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.
{"title":"Network Pharmacology-based Analysis to Investigate Bioactive from the Root of <i>Astragalus membranaceus</i> against Immunomodulatory Protein and their Role in Autoimmune Thyroiditis (AIT)","authors":"Yi Wen, Changda Li, Yifan Zeng, Chanyuan Zhou, Qiang Zhang, Tianshu Gao","doi":"10.1177/09731296231189561","DOIUrl":"https://doi.org/10.1177/09731296231189561","url":null,"abstract":"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.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134957988","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}
Pub Date : 2023-09-26DOI: 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.
{"title":"A Comprehensive Review on Possible Synergistic Therapeutic Effects and Comparison Between Phytochemical and Nutritional Profile of <i>Medicago sativa</i> and <i>Panax ginseng</i>","authors":"Sachin Kumar, Ashok Kumar, Suhasini Nayal, Aman Shukla, Shashank Kailkhura","doi":"10.1177/09731296231197306","DOIUrl":"https://doi.org/10.1177/09731296231197306","url":null,"abstract":"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.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134958481","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}
Pub Date : 2023-09-26DOI: 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。
{"title":"Bioinformatics, Molecular Docking Simulation and <i>in Vitro</i> Experiments Reveal the Bioactive Compounds and Mechanism of <i>Coptis Chinensis</i> Franch. Against Colorectal Adenocarcinoma","authors":"Xin Liu, Xu-ying Huang, Zhong Liu, Li Liu, Han Tu","doi":"10.1177/09731296231189553","DOIUrl":"https://doi.org/10.1177/09731296231189553","url":null,"abstract":"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.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134958618","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}
Pub Date : 2023-09-25DOI: 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.
{"title":"Optimization of the Integrated Processing Technology of Primary Processing for <i>Asparagi Radix</i> by HPLC-CAD Combined with the Box-Behnken Design","authors":"Ju Zhang, Bing Wang, Guanglin Zhu, Guo Feng, Wei Li, Hongmei Su, Wenjing Wang, Xie-an Yu, Xueli Song, Zhengyan He","doi":"10.1177/09731296231191375","DOIUrl":"https://doi.org/10.1177/09731296231191375","url":null,"abstract":"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.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135817755","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}
Pub Date : 2023-09-24DOI: 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.
{"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}
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.
{"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}
Pub Date : 2023-09-22DOI: 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.
{"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}
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.
{"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}
Pub Date : 2023-09-19DOI: 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.
{"title":"Mechanisms of <i>Herba Epimedii</i> in Lung Cancer Treatment: A Combination of Molecular Docking and Network Pharmacology Analyses","authors":"Jinhua Zhang","doi":"10.1177/09731296231189095","DOIUrl":"https://doi.org/10.1177/09731296231189095","url":null,"abstract":"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.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"169 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135013983","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}
Pub Date : 2023-09-13DOI: 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.
{"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}