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Network Pharmacology-based Analysis to Investigate Bioactive from the Root of Astragalus membranaceus against Immunomodulatory Protein and their Role in Autoimmune Thyroiditis (AIT) 基于网络药理学的黄芪根抗免疫调节蛋白活性及其在自身免疫性甲状腺炎中的作用研究
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-26 DOI: 10.1177/09731296231189561
Yi Wen, Changda Li, Yifan Zeng, Chanyuan Zhou, Qiang Zhang, Tianshu Gao
Background The thyroid is the prime organ of infection during the onset of autoimmune disease. The disease is known as Autoimmune thyroiditis (AIT). In recent times, AIT has been alarming worldwide, with growing attention towards pharmaceutical companies for finding new drugs for therapy. The present investigation aims to use a multi-targeting approach to identify the best compound from the root of Astragalus membranaceus for synergistic therapy of AIT. Materials and Methods To explore the mechanism of action of the compounds, the present study uses network pharmacology-based methods. Totally, 48 genes involved in AIT were collected from the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Gene ontology (GO) annotation, disease ontology, and pathway enrichment analysis were conducted. The chemical structure of the compounds from A. membranaceus was retrieved from the PubChem database. To study the toxic and pharmacological efficiency of the chemical structure, absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening was performed. Results The ononin and astroside were identified as suitable with all the pharmacokinetic properties can be employed to identify the disease targets. The intersection between the compound target (C-T-N) and the AIT-related genes was identified. Totally 16 genes among the C-T networks of ononin and astroside have shown interaction with thyroid disease-related pathways and signaling pathways. Consequently, the overlapping genes between the C-T network and AIT-related genes were determined as IL2. However, from the pathway enrichment, AIT-related genes have been involved in several viral infection pathways. The genes involved in infection pathways are also targeted by ononin and astroside. Conclusion The underlying mechanism of action of the compounds on AIT-related pathways was also determined. Therefore, a network pharmacology-based strategy will provide new insight into AIT therapy. However, further studies are required to validate the investigation that can prove bioactive as a promising candidate for the treatment of AIT.
背景:甲状腺是自身免疫性疾病发病时的主要感染器官。这种疾病被称为自身免疫性甲状腺炎(AIT)。近年来,随着越来越多的人关注制药公司寻找新的治疗药物,美国在台协会在全球范围内引起了警惕。本研究旨在采用多靶点方法,从黄芪根中寻找增效治疗AIT的最佳化合物。材料与方法为探索化合物的作用机制,本研究采用基于网络药理学的方法。从京都基因与基因组百科全书通路(KEGG)中共收集到48个参与AIT的基因。进行了基因本体(GO)注释、疾病本体和途径富集分析。从PubChem数据库中检索到A. membrane aceus化合物的化学结构。为了研究其化学结构、吸收、分布、代谢、排泄和毒性(ADMET)的毒性和药理作用。结果经鉴定,草柄草苷和星形草苷具有良好的药动学性质,可用于鉴定疾病靶点。发现了复合靶点(C-T-N)与ait相关基因的交集。在草皂苷和星皂苷的C-T网络中,共有16个基因与甲状腺疾病相关通路和信号通路相互作用。因此,C-T网络与ait相关基因之间的重叠基因被确定为IL2。然而,从途径富集来看,ait相关基因参与了多种病毒感染途径。与感染途径相关的基因也被草酸苷和星皂苷靶向。结论确定了化合物对ait相关途径的作用机制。因此,基于网络药理学的策略将为AIT治疗提供新的见解。然而,需要进一步的研究来验证这项研究,以证明生物活性是治疗AIT的有希望的候选药物。
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引用次数: 0
A Comprehensive Review on Possible Synergistic Therapeutic Effects and Comparison Between Phytochemical and Nutritional Profile of Medicago sativa and Panax ginseng 紫花苜蓿与人参可能协同治疗作用的综合综述及植物化学和营养成分的比较
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-26 DOI: 10.1177/09731296231197306
Sachin Kumar, Ashok Kumar, Suhasini Nayal, Aman Shukla, Shashank Kailkhura
Medicago sativa is the “Father of all herbs” or “King of Herbs,” and Panax ginseng is the “‘Man root” or “Herb for all healings.” Individually, both have copious numbers of phytochemicals and nutrients like flavonoids, saponins, ginsenosides, vitamins, minerals, protein, and so on, and this has already been proven by many scientific studies. This comprehensive review aims to provide an overview of the potential health benefits of M. sativa and P. ginseng as herbs for complete wellness. The review also compares the nutritional profiles of these two herbs and discusses the potential synergistic effects of combining them with some existing scientific evidence. The review highlights the need for further research to validate the efficacy of these herbs as a magical combination for complete wellness and recommends precautions for potential side effects and dosage considerations. Several studies suggest that individually, each herb has various similar clinical significances, like immunomodulating properties, anti-inflammatory properties, antioxidant properties, improved cognitive function, and so on. But in combination, they may show synergistic effects like improved energy and endurance, immune boosters, and cognitive functions. After studying various articles, it is fair to say that both herbs may be considered complete health tonics for complete wellness. Due to limitations and gaps in the current scientific literature, the findings of this review may contribute to further clinical trials and validation of these herbs for improved wellness.
紫花苜蓿是“草药之父”或“草药之王”,人参是“男人的根”或“所有治疗的草药”。单独来说,它们都含有大量的植物化学物质和营养物质,如类黄酮、皂苷、人参皂苷、维生素、矿物质、蛋白质等,这已经被许多科学研究证明了。这篇综合综述的目的是提供一个概述的潜在健康益处的苜蓿和人参作为草药完全健康。这篇综述还比较了这两种草药的营养成分,并讨论了将它们与一些现有的科学证据结合起来的潜在协同效应。这篇综述强调需要进一步的研究来验证这些草药作为一种神奇的健康组合的功效,并建议对潜在的副作用和剂量的注意事项进行预防。几项研究表明,每种草药都有不同的临床意义,如免疫调节特性、抗炎特性、抗氧化特性、改善认知功能等。但结合起来,它们可能会显示出协同效应,比如提高能量和耐力,增强免疫力和认知功能。在研究了各种各样的文章之后,公平地说,这两种草药都可以被认为是完全健康的补品。由于目前科学文献的局限性和空白,本综述的发现可能有助于进一步的临床试验和验证这些草药改善健康。
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引用次数: 0
Bioinformatics, Molecular Docking Simulation and in Vitro Experiments Reveal the Bioactive Compounds and Mechanism of Coptis Chinensis Franch. Against Colorectal Adenocarcinoma 生物信息学、分子对接模拟和体外实验揭示黄连的生物活性成分及其作用机制。抗结直肠腺癌
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-26 DOI: 10.1177/09731296231189553
Xin Liu, Xu-ying Huang, Zhong Liu, Li Liu, Han Tu
Background Coptis chinensis Franch. (CCF) is a Traditional Chinese medicine known for its good anti-cancer effects. However, the bioactive compounds and mechanisms underlying its anti-colorectal adenocarcinoma (COAD) remains unclear. Objectives This study aims to reveal the bioactive compounds and mechanism of CCF against COAD by utilizing bioinformatics, molecular docking simulation and in vitro experiments. Materials and Methods Bioactive compounds and candidate targets of CCF against COAD were collected using the Traditional Chinese Medicine Systems Pharmacology Database, Analysis Platform (TCMSP), Gene Expression Omnibus (GEO), Gene Cards, and SwissTargetPrediction databases, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID (v2022q3) database. The “Compounds-Targets-Pathways” (C-T-P) and “Protein-Protein Interaction” (PPI) networks were constructed using Cytoscape (v3.8.0) to identify the hub targets. AutoDock Vina (v1.2.0), UNLCAN, TCGA, MTT, plate cloning, and quantitative real-time PCR (qPCR) assays were used to confirm the results. Results The “C-T-P” and “PPI” networks revealed three hub targets: checkpoint kinase 1 (CHEK1), polo like kinase 1 (PLK1), and aurora kinase B (AURKB). Molecular docking simulation results showed that berberine, a candidate bioactive compound of CCF, had high affinity with the hub targets, comparable to that of positive drugs. Both CCF ethanol extracts and berberine significantly down-regulated CHEK1, PLK1, and AURKB, inhibited proliferation and promoted apoptosis of HCT-116 cells. Conclusion To summarize, CCF inhibits COAD by down-regulating CHEK1, PLK1, and AURKB, with berberine as its primary bioactive compound.
背景黄连(Coptis chinensis france)。(CCF)是一种具有良好抗癌作用的传统中药。然而,其抗结直肠腺癌(COAD)的生物活性化合物及其机制尚不清楚。本研究旨在通过生物信息学、分子对接模拟和体外实验等手段,揭示CCF抗COAD的活性成分及其作用机制。材料与方法分别利用中药系统药理学数据库(Traditional Chinese system Pharmacology Database)、分析平台(Analysis Platform, TCMSP)、基因表达综合数据库(Gene Expression Omnibus, GEO)、基因卡(Gene Cards)和SwissTargetPrediction数据库收集CCF抗COAD的活性化合物和候选靶点。使用DAVID (v2022q3)数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。利用Cytoscape (v3.8.0)构建“化合物-靶标-通路”(C-T-P)和“蛋白-蛋白相互作用”(PPI)网络,对枢纽靶点进行识别。采用AutoDock v1.2.0、UNLCAN、TCGA、MTT、平板克隆、实时荧光定量PCR (qPCR)等方法对结果进行验证。结果“C-T-P”和“PPI”网络揭示了三个枢纽靶点:检查点激酶1 (CHEK1)、polo样激酶1 (PLK1)和极光激酶B (AURKB)。分子对接模拟结果显示,CCF候选生物活性化合物小檗碱与枢纽靶点具有高亲和力,与阳性药物具有相当的亲和力。CCF乙醇提取物和小檗碱均显著下调CHEK1、PLK1和AURKB,抑制HCT-116细胞增殖,促进细胞凋亡。综上所述,CCF通过下调CHEK1、PLK1和AURKB抑制COAD,其主要活性成分为小檗碱。
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引用次数: 0
Optimization of the Integrated Processing Technology of Primary Processing for Asparagi Radix by HPLC-CAD Combined with the Box-Behnken Design HPLC-CAD结合Box-Behnken设计优化芦笋初加工工艺
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-25 DOI: 10.1177/09731296231191375
Ju Zhang, Bing Wang, Guanglin Zhu, Guo Feng, Wei Li, Hongmei Su, Wenjing Wang, Xie-an Yu, Xueli Song, Zhengyan He
Background Asparagi Radix (AR) is one of the widely used Traditional Chinese Medicines (TCMs) for clinical applications, owning the effects of clearing the lungs and promoting body fluid, nourishing yin, and moistening the lung. To reduce the loss of active ingredients and improve production efficiency, the integrated processing technology of primary processing was used to obtain the decoction pieces of AR. However, there are no specific processing methods and index ingredients of AR in Chinese Pharmacopoeia (2020 edition). Materials and Methods This study aimed to establish a method of content determination of protodioscin and asparagine by high-performance liquid chromatography with charged aerosol detector (HPLC-CAD) as the index of process optimization. Furthermore, Box-Behnken design was used to optimize the integrated processing technology of primary processing. Results The result showed the contents of protodioscin and asparagine could reach 0.2678% and 0.4114%, respectively, both above the traditional process. After verification, the actual value (99.56) and predicted value (101.15) were similar, indicating that the integrated technology was feasible. In particular, the optimized process parameters of boiling time, drying time, and temperature were 25 min, 12 h, and 60°C, respectively. Conclusion In summary, these research findings may provide a reference for the primary processing and quality control of AR.
芦笋是临床应用广泛的中药之一,具有清肺活液、滋阴润肺的作用。为了减少有效成分的损失,提高生产效率,采用初加工一体化加工工艺获得了AR饮片。但《中国药典》(2020年版)中没有具体的AR加工方法和指标成分。材料与方法本研究旨在建立高效液相色谱-带电气溶胶检测器(HPLC-CAD)测定原薯蓣皂苷和天冬酰胺含量的方法,并以此为工艺优化指标。采用Box-Behnken设计对初级加工的综合加工工艺进行了优化。结果原薯蓣皂苷和天冬酰胺的含量分别达到0.2678%和0.4114%,均高于传统工艺。经验证,实际值(99.56)与预测值(101.15)比较接近,表明集成技术是可行的。其中,最优工艺参数沸腾时间为25 min,干燥时间为12 h,温度为60℃。结论本研究结果可为AR的初级加工和质量控制提供参考。
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引用次数: 0
Ponicidin Induces Apoptosis and Inhibits Tumor Growth in C666-1 Nasopharyngeal Cancer Cells poniciidin诱导C666-1鼻咽癌细胞凋亡及抑制肿瘤生长
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-24 DOI: 10.1177/09731296231183277
Yuanfeng Shen, Lu Zhang, Aihui Hou, Kaviya Suresh, Anbarasan Balu, Zhe Gong
Background Nasopharyngeal carcinoma (NPC), predominant in Southern China and Southeast Asia, is a malignant tumor that arises from the epithelial lining of the nasopharynx. Current NPC treatments result in unfavorable side effects. Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic antitumor drugs. Ponicidin, an ent-kaurane diterpenoid, has been demonstrated to possess several pharmacological activities, including antitumor, antibacterial, immunoregulatory, antiviral, and anti-inflammatory properties. Materials and Methods In the current investigation, the anti-carcinogenic activity of Ponicidin against nasopharyngeal cell line C666-1, has been investigated. The influence of Ponicidin on cell viability, apoptotic induction, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and apoptotic markers has been examined. Doxorubicin was selected as the positive control for the experiments. Results The effect of Ponicidin on the viability of C666-1 cells revealed that its cytotoxic potential increased in a dose-dependent pattern and the optimum concentration chosen for further experiments was 7.5 µM. The Ponicidin-treated cells demonstrated a significant increase in the amount of TBARS, whereas it reduced the activity of superoxide dismutase (SOD) and glutathione (GSH) levels, indicating augmented oxidative stress and lower antioxidant activity in the C666-1 cells. The acridine orange/ethidium bromide (AO/EtBr) staining technique was used to assess morphological changes with respect to apoptosis, which confirmed its apoptotic nature. Furthermore, Ponicidin elevated the ROS generation, modified the mitochondrial membrane permeability, elevated the apoptotic marker levels (caspase-3, caspase-9, and Bax) and reduced the Bcl-2 expression in C666-1 cell lines. Conclusion The findings suggest that Ponicidin successfully inhibited cancer cell proliferation by following the mitochondrial apoptotic pathway and thus could be effectively utilized as a potent anti-cancer agent for the treatment of nasopharyngeal cancer.
鼻咽癌(NPC)是一种起源于鼻咽上皮的恶性肿瘤,主要发生在中国南部和东南亚。目前的鼻咽癌治疗导致不良的副作用。具有抗增殖能力的天然化合物作为一种减轻辐射和合成抗肿瘤药物毒性的方法越来越受欢迎。poniciidin是一种正戊烷二萜,已被证明具有多种药理活性,包括抗肿瘤、抗菌、免疫调节、抗病毒和抗炎特性。材料与方法本实验研究了poniciidin对鼻咽癌细胞株C666-1的抗癌作用。研究了Ponicidin对细胞活力、凋亡诱导、线粒体膜电位(MMP)、活性氧(ROS)生成和凋亡标志物的影响。实验选用阿霉素作为阳性对照。结果Ponicidin对C666-1细胞的杀伤作用呈剂量依赖性增加,进一步实验的最佳浓度为7.5µM。ponicidin处理的C666-1细胞显示出TBARS数量显著增加,而超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平降低,表明氧化应激增强,抗氧化活性降低。采用吖啶橙/溴化乙啶(AO/EtBr)染色技术观察细胞凋亡的形态学变化,证实其凋亡性质。此外,Ponicidin增加了C666-1细胞系ROS的生成,改变了线粒体膜的通透性,提高了凋亡标志物(caspase-3、caspase-9和Bax)的水平,降低了Bcl-2的表达。结论Ponicidin通过线粒体凋亡途径成功抑制了鼻咽癌细胞的增殖,可作为鼻咽癌的有效抗癌药物。
{"title":"Ponicidin Induces Apoptosis and Inhibits Tumor Growth in C666-1 Nasopharyngeal Cancer Cells","authors":"Yuanfeng Shen, Lu Zhang, Aihui Hou, Kaviya Suresh, Anbarasan Balu, Zhe Gong","doi":"10.1177/09731296231183277","DOIUrl":"https://doi.org/10.1177/09731296231183277","url":null,"abstract":"Background Nasopharyngeal carcinoma (NPC), predominant in Southern China and Southeast Asia, is a malignant tumor that arises from the epithelial lining of the nasopharynx. Current NPC treatments result in unfavorable side effects. Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic antitumor drugs. Ponicidin, an ent-kaurane diterpenoid, has been demonstrated to possess several pharmacological activities, including antitumor, antibacterial, immunoregulatory, antiviral, and anti-inflammatory properties. Materials and Methods In the current investigation, the anti-carcinogenic activity of Ponicidin against nasopharyngeal cell line C666-1, has been investigated. The influence of Ponicidin on cell viability, apoptotic induction, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and apoptotic markers has been examined. Doxorubicin was selected as the positive control for the experiments. Results The effect of Ponicidin on the viability of C666-1 cells revealed that its cytotoxic potential increased in a dose-dependent pattern and the optimum concentration chosen for further experiments was 7.5 µM. The Ponicidin-treated cells demonstrated a significant increase in the amount of TBARS, whereas it reduced the activity of superoxide dismutase (SOD) and glutathione (GSH) levels, indicating augmented oxidative stress and lower antioxidant activity in the C666-1 cells. The acridine orange/ethidium bromide (AO/EtBr) staining technique was used to assess morphological changes with respect to apoptosis, which confirmed its apoptotic nature. Furthermore, Ponicidin elevated the ROS generation, modified the mitochondrial membrane permeability, elevated the apoptotic marker levels (caspase-3, caspase-9, and Bax) and reduced the Bcl-2 expression in C666-1 cell lines. Conclusion The findings suggest that Ponicidin successfully inhibited cancer cell proliferation by following the mitochondrial apoptotic pathway and thus could be effectively utilized as a potent anti-cancer agent for the treatment of nasopharyngeal cancer.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135925556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Catalpol Ameliorates Myocardial I/R Injury Through PI3k/Akt/P53 Signaling-mediated Anti-autophagy and Anti-apoptosis 梓醇通过PI3k/Akt/P53信号介导的抗自噬和抗凋亡改善心肌I/R损伤
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-24 DOI: 10.1177/09731296231189557
Lingai Hu, Yukun Sun, Hongsheng Zhang, Yong Cao, Jinguo Zhang
Background Myocardial infarction (MI) is a leading cardiovascular disease worldwide, with high mortality. Purpose The study aimed to observe the mechanism of catalpol inhibiting apoptosis and autophagy in H9c2 cells after ischemia/reperfusion (I/R) injury. Materials and Methods We grouped H9c2 cells into 4 groups: control, I/R injury, catalpol (I/R injury +1 ug/mL catalpol treatment), and wortmannin (I/R injury + 1 ug/mL catalpol +150 nM wortmannin treatment) groups. Both catalpol and wortmannin group cells were given drug treatment 30 min before I/R injury. At 2h post-I/R insult, we used flow cytometry for detecting cellular apoptosis and reactive oxygen species (ROS) levels. We identified p-PI3K, p-Akt, PI3K, Akt, p53, Bcl-2, Caspase-3, Bax, beclin1, LC3II, and LC3I protein expression levels. Results I/R significantly increased the apoptosis rate and ROS level of H9c2 cells, increased expression levels of p53, LC3II/LC3I, and Caspase-3, and decreased p-Akt/Akt, beclin1, Bcl-2/Bax, and p-PI3K/PI3K expression levels. Catalpol can reduce the expressions of p53, Caspase-3, and LC3II/LC3I (p < 0.5). Catalpol can increase the expression levels of Akt/ p-Akt, Bax/ Bcl-2, and beclin1. Also, it can inhibit apoptosis and autophagy levels of H9c2 cells (p < 0.5). Wortmannin, a PI3 K-specific inhibitor, was able partially to block the catalpol’s and anti-autophagic and anti-apoptotic effects. Conclusion Catalpol can inhibit apoptosis, reduces excessive autophagy, and alleviates the effects of myocardial ischemia-reperfusion through PI3K/Akt/p53 pathway.
背景心肌梗死(MI)是世界范围内主要的心血管疾病,死亡率高。目的观察梓醇抑制缺血再灌注(I/R)损伤后H9c2细胞凋亡和自噬的作用机制。材料与方法将H9c2细胞分为4组:对照组、I/R损伤组、梓醇组(I/R损伤+1 ug/mL梓醇处理)、wortmannin组(I/R损伤+1 ug/mL梓醇+150 nM wortmannin处理)。梓醇组和沃特曼宁组细胞均在I/R损伤前30 min给予药物治疗。在i /R损伤后2h,我们用流式细胞术检测细胞凋亡和活性氧(ROS)水平。我们检测了p-PI3K、p-Akt、PI3K、Akt、p53、Bcl-2、Caspase-3、Bax、beclin1、LC3II和LC3I蛋白的表达水平。结果I/R显著提高H9c2细胞的凋亡率和ROS水平,提高p53、LC3II/LC3I、Caspase-3的表达水平,降低p-Akt/Akt、beclin1、Bcl-2/Bax、p-PI3K/PI3K的表达水平。梓醇可降低p53、Caspase-3、LC3II/LC3I的表达(p <0.5)。Catalpol可上调Akt/ p-Akt、Bax/ Bcl-2、beclin1的表达水平。它还能抑制H9c2细胞的凋亡和自噬水平(p <0.5)。pi3k特异性抑制剂Wortmannin能够部分阻断梓醇的抗自噬和抗凋亡作用。结论梓醇可通过PI3K/Akt/p53通路抑制细胞凋亡,减少过度自噬,减轻心肌缺血-再灌注的影响。
{"title":"Catalpol Ameliorates Myocardial I/R Injury Through PI3k/Akt/P53 Signaling-mediated Anti-autophagy and Anti-apoptosis","authors":"Lingai Hu, Yukun Sun, Hongsheng Zhang, Yong Cao, Jinguo Zhang","doi":"10.1177/09731296231189557","DOIUrl":"https://doi.org/10.1177/09731296231189557","url":null,"abstract":"Background Myocardial infarction (MI) is a leading cardiovascular disease worldwide, with high mortality. Purpose The study aimed to observe the mechanism of catalpol inhibiting apoptosis and autophagy in H9c2 cells after ischemia/reperfusion (I/R) injury. Materials and Methods We grouped H9c2 cells into 4 groups: control, I/R injury, catalpol (I/R injury +1 ug/mL catalpol treatment), and wortmannin (I/R injury + 1 ug/mL catalpol +150 nM wortmannin treatment) groups. Both catalpol and wortmannin group cells were given drug treatment 30 min before I/R injury. At 2h post-I/R insult, we used flow cytometry for detecting cellular apoptosis and reactive oxygen species (ROS) levels. We identified p-PI3K, p-Akt, PI3K, Akt, p53, Bcl-2, Caspase-3, Bax, beclin1, LC3II, and LC3I protein expression levels. Results I/R significantly increased the apoptosis rate and ROS level of H9c2 cells, increased expression levels of p53, LC3II/LC3I, and Caspase-3, and decreased p-Akt/Akt, beclin1, Bcl-2/Bax, and p-PI3K/PI3K expression levels. Catalpol can reduce the expressions of p53, Caspase-3, and LC3II/LC3I (p < 0.5). Catalpol can increase the expression levels of Akt/ p-Akt, Bax/ Bcl-2, and beclin1. Also, it can inhibit apoptosis and autophagy levels of H9c2 cells (p < 0.5). Wortmannin, a PI3 K-specific inhibitor, was able partially to block the catalpol’s and anti-autophagic and anti-apoptotic effects. Conclusion Catalpol can inhibit apoptosis, reduces excessive autophagy, and alleviates the effects of myocardial ischemia-reperfusion through PI3K/Akt/p53 pathway.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135926303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Schefflera arboricola Tablets Relieve Diabetic Neuropathic Pain: Involvement of Oxidative Stress and Inflammation 雪弗勒草片减轻糖尿病神经性疼痛:氧化应激和炎症的参与
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-22 DOI: 10.1177/09731296231193801
Shaomei Lin, Yunzhu Shen, Xiaowei Huang, Shifeng Lin, Xiaoning Shi
Background Diabetic neuropathic pain (DNP) is a serious chronic complication of diabetes mellitus. Oxidative stress and inflammation are considered the central mechanisms of its pathogenesis. Schefflera arboricola (SA) is a Schefflera plant of the Araliaceae family that has the effect of pain relief. In this study, the effect of SA on DNP was first investigated. Materials and Methods Diabetic neuropathy in rats was induced by a single injection of streptozotocin (60 mg/kg). Three weeks later, SA (100 mg/kg, 300 mg/kg) or gabapentin (100 mg/kg) was given once a day for a week. Blood glucose, body weight, and thermal withdrawal latency in DNP rats were measured. The morphology of the sciatic nerve was observed by light microscopy and toluidine blue staining. Semiquantitative analysis of myelin basic protein (MBP) of the sciatic nerve was performed by immunohistochemistry. IL-1β, tumor necrosis factor-alpha (TNF-α), and IL-6 were detected by enzyme-linked immunosorbent assay. Commercial reagent kits were used to detect inducible nitric oxide synthase, superoxide dismutase (SOD), and malondialdehyde (MDA). The expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) were detected by Western blot. Results DNP rat model was successfully constructed. SA and gabapentin could alleviate the thermal sting pain of DNP rats, increase the expression of MBP and SOD, and decrease the expression of proinflammatory agents and MDA. Moreover, SA could reverse the upregulation of NF-κB and the downregulation of Nrf2. Conclusion SA has a significant protective effect on DNP, manifesting in the improvement of allodynia and sciatic nerve pathology, inhibition of neuroinflammation, reduction of oxidative stress, enhancement of Nrf2, and inhibition of NF-κB.
背景:糖尿病神经性疼痛(DNP)是糖尿病的严重慢性并发症。氧化应激和炎症被认为是其发病的主要机制。雪弗勒树(SA)是一种雪弗勒属五重子科植物,具有镇痛作用。本研究首次探讨了SA对DNP的影响。材料与方法单次注射链脲佐菌素(60 mg/kg)诱导大鼠糖尿病性神经病变。3周后给予SA (100 mg/kg、300 mg/kg)或加巴喷丁(100 mg/kg),每天1次,连续1周。测定DNP大鼠的血糖、体重和热戒断潜伏期。光镜下观察坐骨神经形态,甲苯胺蓝染色。免疫组化半定量分析坐骨神经髓鞘碱性蛋白(MBP)。采用酶联免疫吸附法检测IL-1β、肿瘤坏死因子α (TNF-α)和IL-6。采用商业试剂盒检测诱导型一氧化氮合酶、超氧化物歧化酶(SOD)和丙二醛(MDA)。Western blot检测核因子-红细胞2相关因子2 (Nrf2)和核因子-κB (NF-κB)的表达水平。结果成功构建DNP大鼠模型。SA和加巴喷丁能减轻DNP大鼠的热刺痛,提高MBP和SOD的表达,降低促炎剂和MDA的表达。此外,SA可以逆转NF-κB的上调和Nrf2的下调。结论SA对DNP具有明显的保护作用,表现为改善异位性痛和坐骨神经病理,抑制神经炎症,降低氧化应激,增强Nrf2,抑制NF-κB。
{"title":"<i>Schefflera arboricola</i> Tablets Relieve Diabetic Neuropathic Pain: Involvement of Oxidative Stress and Inflammation","authors":"Shaomei Lin, Yunzhu Shen, Xiaowei Huang, Shifeng Lin, Xiaoning Shi","doi":"10.1177/09731296231193801","DOIUrl":"https://doi.org/10.1177/09731296231193801","url":null,"abstract":"Background Diabetic neuropathic pain (DNP) is a serious chronic complication of diabetes mellitus. Oxidative stress and inflammation are considered the central mechanisms of its pathogenesis. Schefflera arboricola (SA) is a Schefflera plant of the Araliaceae family that has the effect of pain relief. In this study, the effect of SA on DNP was first investigated. Materials and Methods Diabetic neuropathy in rats was induced by a single injection of streptozotocin (60 mg/kg). Three weeks later, SA (100 mg/kg, 300 mg/kg) or gabapentin (100 mg/kg) was given once a day for a week. Blood glucose, body weight, and thermal withdrawal latency in DNP rats were measured. The morphology of the sciatic nerve was observed by light microscopy and toluidine blue staining. Semiquantitative analysis of myelin basic protein (MBP) of the sciatic nerve was performed by immunohistochemistry. IL-1β, tumor necrosis factor-alpha (TNF-α), and IL-6 were detected by enzyme-linked immunosorbent assay. Commercial reagent kits were used to detect inducible nitric oxide synthase, superoxide dismutase (SOD), and malondialdehyde (MDA). The expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) were detected by Western blot. Results DNP rat model was successfully constructed. SA and gabapentin could alleviate the thermal sting pain of DNP rats, increase the expression of MBP and SOD, and decrease the expression of proinflammatory agents and MDA. Moreover, SA could reverse the upregulation of NF-κB and the downregulation of Nrf2. Conclusion SA has a significant protective effect on DNP, manifesting in the improvement of allodynia and sciatic nerve pathology, inhibition of neuroinflammation, reduction of oxidative stress, enhancement of Nrf2, and inhibition of NF-κB.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"87 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apigenin-induced Apoptosis is Reduced via Endoplasmic Reticulum Stress and ATF6/PERK Signaling in Human Gastric Cancer Cells 芹菜素诱导的胃癌细胞凋亡通过内质网应激和ATF6/PERK信号通路减少
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-22 DOI: 10.1177/09731296231188792
Cuizhu Zhuo, Xiaolin Wang, Yun Li, Yongmei Tang, Manman Wang, Liying Hou
Background Apigenin effectively inhibits the growth of human gastric carcinoma SGC-7901 cells and induces apoptosis as well. This study investigated the effects of ATF6 and PERK signaling pathways in unfolded protein response (UPR) and endoplasmic reticulum stress (ERS) on the apoptosis induced by apigenin in human gastric carcinoma SGC-7901 cells. Materials and Methods SGC-7901 cells were cultured with apigenin and tunicamycin for 48 h or with apigenin for 12–48 h. CCK-8 was used to determine cell viability. The mRNA expression level was detected by RT-qPCR. The expression of related proteins was explored by Western blot. The apoptosis rate of cells and cell-cycle arrest were evaluated by flow cytometer. Results The results of CCK-8 confirmed that apigenin could induce apoptosis of SGC-7901 cells. In the apigenin-treated cells group, the protein and mRNA levels of GRP78 and GRP94 dose- and time-dependently increased. Additionally, apigenin-activated UPR components PERK and ATF6. However, apigenin exerted no influence on CHOP expression or JNK activation. Pretreatment with 4-PBA significantly increased the apigenin-triggered apoptosis in SCG-7901 cells ( p < 0.05). Conclusion The results revealed the protective effect of UPR performance on apigenin-triggered apoptosis in SGC-7901 cells.
芹菜素能有效抑制人胃癌SGC-7901细胞的生长,诱导细胞凋亡。本研究探讨了未折叠蛋白反应(UPR)和内质网应激(ERS)中ATF6和PERK信号通路对芹菜素诱导的人胃癌SGC-7901细胞凋亡的影响。材料与方法SGC-7901细胞分别与芹菜素和tunicamycin联合培养48 h或与芹菜素联合培养12-48 h, CCK-8检测细胞活力。RT-qPCR检测mRNA表达水平。Western blot检测相关蛋白的表达。流式细胞仪检测细胞凋亡率和细胞周期阻滞。结果CCK-8检测结果证实芹菜素可诱导SGC-7901细胞凋亡。在芹菜素处理的细胞组中,GRP78和GRP94的蛋白和mRNA水平呈剂量和时间依赖性升高。此外,芹菜素激活UPR成分PERK和ATF6。然而,芹菜素对CHOP表达和JNK激活没有影响。4-PBA预处理显著增加芹菜素引发的SCG-7901细胞凋亡(p <0.05)。结论UPR对芹菜素诱发的SGC-7901细胞凋亡具有保护作用。
{"title":"<i>Apigenin</i>-induced Apoptosis is Reduced via Endoplasmic Reticulum Stress and ATF6/PERK Signaling in Human Gastric Cancer Cells","authors":"Cuizhu Zhuo, Xiaolin Wang, Yun Li, Yongmei Tang, Manman Wang, Liying Hou","doi":"10.1177/09731296231188792","DOIUrl":"https://doi.org/10.1177/09731296231188792","url":null,"abstract":"Background Apigenin effectively inhibits the growth of human gastric carcinoma SGC-7901 cells and induces apoptosis as well. This study investigated the effects of ATF6 and PERK signaling pathways in unfolded protein response (UPR) and endoplasmic reticulum stress (ERS) on the apoptosis induced by apigenin in human gastric carcinoma SGC-7901 cells. Materials and Methods SGC-7901 cells were cultured with apigenin and tunicamycin for 48 h or with apigenin for 12–48 h. CCK-8 was used to determine cell viability. The mRNA expression level was detected by RT-qPCR. The expression of related proteins was explored by Western blot. The apoptosis rate of cells and cell-cycle arrest were evaluated by flow cytometer. Results The results of CCK-8 confirmed that apigenin could induce apoptosis of SGC-7901 cells. In the apigenin-treated cells group, the protein and mRNA levels of GRP78 and GRP94 dose- and time-dependently increased. Additionally, apigenin-activated UPR components PERK and ATF6. However, apigenin exerted no influence on CHOP expression or JNK activation. Pretreatment with 4-PBA significantly increased the apigenin-triggered apoptosis in SCG-7901 cells ( p < 0.05). Conclusion The results revealed the protective effect of UPR performance on apigenin-triggered apoptosis in SGC-7901 cells.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136011509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Mechanisms of Herba Epimedii in Lung Cancer Treatment: A Combination of Molecular Docking and Network Pharmacology Analyses 淫羊藿治疗肺癌的机制:分子对接与网络药理学分析的结合
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-19 DOI: 10.1177/09731296231189095
Jinhua Zhang
Introduction Lung cancer (LC) ranks among the most prevalent malignant neoplasms globally. As a Traditional Chinese medicine (TCM), Herba Epimedii has been commonly used for treating LC. However, the specific mechanism of LC remains to be elucidated. Objectives This research aimed to explore the mechanisms of Herba Epimedii in treating LC according to molecular docking and network pharmacology. Materials and Methods The active components (ACs) and targets of Herba Epimedii were screened through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. LC targets were retrieved from GeneCards and DisGeNET databases. Cytoscape v3.9.0 was employed to construct a “drug-component-disease-target” network. The STRING database and Cytoscape 3.9.0 software were utilized to establish a PPI network. The DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The AutoDock software was employed for molecular docking verification, and the Pymol software was applied for visual processing. Results Herba Epimedii acted on 108 LC treatment targets through 22 ACs. Five core components were screened, including quercetin, luteolin, kaempferol, anhydroicaritin, and 8-isopentenyl-kaempferol, while 12 core targets were screened, including TP53, AKT1, MYC, CASP3, ESR1, JUN, HIF1A, VEGFA, TNF, CCND1, EGFR, and IL-6. GO enrichment analysis mainly involved positive regulation of gene expression, positive regulation of the apoptotic process, enzyme binding, identical protein binding, macromolecular complex, nucleoplasm, etc. KEGG enrichment analysis mainly involved p53, interleukin-17, PI3K-Akt, and other signaling pathways. Five core components all demonstrated excellent binding activities with the core targets. Conclusion The mechanisms of Herba Epimedii in LC treatment may involve multiple components, targets, and pathways, inducing apoptosis, and inhibiting proliferation, invasion, metastasis, and drug resistance of LC cells.
肺癌(LC)是全球最常见的恶性肿瘤之一。淫羊藿作为一种中药,被广泛用于治疗LC。然而,LC的具体机制仍有待阐明。目的从分子对接和网络药理学角度探讨淫羊藿治疗LC的作用机制。材料与方法通过中药系统药理学(TCMSP)数据库筛选淫羊藿的有效成分和靶点。LC目标从GeneCards和DisGeNET数据库中检索。采用Cytoscape v3.9.0构建“药物-组分-疾病-靶点”网络。利用STRING数据库和Cytoscape 3.9.0软件建立PPI网络。DAVID数据库用于基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。采用AutoDock软件进行分子对接验证,采用Pymol软件进行可视化处理。结果淫羊藿通过22个ac对108个LC治疗靶点起作用。筛选5个核心成分,包括槲皮素、木檀素、山奈酚、无氢羊藿苷、8-异戊基山奈酚,筛选12个核心靶点,包括TP53、AKT1、MYC、CASP3、ESR1、JUN、HIF1A、VEGFA、TNF、CCND1、EGFR、IL-6。氧化石墨烯富集分析主要涉及基因表达的正调控、凋亡过程的正调控、酶结合、同蛋白结合、大分子复合物、核质等。KEGG富集分析主要涉及p53、白介素-17、PI3K-Akt等信号通路。5个核心组分与核心靶点均表现出良好的结合活性。结论淫羊藿治疗LC的机制可能涉及多种成分、靶点和途径,可诱导凋亡,抑制LC细胞的增殖、侵袭、转移和耐药。
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Induction of Apoptosis by Cynaropicrin in Human Colon Cancer Cell Line HCT-116 through the Mitochondria-mediated Apoptotic Pathway Cynaropicrin通过线粒体介导的凋亡途径诱导人结肠癌细胞系HCT-116凋亡
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-13 DOI: 10.1177/09731296231183833
Lei Wang, Xiaoqin Bie, Suresh Mickymaray, Abdulaziz S. Alothaim, Yan Pei, Huaping Gong
Background Colon cancer continues to be the third most commonly occurring cancer around the globe with both lifestyle-related risk factors and genetic dispositions. Owing to the increased incidence of the disease, there is a need to find new treatment options which are easily accessible and less toxic to the cells. Cynaropicrin, a sesquiterpene extract from the artichoke plant exhibits varied properties such as anti-inflammatory, anti-cancer, and antioxidant among others. In the current investigation, the anti-cancer potential of the cynaropicrin extract was observed against colon cancer in HCT-116 cell lines. Materials and Methods The drug exhibited a considerable decrease in cell proliferation. Also analyzed was the reactive oxygen species (ROS) generation and apoptosis induction by cynaropicrin on the HCT-116 cell line. The AO/EtBr staining confirmed the apoptotic induction through chromatin condensation by fluorescence microscopic examination followed by DAPI staining of the treated HCT-116 cells which showed nuclear condensation and disintegration. Results Furthermore, it was observed that cynaropicrin elevated the levels of ROS in the cells which modified the mitochondrial membrane permeability in the HCT-116 cell lines. The study also evaluated the levels of apoptotic proteins and the expression of inflammatory cytokines concerning cells treated with cynaropicrin and untreated control cells. Conclusion It has been observed that cynaropicrin treatment can lead to apoptosis in the HCT-116 cell line via mitochondria-mediated apoptotic pathway and if further evaluated, it can turn out to be a potent anti-cancer drug for effective management of colon cancer.
结肠癌仍然是全球第三大常见癌症,与生活方式相关的风险因素和遗传倾向有关。由于该病发病率增加,有必要寻找易于获得且对细胞毒性较小的新治疗办法。Cynaropicrin是一种从朝鲜蓟植物中提取的倍半萜素,具有多种特性,如抗炎、抗癌和抗氧化等。本研究在HCT-116细胞系中观察了苦辛酸提取物对结肠癌的抗癌作用。材料与方法该药物能显著抑制细胞增殖。并分析了cynaropicrin对HCT-116细胞株的活性氧(ROS)生成及诱导凋亡的作用。AO/EtBr染色证实HCT-116细胞通过荧光显微镜观察染色质凝集诱导凋亡,DAPI染色显示细胞核凝集和解体。结果cynaropicrin可提高细胞内ROS水平,改变HCT-116细胞系线粒体膜通透性。该研究还评估了cynaropicrin处理的细胞和未处理的对照细胞的凋亡蛋白水平和炎症细胞因子的表达。结论cynaropicrin可通过线粒体介导的凋亡途径导致HCT-116细胞凋亡,如果进一步研究,cynaropicrin可能成为一种有效治疗结肠癌的有效抗癌药物。
{"title":"Induction of Apoptosis by Cynaropicrin in Human Colon Cancer Cell Line HCT-116 through the Mitochondria-mediated Apoptotic Pathway","authors":"Lei Wang, Xiaoqin Bie, Suresh Mickymaray, Abdulaziz S. Alothaim, Yan Pei, Huaping Gong","doi":"10.1177/09731296231183833","DOIUrl":"https://doi.org/10.1177/09731296231183833","url":null,"abstract":"Background Colon cancer continues to be the third most commonly occurring cancer around the globe with both lifestyle-related risk factors and genetic dispositions. Owing to the increased incidence of the disease, there is a need to find new treatment options which are easily accessible and less toxic to the cells. Cynaropicrin, a sesquiterpene extract from the artichoke plant exhibits varied properties such as anti-inflammatory, anti-cancer, and antioxidant among others. In the current investigation, the anti-cancer potential of the cynaropicrin extract was observed against colon cancer in HCT-116 cell lines. Materials and Methods The drug exhibited a considerable decrease in cell proliferation. Also analyzed was the reactive oxygen species (ROS) generation and apoptosis induction by cynaropicrin on the HCT-116 cell line. The AO/EtBr staining confirmed the apoptotic induction through chromatin condensation by fluorescence microscopic examination followed by DAPI staining of the treated HCT-116 cells which showed nuclear condensation and disintegration. Results Furthermore, it was observed that cynaropicrin elevated the levels of ROS in the cells which modified the mitochondrial membrane permeability in the HCT-116 cell lines. The study also evaluated the levels of apoptotic proteins and the expression of inflammatory cytokines concerning cells treated with cynaropicrin and untreated control cells. Conclusion It has been observed that cynaropicrin treatment can lead to apoptosis in the HCT-116 cell line via mitochondria-mediated apoptotic pathway and if further evaluated, it can turn out to be a potent anti-cancer drug for effective management of colon cancer.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135740704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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