Carthamus tinctorius 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.</p><p><strong>Aim of the study: </strong>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.</p><p><strong>Materials and methods: </strong>This article used keywords including Safflower polysaccharide, Carthamus tinctorius 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119131"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","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}
Pub Date : 2024-11-20DOI: 10.1016/j.jep.2024.119141
Jiwon Park, Ji-Woon Jeong, Ji-Ae Roh, Beom-Joon Lee, Kwan-Il Kim, Hee-Jae Jung
{"title":"Corrigendum to \"Efficacy and safety of Sipjeondaebo-tang for cancer-related fatigue: A systematic review and meta-analysis\" [J. Ethnopharmacol. 337 (2025) 118900].","authors":"Jiwon Park, Ji-Woon Jeong, Ji-Ae Roh, Beom-Joon Lee, Kwan-Il Kim, Hee-Jae Jung","doi":"10.1016/j.jep.2024.119141","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119141","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119141"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686999","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}
Pub Date : 2024-11-19DOI: 10.1016/j.jep.2024.119142
Islam Husain , Balkisu Abdulrahman , Olivia R. Dale , Kumar Katragunta , Mantasha Idrisi , Bill J. Gurley , Zulfiqar Ali , Bharathi Avula , Amar G. Chittiboyina , Ikhlas A. Khan , Frederick Oduh Ujah , Shabana I. Khan
Ethnopharmacological relevance
Phyllanthus amarus is ethnomedicinally used to treat gallbladder stones, kidney stones and chronic liver diseases. P. amarus is gaining popularity as an ingredient in many botanical dietary supplements.
Aim of the study
To evaluate the interaction of P. amarus extract and its lignans with human xenobiotic sensing receptors (PXR and AhR) and their downstream genes.
Materials and methods
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.
Results
P. amarus 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.
Conclusions
Results suggest that overconsumption of P. amarus or P. amarus-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.
{"title":"Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters","authors":"Islam Husain , Balkisu Abdulrahman , Olivia R. Dale , Kumar Katragunta , Mantasha Idrisi , Bill J. Gurley , Zulfiqar Ali , Bharathi Avula , Amar G. Chittiboyina , Ikhlas A. Khan , Frederick Oduh Ujah , 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}
Tinospora sinensis (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.
Aim of the study
This study aims to identify and characterize antimalarial phytoconstituents from the active extract of T. sinensis stem by in vitro screening against both the Chloroquine-sensitive (Pf3D7) as well as Chloroquine-resistant (PfRKL-9) strains of Plasmodium falciparum, along with exploring potential targets and mechanisms using molecular docking and dynamics simulation studies.
Materials and methods
T. sinensis 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 in vitro antimalarial potency against Pf3D7 and PfRKL-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 P. falciparum to predict binding affinities and mechanisms of action.
Results
From the methanol extract of T. sinensis stem, five phytoconstituents were isolated, including isoquinoline alkaloids Berberine (NG1) and Palmatine (NG2) showed the best antimalarial activity (IC50 < 1 μg/ml) against both Pf3D7 and PfRKL-9. Cytotoxicity assays confirmed their safety and selectivity. Molecular docking and dynamic simulation studies revealed that Berberine and Palmatine formed stable complexes with P. falciparum lysyl-tRNA synthetase and P. falciparum aminopeptidase N, respectively, indicating their potential as antimalarial leads.
Conclusion
This study identifies two potent antimalarial phytoconstituents in the stem of T. sinensis, validating its traditional use and demonstrating its safety and efficacy for potential global application in malaria treatment.
{"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 , Bhaskarjyoti Gogoi , Partha Pratim Kaishap , 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 (IC<sub>50</sub> < 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}
<div><h3>Ethnopharmacological relevance</h3><div>The perennial herbaceous plant, <em>Curcuma longa</em> 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.</div></div><div><h3>Aim of the study</h3><div>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).</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sub>1</sub>, and IgG<sub>2a</sub>, 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.</div></div><div><h3>Conclusion</h3><div>The results demonstrated that
民族药理学意义：姜黄（Curcuma longa L.）是一种多年生草本植物，主要在中国、韩国和南亚多个热带地区种植和收获，用于药用目的。几个世纪以来，姜黄一直被用作本土药物。阿育吠陀尤其广泛用于治疗、预防和控制多种疾病，包括炎症、过敏、关节炎、癌症、糖尿病、腹泻、牛皮癣和消化问题。重要的是，多项研究证实，姜黄叶和假茎中含有大量具有增强健康生物特性的活性化合物：特应性皮炎（AD）是一种持续时间较长的炎症性疾病，与免疫系统异常有关，如 T 辅助细胞（Th）失调、免疫球蛋白（Ig）水平升高、炎症细胞浸润和皮肤屏障受损。本研究旨在探讨姜黄叶和假茎（CLHW）提取物在使用 1-氯-2,4-二硝基苯（DNCB）建立的 BALB/c 小鼠疾病模型中对 AD 的治疗效果：在小鼠背侧皮肤局部涂抹DNCB，诱导小鼠出现类似AD的症状，并对其进行为期五周的监测。诱导14天后，将小鼠随机分为不同组，治疗组每天口服CLHW，连续三周。在整个监测期间，我们评估了类似 AD 的症状，包括皮肤严重程度评分、经表皮失水（TEWL）和小鼠的抓挠行为。在测量体重和耳厚后，小鼠被安乐死。此外，还测量了血清 Ig 和细胞因子的分泌水平。最后，对脾脏和淋巴结肿大程度进行评估，并对组织进行组织病理学和分子分析：结果：CLHW改善了DNCB诱导的AD小鼠的AD样症状，包括皮肤严重程度评分、TEWL、搔抓频率和耳厚。此外，CLHW 治疗小鼠血清中的 IgE、IgG1 和 IgG2a 水平以及各种炎症细胞因子（白细胞介素 [IL]-4、IL-5 和 IL-13）和趋化因子（Eotaxin 和 RANTES）均显著降低。CLHW 可减少炎症细胞浸润和肥大细胞脱颗粒，同时下调 AD 相关先天性细胞因子（胸腺基质淋巴细胞生成素 [TSLP]、IL-25、IL-33）、炎症细胞因子（IL-4、IL-10、IL-13）和趋化因子（胸腺和活化调节趋化因子 [TARC]、巨噬细胞衍生趋化因子 [MDC]）在背侧皮肤中的 mRNA 表达水平。此外，CLHW 还能减少脾脏和淋巴结肿大，并以剂量依赖的方式下调这些组织中炎症细胞因子的 mRNA 表达水平：结果表明，CLHW 能通过降低皮肤严重程度评分、TEWL、搔抓、耳厚度、血清 Ig 水平、炎症细胞浸润、肥大细胞脱颗粒以及脾脏和淋巴结肿大，有效抑制 DNCB 诱导的 AD 类症状。我们的研究结果凸显了白花蛇舌草在治疗与 AD 相关的异常免疫反应方面的民族药理学潜力。
{"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 , Kirinde Gedara Isuru Sandanuwan Kirindage , Sun-Hyung Kim , Seok Lee , Kyungsook Jung , Sun-Yup Shim , Ginnae Ahn","doi":"10.1016/j.jep.2024.119138","DOIUrl":"10.1016/j.jep.2024.119138","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The perennial herbaceous plant, <em>Curcuma longa</em> 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.</div></div><div><h3>Aim of the study</h3><div>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).</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sub>1</sub>, and IgG<sub>2a</sub>, 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.</div></div><div><h3>Conclusion</h3><div>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}
Pub Date : 2024-11-19DOI: 10.1016/j.jep.2024.119133
Abdullah Haikal , Mona El-Neketi , Manar G. Helal , Laila A. Abou-zeid , Madiha A. Hassan , Ahmed A. Gohar
Ethnopharmacological relevance
Mentha longifolia L. has been employed to treat cough, lung inflammation, and bronchial asthma disorders.
Aim of the study
Our study was carried out to investigate the medicinal effect of the flavonoids derived from M. longifolia, specifically didymin, linarin, rutin, and TMF, as well as the whole extracts of M. longifolia subsp. typhoides and M. longifolia subsp. schimperi, in comparison to dexa, in a mice model of ovalbumin-allergic asthma (OVA).
Methods
After inhaling OVA, the mice developed acute asthma symptoms. Mice were subjected orally to Dexa and/or isolated flavonoids. The study assessed total and differential leukocyte counts, LDH concentration, and total protein concentration in BALF, reduced levels of GSH and total NOx products in lung tissues and analyzed the lung specimens by staining them with hematoxylin and eosin (H & E).
Results
Histopathological analysis of the right lung lobes demonstrated that the isolated flavonoids exhibited a significant anti-inflammatory effect higher than Dexa as shown by decreasing the overall and distinct leukocyte counts, LDH levels, and total protein levels in BALF, as compared to the OVA group (p < 0.05). TMF was the most effective and the other tested flavonoids are more effective than Dexa but less than TMF. In addition, all tested flavonoids and Dexa significantly (p < 0.05) mitigated OVA-induced oxidative stress as evidenced by diminished lung NOx level and elevated GSH level. Computational docking studies proved recognition of didymin, linarin, rutin, and TMF to the human leukocyte elastase binding sites.
Conclusion
The tested flavonoids; didymin, linarin, rutin, and TMF successfully inhibit Ova-induced allergic asthma in mice through their anti-inflammatory and antioxidant activities and may represent promising candidate as a remedy for allergic asthma.
民族药理学意义：Mentha longifolia L.被用于治疗咳嗽、肺部炎症和支气管哮喘疾病：我们的研究旨在探讨从龙胆草中提取的黄酮类化合物（特别是地丁、亚麻仁、芦丁和 TMF）以及龙胆草亚种和龙胆草亚种的全提取物与地塞米松相比，在卵清蛋白过敏性哮喘（OVA）小鼠模型中的药用效果：方法：小鼠吸入 OVA 后出现急性哮喘症状。小鼠口服地塞米松和/或分离的黄酮类化合物。研究评估了白细胞总数和差值、LDH 浓度、BALF 中的总蛋白浓度、肺组织中 GSH 和总氮氧化物产物的降低水平，并用血色素和伊红（H & E）染色分析了肺部标本：右肺叶的组织病理学分析表明，与 OVA 组相比，分离出的黄酮类化合物降低了 BALF 中的白细胞总数和不同白细胞计数、LDH 水平和总蛋白水平（p< 0.05），显示其显著的抗炎效果高于地塞米松（Dexa）。TMF的效果最好，其他测试的黄酮类化合物的效果高于Dexa，但低于TMF。此外，所有测试的黄酮类化合物和 Dexa 都能显著（p< 0.05）减轻 OVA 诱导的氧化应激，肺 NOx 水平降低和 GSH 水平升高就是证明。计算对接研究证明，地黄素、亚麻仁素、芦丁和TMF与白三烯酯酶结合位点相识别：结论：所测试的黄酮类化合物（地黄素、亚麻仁素、芦丁和 TMF）通过其抗炎和抗氧化活性成功地抑制了卵巢诱导的小鼠过敏性哮喘，可作为治疗过敏性哮喘的药物。
{"title":"Anti-asthmatic and antioxidant activity of flavonoids isolated from Mentha longifolia subspecies typhoides (Briq.) Harley. and Mentha longifolia subspecies schimperi (Briq.) Briq. on ovalbumin-induced allergic asthma in mice: In-vivo and in-silico study","authors":"Abdullah Haikal , Mona El-Neketi , Manar G. Helal , Laila A. Abou-zeid , Madiha A. Hassan , Ahmed A. Gohar","doi":"10.1016/j.jep.2024.119133","DOIUrl":"10.1016/j.jep.2024.119133","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Mentha longifolia</em> L. has been employed to treat cough, lung inflammation, and bronchial asthma disorders.</div></div><div><h3>Aim of the study</h3><div>Our study was carried out to investigate the medicinal effect of the flavonoids derived from <em>M. longifolia</em>, specifically didymin, linarin, rutin, and TMF, as well as the whole extracts of <em>M. longifolia</em> subsp. <em>typhoides</em> and <em>M. longifolia</em> subsp. <em>schimperi,</em> in comparison to dexa, in a mice model of ovalbumin-allergic asthma (OVA).</div></div><div><h3>Methods</h3><div>After inhaling OVA, the mice developed acute asthma symptoms. Mice were subjected orally to Dexa and/or isolated flavonoids. The study assessed total and differential leukocyte counts, LDH concentration, and total protein concentration in BALF, reduced levels of GSH and total NOx products in lung tissues and analyzed the lung specimens by staining them with hematoxylin and eosin (H & E).</div></div><div><h3>Results</h3><div>Histopathological analysis of the right lung lobes demonstrated that the isolated flavonoids exhibited a significant anti-inflammatory effect higher than Dexa as shown by decreasing the overall and distinct leukocyte counts, LDH levels, and total protein levels in BALF, as compared to the OVA group (p < 0.05). TMF was the most effective and the other tested flavonoids are more effective than Dexa but less than TMF. In addition, all tested flavonoids and Dexa significantly (p < 0.05) mitigated OVA-induced oxidative stress as evidenced by diminished lung NOx level and elevated GSH level. Computational docking studies proved recognition of didymin, linarin, rutin, and TMF to the human leukocyte elastase binding sites.</div></div><div><h3>Conclusion</h3><div>The tested flavonoids; didymin, linarin, rutin, and TMF successfully inhibit Ova-induced allergic asthma in mice through their anti-inflammatory and antioxidant activities and may represent promising candidate as a remedy for allergic asthma.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119133"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686995","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}
Pub Date : 2024-11-19DOI: 10.1016/j.jep.2024.119110
Ruochong Wang , Yan Liu , Yang Jiang , Yawen Zhang , Yifei Zhang , Binshi Wang , Haixin Lu , Hui Su , Wenyong Liao , Leilei Liu , Feng Li , Weiyue Zhang , Shuran Ma
Ethnopharmacological relevance
Shenling Baizhu San (SLBZS) is a Traditional Chinese Medicine (TCM) formula composed of 10 medicinal herbs, historically used to strengthen the spleen, replenish qi, and alleviate fatigue-related symptoms. SLBZS originates from the 'Taiping Huimin Heji Ju Fang' of the Song Dynasty. Central fatigue (CF), a subtype of fatigue, is considered in TCM to be closely associated with spleen deficiency. However, there is currently a lack of research on SLBZS's therapeutic effects on CF and the pharmacological mechanisms underlying its potential benefits.
Aim of the study
This study aims to assess the effects of SLBZS on CF in rats induced by the Modified Multiple Platform Method (MMPM) and to elucidate the underlying mechanisms, focusing on mitochondrial biogenesis and SIRT1/PGC-1α pathway regulation.
Materials and methods
CF was induced in male Wistar rats using MMPM, involving intermittent sleep deprivation over 21 days. SLBZS was administered at low(LSLBZS), medium(MSLBZS), and high doses(HSLBZS). Chemical components of SLBZS were identified and quantified using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS). Behavioral tests evaluated physical performance, emotional state, and cognitive function, while serum biochemical markers, mitochondrial morphology, and the protein and gene expression levels of the SIRT1/PGC-1α pathway were analyzed to explore underlying mechanisms.
Results
A total of 141 main compounds in SLBZS were identified, comprising various components such as flavonoids, phenylpropanoids, terpenoids, among others. SLBZS significantly improved physical performance, alleviated negative emotions, and enhanced cognitive function in CF rats. Biochemically, SLBZS increased serum ATP levels and reduced fatigue-related markers. Mitochondrial analysis demonstrated that SLBZS reversed mitochondrial degeneration, increased mitochondrial number, and increased mtDNA copy number in the hippocampus. Furthermore, SLBZS upregulated SIRT1/PGC-1α pathway expression at both the protein and gene levels in the hippocampus. Notably, the HSLBZS group demonstrated particularly pronounced effects.
Conclusion
SLBZS significantly alleviates CF symptoms enhances mitochondrial function via upregulating the SIRT1/PGC-1α pathway, positioning it as a promising alternative for CF management by addressing both its physiological and symptomatic aspects.
{"title":"Shenling Baizhu San alleviates central fatigue through SIRT1-PGC-1α-Mediated mitochondrial biogenesis","authors":"Ruochong Wang , Yan Liu , Yang Jiang , Yawen Zhang , Yifei Zhang , Binshi Wang , Haixin Lu , Hui Su , Wenyong Liao , Leilei Liu , Feng Li , Weiyue Zhang , Shuran Ma","doi":"10.1016/j.jep.2024.119110","DOIUrl":"10.1016/j.jep.2024.119110","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shenling Baizhu San (SLBZS) is a Traditional Chinese Medicine (TCM) formula composed of 10 medicinal herbs, historically used to strengthen the spleen, replenish qi, and alleviate fatigue-related symptoms. SLBZS originates from the 'Taiping Huimin Heji Ju Fang' of the Song Dynasty. Central fatigue (CF), a subtype of fatigue, is considered in TCM to be closely associated with spleen deficiency. However, there is currently a lack of research on SLBZS's therapeutic effects on CF and the pharmacological mechanisms underlying its potential benefits.</div></div><div><h3>Aim of the study</h3><div>This study aims to assess the effects of SLBZS on CF in rats induced by the Modified Multiple Platform Method (MMPM) and to elucidate the underlying mechanisms, focusing on mitochondrial biogenesis and SIRT1/PGC-1α pathway regulation.</div></div><div><h3>Materials and methods</h3><div>CF was induced in male Wistar rats using MMPM, involving intermittent sleep deprivation over 21 days. SLBZS was administered at low(LSLBZS), medium(MSLBZS), and high doses(HSLBZS). Chemical components of SLBZS were identified and quantified using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS). Behavioral tests evaluated physical performance, emotional state, and cognitive function, while serum biochemical markers, mitochondrial morphology, and the protein and gene expression levels of the SIRT1/PGC-1α pathway were analyzed to explore underlying mechanisms.</div></div><div><h3>Results</h3><div>A total of 141 main compounds in SLBZS were identified, comprising various components such as flavonoids, phenylpropanoids, terpenoids, among others. SLBZS significantly improved physical performance, alleviated negative emotions, and enhanced cognitive function in CF rats. Biochemically, SLBZS increased serum ATP levels and reduced fatigue-related markers. Mitochondrial analysis demonstrated that SLBZS reversed mitochondrial degeneration, increased mitochondrial number, and increased mtDNA copy number in the hippocampus. Furthermore, SLBZS upregulated SIRT1/PGC-1α pathway expression at both the protein and gene levels in the hippocampus. Notably, the HSLBZS group demonstrated particularly pronounced effects.</div></div><div><h3>Conclusion</h3><div>SLBZS significantly alleviates CF symptoms enhances mitochondrial function via upregulating the SIRT1/PGC-1α pathway, positioning it as a promising alternative for CF management by addressing both its physiological and symptomatic aspects.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119110"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687148","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}
Pub Date : 2024-11-19DOI: 10.1016/j.jep.2024.119139
Jiali Liu, Li Ji, Yue Wang, Xingrui Chen, Yemin Wan, Haihua Qian, Dan Zhang
Ethnopharmacological relevance: Tongbian Decoction (TBD) is a traditional Chinese botanical drug preparation which has been reported to improve constipation in patients. Due to the lack of a well-understood action mechanism of TBD, we examined the effects of TBD in cell autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian aimed of rapamycin (PI3K/Akt/mTOR) signaling pathway associated with constipation.
Aim of this study: To determine the mechanism which underlined the effects of TBD for activating PI3K/AKT/mTOR signaling pathway to inhibit the autophagy in rat.
Methods: In this study, we fed the rat with forage containing compound diphenoxylate 8mg/kg/day for 120 days, to finish the establishment of a constipation rat model. Subsequently, The constipation rats from all TBD group (TBD-Low group, TBD-Medium group, TBD-High group) were intragastrically administered with different dose (TBD-L, 1.3g/mL; TBD-M, 2.7g/mL; TBD-H, 5.3g/mL) for 28 days, and their general condition, fecal moisture percentage, intestinal propulsion and pathological morphology were observed. In addition, Neuropeptid and Gastrointestinal hormones were detected by ELISA, and the inspection of protein 1A/1B-light chain 3 (LC3) -II/I, Beclin1, p62, and PI3K/AKT/mTOR was done with the utility of western blotting and qPCR.
Results: In this study, TBD was shown to be able to improve general condition, intestinal function, and reduce inflammatory cell infiltration, whereas ELISA indicated that TBD can regulate the levels of gastrointestinal hormones, increase5-hydroxytryptamine (5-HT), substance P (SP) and decrease neuropeptide Y(NPY), calcitonin gene related peptide(CGRP) morphology. Meanwhile, TBD can also decrease Beclin 1 level and LC3Ⅱ/I ratio, and increase p62 level, which inhibit the cell autophagy, and increase the phosphorylation level of p-PI3/PI3K, p-AKT/AKT and p-mTOR/mTOR in colon tissue.
Conclusion: These results found that TBD can regulate the expression of Neuropeptid and Gastrointestinal hormones to activate PI3K/AKT/mTOR signaling pathway, and inhibit the cell autophagy to enhance the function of intestinal transmission.
{"title":"Tongbian Decoction Inhibits Cell Autophagy via PI3K/Akt/mTOR Signaling Pathway to Treat Constipation Rats.","authors":"Jiali Liu, Li Ji, Yue Wang, Xingrui Chen, Yemin Wan, Haihua Qian, Dan Zhang","doi":"10.1016/j.jep.2024.119139","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119139","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Tongbian Decoction (TBD) is a traditional Chinese botanical drug preparation which has been reported to improve constipation in patients. Due to the lack of a well-understood action mechanism of TBD, we examined the effects of TBD in cell autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian aimed of rapamycin (PI3K/Akt/mTOR) signaling pathway associated with constipation.</p><p><strong>Aim of this study: </strong>To determine the mechanism which underlined the effects of TBD for activating PI3K/AKT/mTOR signaling pathway to inhibit the autophagy in rat.</p><p><strong>Methods: </strong>In this study, we fed the rat with forage containing compound diphenoxylate 8mg/kg/day for 120 days, to finish the establishment of a constipation rat model. Subsequently, The constipation rats from all TBD group (TBD-Low group, TBD-Medium group, TBD-High group) were intragastrically administered with different dose (TBD-L, 1.3g/mL; TBD-M, 2.7g/mL; TBD-H, 5.3g/mL) for 28 days, and their general condition, fecal moisture percentage, intestinal propulsion and pathological morphology were observed. In addition, Neuropeptid and Gastrointestinal hormones were detected by ELISA, and the inspection of protein 1A/1B-light chain 3 (LC3) -II/I, Beclin1, p62, and PI3K/AKT/mTOR was done with the utility of western blotting and qPCR.</p><p><strong>Results: </strong>In this study, TBD was shown to be able to improve general condition, intestinal function, and reduce inflammatory cell infiltration, whereas ELISA indicated that TBD can regulate the levels of gastrointestinal hormones, increase5-hydroxytryptamine (5-HT), substance P (SP) and decrease neuropeptide Y(NPY), calcitonin gene related peptide(CGRP) morphology. Meanwhile, TBD can also decrease Beclin 1 level and LC3Ⅱ/I ratio, and increase p62 level, which inhibit the cell autophagy, and increase the phosphorylation level of p-PI3/PI3K, p-AKT/AKT and p-mTOR/mTOR in colon tissue.</p><p><strong>Conclusion: </strong>These results found that TBD can regulate the expression of Neuropeptid and Gastrointestinal hormones to activate PI3K/AKT/mTOR signaling pathway, and inhibit the cell autophagy to enhance the function of intestinal transmission.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119139"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687151","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}
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