Pub Date : 2023-06-23DOI: 10.1177/09731296231177492
H. Makki, K. Chandrasekharaiah
Biosynthesized copper nanoparticles (CuNPs) are eco-friendly, cost-effective, and biocompatible agents reported for extensive biomedical and bioengineering applications. Different chemical synthesis approaches have been established recently, with challenges of higher toxicity and high cost involved in the synthesis process. Green synthesized nanoparticles emerged and was extensively reported to address the challenges faced by traditional chemical synthesis processes. However, the high toxicity remains a significant challenge for translating the green synthesized nanoparticles into clinically valuable products. To synthesize, characterize, and evaluate the citrus extract-based CuNps cytotoxicity against JURKAT cell lines. An aqueous extract of the citrus fruit was used as a reducing agent, and the CuNps were synthesized. Fourier Transform Infra-Red (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), Ultraviolet-visible (UV-Vis) spectrophotometry, and X-ray diffraction (XRD) were used to confirm the synthesis of CuNp and its structure. Furthermore, the effect of CuNPs on cell viability and toxicity was evaluated by mitochondrial toxicity tests (MTT) and LDH assays against the JURKAT cell lines. The synthesized nanoparticle’s size ranged from 40 to 70 nm, as confirmed through nanoparticle tracking analysis (NTA) and SEM. The synthesized nanoparticles were confirmed to be anti-proliferative with a high percent of cytotoxicity as found from MTT and LDH leakage assays. The size and shape of the synthesized CuNPs as studied by SEM were found to be 30–70 nm and more or less spherical. MTT reported 64.87% inhibition at 320 µg/mL with an IC50 value of 80.78 µg/mL ( p < 0.05). Cytotoxicity as measured by the LDH assay was found to be 53.12 ± 0.89% at 320 µg/mL with an IC50 of 23.12 ± 0.39 when compared to the positive control (11.21 ± 0.15 µg/mL). Green-synthesized CuNPs exhibited potential anticancerous activity in JURKAT cell lines, as evidenced by the LDH and MTT assays.
{"title":"Synthesis and Characterization of Citrus limonum Copper Nanoparticles and Its In Vitro Evaluation of Cytotoxicity Against JURKAT Cells","authors":"H. Makki, K. Chandrasekharaiah","doi":"10.1177/09731296231177492","DOIUrl":"https://doi.org/10.1177/09731296231177492","url":null,"abstract":"Biosynthesized copper nanoparticles (CuNPs) are eco-friendly, cost-effective, and biocompatible agents reported for extensive biomedical and bioengineering applications. Different chemical synthesis approaches have been established recently, with challenges of higher toxicity and high cost involved in the synthesis process. Green synthesized nanoparticles emerged and was extensively reported to address the challenges faced by traditional chemical synthesis processes. However, the high toxicity remains a significant challenge for translating the green synthesized nanoparticles into clinically valuable products. To synthesize, characterize, and evaluate the citrus extract-based CuNps cytotoxicity against JURKAT cell lines. An aqueous extract of the citrus fruit was used as a reducing agent, and the CuNps were synthesized. Fourier Transform Infra-Red (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), Ultraviolet-visible (UV-Vis) spectrophotometry, and X-ray diffraction (XRD) were used to confirm the synthesis of CuNp and its structure. Furthermore, the effect of CuNPs on cell viability and toxicity was evaluated by mitochondrial toxicity tests (MTT) and LDH assays against the JURKAT cell lines. The synthesized nanoparticle’s size ranged from 40 to 70 nm, as confirmed through nanoparticle tracking analysis (NTA) and SEM. The synthesized nanoparticles were confirmed to be anti-proliferative with a high percent of cytotoxicity as found from MTT and LDH leakage assays. The size and shape of the synthesized CuNPs as studied by SEM were found to be 30–70 nm and more or less spherical. MTT reported 64.87% inhibition at 320 µg/mL with an IC50 value of 80.78 µg/mL ( p < 0.05). Cytotoxicity as measured by the LDH assay was found to be 53.12 ± 0.89% at 320 µg/mL with an IC50 of 23.12 ± 0.39 when compared to the positive control (11.21 ± 0.15 µg/mL). Green-synthesized CuNPs exhibited potential anticancerous activity in JURKAT cell lines, as evidenced by the LDH and MTT assays.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":" ","pages":""},"PeriodicalIF":0.7,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42258371","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}
Ferroptosis is a novel type of regulated cell death and targeting ferroptosis may be a potential treatment strategy for lung cancer. Ziyuglycoside II (ZYG II) has a significant inhibitory effect on the growth of lung cancer cells. However, the selective anti-tumor effect of the ZYG II against lung cancer has not been systemically studied. We combined ferrostatin-1 and erastin to explore the potential therapeutic mechanism of the ZYG II for lung adenocarcinoma. A549 and H1299 cells were randomly divided into the control, ZYG II, ferroptosis inhibitor group (ZYG II+ ferrostatin-1), and erastin group (ZYG II+ erastin). Cell proliferation was detected using the CCK-8 method. Cell migration and invasion were evaluated using the Transwell assay. The protein expression levels of Glutathione Peroxidase 4 (GPX4), Solute Carrier Family 7 Member 11 (SLC7A11), and Transferrin receptor 1 (TFR1) were measured using western blotting. Compared with the control group, the cell proliferation, migration, and invasion abilities of the ZYG II group significantly decreased, the protein expression levels of GPX4 and SLC7A11 in the ZYG II group declined significantly, and the expression of TFR1 increased significantly ( p < 0.05). After adding ferrostatin 1 (ZYG II+ Ferrostatin 1), the cell proliferation, migration, and invasion abilities of the inhibited cells were significantly increased, the expression of GPX4 and SLC7A11 increased significantly and the expression of TFR1 decreased significantly ( p < 0.05). However, after adding the erastin (ZYG II+ erastin), the cell viability was further inhibited in A549, the expression levels of GPX4 and SLC7A11 were further inhibited and the expression of TFR1 was further increased ( p < 0.05). ZYG II significantly inhibited the survival rate, proliferation, migration, and invasion ability of A549 and H1299 cells, possibly by inducing ferroptosis.
{"title":"Mechanism of Ziyuglycoside II-mediated Ferroptosis-related Proteins on the Proliferation and Metastasis of Human Lung Adenocarcinoma Cell Lines","authors":"Jian-Hui Zhang, Lijuan Xie, Han-Lu Wang, Hui Chen, Xiao-Rong Meng, Xing Lin, Xin-fu Lin, L. Liao, Ting Chen, Jie-wei Luo, Lu-yu Hong, Xin Chen","doi":"10.1177/09731296231169588","DOIUrl":"https://doi.org/10.1177/09731296231169588","url":null,"abstract":"Ferroptosis is a novel type of regulated cell death and targeting ferroptosis may be a potential treatment strategy for lung cancer. Ziyuglycoside II (ZYG II) has a significant inhibitory effect on the growth of lung cancer cells. However, the selective anti-tumor effect of the ZYG II against lung cancer has not been systemically studied. We combined ferrostatin-1 and erastin to explore the potential therapeutic mechanism of the ZYG II for lung adenocarcinoma. A549 and H1299 cells were randomly divided into the control, ZYG II, ferroptosis inhibitor group (ZYG II+ ferrostatin-1), and erastin group (ZYG II+ erastin). Cell proliferation was detected using the CCK-8 method. Cell migration and invasion were evaluated using the Transwell assay. The protein expression levels of Glutathione Peroxidase 4 (GPX4), Solute Carrier Family 7 Member 11 (SLC7A11), and Transferrin receptor 1 (TFR1) were measured using western blotting. Compared with the control group, the cell proliferation, migration, and invasion abilities of the ZYG II group significantly decreased, the protein expression levels of GPX4 and SLC7A11 in the ZYG II group declined significantly, and the expression of TFR1 increased significantly ( p < 0.05). After adding ferrostatin 1 (ZYG II+ Ferrostatin 1), the cell proliferation, migration, and invasion abilities of the inhibited cells were significantly increased, the expression of GPX4 and SLC7A11 increased significantly and the expression of TFR1 decreased significantly ( p < 0.05). However, after adding the erastin (ZYG II+ erastin), the cell viability was further inhibited in A549, the expression levels of GPX4 and SLC7A11 were further inhibited and the expression of TFR1 was further increased ( p < 0.05). ZYG II significantly inhibited the survival rate, proliferation, migration, and invasion ability of A549 and H1299 cells, possibly by inducing ferroptosis.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"1 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41380072","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 Ziziphi spinosae semen (ZSS), dry mature seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H.F. Chow., are widely used in the treatment of insomnia, fright palpitations, and profuse dreaming in medical treatments. The counterfeit species of ZSS, Ziziphi mauritianae semen (ZMS), and Hovenia dulcis Thunb (HDT) are seeds from Ziziphus incurva Roxb. and Hovenia acerba Lindl., respectively. However, the pharmacopeia is not recorded for ZMS and HDT. In this article, we reviewed the identification methods of ZSS, ZMS, and HDT. Materials and Methods The random amplified polymorphic DNA (RAPD) technique was used to identify the ZSS and its copies. Plant genome DNA was extracted from Z. jujuba Mill., Z. incurva Roxb., and H. acerba Lindl. Random primers were designed to amplify the genome. The amplified products were detected by agarose gel electrophoresis. Results By analyzing the polymorphism of the amplified product DNA fragment, the DNA fingerprint maps of Z. jujuba Mill., Z. incurva Roxb., and H. acerba Lindl. were successfully constructed.
背景酸枣精液（ZSS）是酸枣的干燥成熟种子。变种spinosa（Bunge）Hu ex H.F.Chow。，广泛用于治疗失眠、心悸和多梦的医学治疗。ZSS、酸枣子精液（ZMS）和枳壳子（HDT）的伪品是来自入侵酸枣的种子。和Hovenia acerba Lindl。，分别地然而，药典中没有ZMS和HDT的记录。本文综述了ZSS、ZMS和HDT的鉴定方法。材料与方法采用随机扩增多态性DNA（RAPD）技术对ZSS及其拷贝进行鉴定。植物基因组DNA从Z.jujuba Mill。，Z.inciva Roxb。，和H.acerba Lindl。设计了随机引物来扩增基因组。琼脂糖凝胶电泳检测扩增产物。结果通过对扩增产物DNA片段的多态性分析。，Z.inciva Roxb。，和H.acerba Lindl。成功建造。
{"title":"Identification of Ziziphi Spinosae Semen from its Adulterants Based on RAPD","authors":"Fu-Long Xia, Hong-Wei Cao, Li-Xia Gao, Qing-Kong, Mei-Li, Chuan-jie Wang, Yang-Niu","doi":"10.1177/09731296231171216","DOIUrl":"https://doi.org/10.1177/09731296231171216","url":null,"abstract":"Background Ziziphi spinosae semen (ZSS), dry mature seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H.F. Chow., are widely used in the treatment of insomnia, fright palpitations, and profuse dreaming in medical treatments. The counterfeit species of ZSS, Ziziphi mauritianae semen (ZMS), and Hovenia dulcis Thunb (HDT) are seeds from Ziziphus incurva Roxb. and Hovenia acerba Lindl., respectively. However, the pharmacopeia is not recorded for ZMS and HDT. In this article, we reviewed the identification methods of ZSS, ZMS, and HDT. Materials and Methods The random amplified polymorphic DNA (RAPD) technique was used to identify the ZSS and its copies. Plant genome DNA was extracted from Z. jujuba Mill., Z. incurva Roxb., and H. acerba Lindl. Random primers were designed to amplify the genome. The amplified products were detected by agarose gel electrophoresis. Results By analyzing the polymorphism of the amplified product DNA fragment, the DNA fingerprint maps of Z. jujuba Mill., Z. incurva Roxb., and H. acerba Lindl. were successfully constructed.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"763 - 771"},"PeriodicalIF":0.7,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48686857","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 The aggregation of tau hyperphosphorylation (p-tau) into neurofibrillary tangles (NFT) is a hallmark in the histopathology of Alzheimer’s disease (AD). Our previous experiments found that β-asarone could prevent injury of PC12 cells induced by A 1–42, but could it fight cell damage of p-tau induced by okadaic acid (OA) is poorly understood. Objectives The emphasis of this study lies in β-asarone’s therapeutical effect on p-tau inhibition stimulated by OA. Materials and Methods 175 nmol OA was used to establish AD cells. Cell viability rate and cell toxicity were evaluated by the CCK-8 kit and LDH kit, respectively. The p-tau, Aβ42, β-secretase, and protein phosphatase 2A (PP2A) were examined by ELISA. Proteins closely related to the pathogenesis of AD are involved p-tau, Beclin-1, p-Akt, and p-mTOR were analyzed by western-blotting and immunofluorescence detection. Results The results revealed that β-asarone enhanced cell viability induced by OA in a dose-dependent manner. Moreover, compared to the OA model, p-tau, Aβ42, β-secretase, and Beclin-1 were reduced, while PP2A, p-Akt, and p-mTOR increased after treatment with β-asarone. Conclusion All data suggested that β-asarone decreased p-tau, Aβ42, and β-secretase levels, and activated PP2A levels by inhibiting Beclin-1-dependent autophagy in OA model cells, involving Akt/mTOR/Beclin-1 pathway.
{"title":"β-asarone Protects p-tau from Okadaic Acid in PC12 Cells by Activating PP2A and Involving Akt/mTOR/Beclin-1 Pathway","authors":"Li-Ping Huang, Xiaoqin Zhong, Yuanhang Xu, Minzhen Deng, Zhongliu Zhou","doi":"10.1177/09731296231168743","DOIUrl":"https://doi.org/10.1177/09731296231168743","url":null,"abstract":"Background The aggregation of tau hyperphosphorylation (p-tau) into neurofibrillary tangles (NFT) is a hallmark in the histopathology of Alzheimer’s disease (AD). Our previous experiments found that β-asarone could prevent injury of PC12 cells induced by A 1–42, but could it fight cell damage of p-tau induced by okadaic acid (OA) is poorly understood. Objectives The emphasis of this study lies in β-asarone’s therapeutical effect on p-tau inhibition stimulated by OA. Materials and Methods 175 nmol OA was used to establish AD cells. Cell viability rate and cell toxicity were evaluated by the CCK-8 kit and LDH kit, respectively. The p-tau, Aβ42, β-secretase, and protein phosphatase 2A (PP2A) were examined by ELISA. Proteins closely related to the pathogenesis of AD are involved p-tau, Beclin-1, p-Akt, and p-mTOR were analyzed by western-blotting and immunofluorescence detection. Results The results revealed that β-asarone enhanced cell viability induced by OA in a dose-dependent manner. Moreover, compared to the OA model, p-tau, Aβ42, β-secretase, and Beclin-1 were reduced, while PP2A, p-Akt, and p-mTOR increased after treatment with β-asarone. Conclusion All data suggested that β-asarone decreased p-tau, Aβ42, and β-secretase levels, and activated PP2A levels by inhibiting Beclin-1-dependent autophagy in OA model cells, involving Akt/mTOR/Beclin-1 pathway.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"727 - 735"},"PeriodicalIF":0.7,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41970240","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}
Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the Traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat’s iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.
{"title":"Network Pharmacology and Experimental Analyses on Astragalus membranaceus (Huangqi) Effects on Endotoxin-induced Uveitis Model in Rats","authors":"Jingmin Lu, Yujie Wu, Yijing Yang, Jing-Wei Zhou, Bo Huang, ChengFeng Xie, Qinghua Peng, Xiaohua Zhang","doi":"10.1177/09731296231169576","DOIUrl":"https://doi.org/10.1177/09731296231169576","url":null,"abstract":"Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the Traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat’s iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"751 - 762"},"PeriodicalIF":0.7,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47280964","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 : 2023-06-13DOI: 10.1177/09731296231170926
Likun Sun, Jing Ren, Xiu-mei Feng, Shengli Li, Yongjing Wang, Yang Jiang, C. Zheng
Background Caffeic acid (CA) or 3,4-dihydroxycinnamic acid is a polyphenolic compound primarily found in coffee, herbs, berries, and other fruits. Its antioxidant, anti-inflammatory, and immunomodulatory effects on multiple health conditions have been evaluated and reported. CA’s anti-tumor effect has been reported in solid tumors, but evidence regarding liquid tumors such as multiple myeloma (MM) is limited. The increasing incidence of MM globally provides a justified rationale to explore the potential of CA on human MM cells through caspase-dependent induced apoptosis. Objectives The study explores CA’s therapeutic effect and mechanism on multiple myeloma. Materials and Methods We performed flow cytometry at different concentrations and time points after treating human MM cell lines (MM.1R, RPMI8226, and U266) with CA to identify apoptosis and changes in mitochondrial membrane potential. A Western blot was used to assess the expression of an apoptosis-related protein in MM cell lines. Statistical Analysis Used Student’s t-test was used to evaluate the mean difference between the experimental group and the control group. Results CA markedly induced the apoptosis of MM cells in a dose- and time-dependent manner. After co-incubation with CA, JC-1 (a cationic lipid fluorescent dye was used as an indicator of mitochondrial transmembrane potential), flow cytometry results showed that the mitochondrial membrane potential of MM cells significantly decreased, and the Western blot showed activation and cleavage of caspase-3, which is the classical marker of the mitochondrial apoptosis pathway. The experimental group was statistically significant compared with the control group (p < 0.01). Conclusion Our research demonstrated that CA induced MM cell apoptosis through disturbing mitochondrial membrane integrity, followed by caspase-3 splitting, and suggested that CA might have tremendous therapeutic potential for MM treatment.
{"title":"Caffeic Acid Markedly Induced Apoptosis of Human Multiple Myeloma Cells through the Caspase-dependent Pathway","authors":"Likun Sun, Jing Ren, Xiu-mei Feng, Shengli Li, Yongjing Wang, Yang Jiang, C. Zheng","doi":"10.1177/09731296231170926","DOIUrl":"https://doi.org/10.1177/09731296231170926","url":null,"abstract":"Background Caffeic acid (CA) or 3,4-dihydroxycinnamic acid is a polyphenolic compound primarily found in coffee, herbs, berries, and other fruits. Its antioxidant, anti-inflammatory, and immunomodulatory effects on multiple health conditions have been evaluated and reported. CA’s anti-tumor effect has been reported in solid tumors, but evidence regarding liquid tumors such as multiple myeloma (MM) is limited. The increasing incidence of MM globally provides a justified rationale to explore the potential of CA on human MM cells through caspase-dependent induced apoptosis. Objectives The study explores CA’s therapeutic effect and mechanism on multiple myeloma. Materials and Methods We performed flow cytometry at different concentrations and time points after treating human MM cell lines (MM.1R, RPMI8226, and U266) with CA to identify apoptosis and changes in mitochondrial membrane potential. A Western blot was used to assess the expression of an apoptosis-related protein in MM cell lines. Statistical Analysis Used Student’s t-test was used to evaluate the mean difference between the experimental group and the control group. Results CA markedly induced the apoptosis of MM cells in a dose- and time-dependent manner. After co-incubation with CA, JC-1 (a cationic lipid fluorescent dye was used as an indicator of mitochondrial transmembrane potential), flow cytometry results showed that the mitochondrial membrane potential of MM cells significantly decreased, and the Western blot showed activation and cleavage of caspase-3, which is the classical marker of the mitochondrial apoptosis pathway. The experimental group was statistically significant compared with the control group (p < 0.01). Conclusion Our research demonstrated that CA induced MM cell apoptosis through disturbing mitochondrial membrane integrity, followed by caspase-3 splitting, and suggested that CA might have tremendous therapeutic potential for MM treatment.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"720 - 726"},"PeriodicalIF":0.7,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41483365","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 : 2023-06-12DOI: 10.1177/09731296231171217
Dan Wang, Duochun Ji, Danni Wu, Like Wang, Chunyan Yu, C. Li, Xiaodong Gai
Background One of the key factors limiting the effectiveness of chemotherapy treatment for malignancies is multidrug resistance (MDR). The MDR phenotype is related to P-glycoprotein (P-gp) expression and function. The main triterpenoid saponins generated from Bupleurum chinense DC (BCDC), saikosaponin A (SSa), has been found to have anti-tumor potential. Saikosaponin B (SSb) has the potential for utility in combination with anticancer drugs as the secondary saikosaponins. Objective In this study, we looked into the impact of SSa and SSb on doxorubicin (Dox)-resistant breast cancer cells and its underlying mechanisms. Materials and Methods Dox-resistant breast cancer cells (MCF-7ADR) and MCF-7 cells were used in the study. The experimental cells were divided into a different concentration SSa administration group, a different concentration SSb administration group, and a control group, and the related biochemical parameters of MCF-7 and MCF-7ADR cells were detected. Results We discovered that SSa and SSb both suppressed MCF-7 and MCF-7ADR cell proliferation in a dose-dependent manner. Additionally, SSa at 2.5 and 5.0 µg/mL and SSb at 3.0 and 7.0 µg/mL could significantly enhance the cytotoxicity of Dox and reverse MDR in MCF-7ADR cells. The combination of Dox and SSa or SSb induced obvious synergistic effects. SSa and SSb could increase the sensitivity of MCF-7ADR cells to Dox by decreasing P-gp expression, increasing intracellular accumulation, and delaying the drug efflux of rhodamine 123 (Rh123, a P-gp substrate). Additionally, SSa and SSb both induced G1-phase arrest in MCF-7ADR cells in the presence of Dox. Conclusion According to the study, SSa and SSb may be novel MDR reversal medicines for breast cancer chemotherapy and have significant therapeutic significance for MDR during tumor therapy.
多药耐药(MDR)是制约恶性肿瘤化疗效果的关键因素之一。MDR表型与p -糖蛋白(P-gp)的表达和功能有关。柴胡皂苷A (saikosaponin A, SSa)是柴胡总皂苷(Bupleurum chinense DC, BCDC)的主要三萜，具有抗肿瘤作用。柴草皂苷B (SSb)作为次级柴草皂苷与抗癌药物联合使用具有潜在的应用价值。目的探讨SSa和SSb对阿霉素耐药乳腺癌细胞的影响及其机制。材料与方法采用耐药乳腺癌细胞(MCF-7ADR)和MCF-7细胞进行研究。将实验细胞分为不同浓度SSa给药组、不同浓度SSb给药组和对照组，检测MCF-7和MCF-7ADR细胞的相关生化参数。结果SSa和SSb均能抑制MCF-7和MCF-7ADR细胞的增殖，并呈剂量依赖性。此外，2.5和5.0µg/mL的SSa和3.0和7.0µg/mL的SSb可以显著增强Dox的细胞毒性并逆转MCF-7ADR细胞中的MDR。Dox与SSa或SSb联用可产生明显的协同作用。SSa和SSb可通过降低P-gp表达、增加细胞内积累、延缓罗丹明123 (P-gp底物Rh123)的药物外排来增加MCF-7ADR细胞对Dox的敏感性。此外，在Dox存在的情况下，SSa和SSb均诱导MCF-7ADR细胞的g1期阻滞。结论SSa和SSb可能是乳腺癌化疗的新型耐多药逆转药物，对肿瘤治疗期间的耐多药有重要的治疗意义。
{"title":"Reversal Effect of Saikosaponin A and Saikosaponin B on Doxorubicin-resistant Breast Cancer Cells and its Mechanism","authors":"Dan Wang, Duochun Ji, Danni Wu, Like Wang, Chunyan Yu, C. Li, Xiaodong Gai","doi":"10.1177/09731296231171217","DOIUrl":"https://doi.org/10.1177/09731296231171217","url":null,"abstract":"Background One of the key factors limiting the effectiveness of chemotherapy treatment for malignancies is multidrug resistance (MDR). The MDR phenotype is related to P-glycoprotein (P-gp) expression and function. The main triterpenoid saponins generated from Bupleurum chinense DC (BCDC), saikosaponin A (SSa), has been found to have anti-tumor potential. Saikosaponin B (SSb) has the potential for utility in combination with anticancer drugs as the secondary saikosaponins. Objective In this study, we looked into the impact of SSa and SSb on doxorubicin (Dox)-resistant breast cancer cells and its underlying mechanisms. Materials and Methods Dox-resistant breast cancer cells (MCF-7ADR) and MCF-7 cells were used in the study. The experimental cells were divided into a different concentration SSa administration group, a different concentration SSb administration group, and a control group, and the related biochemical parameters of MCF-7 and MCF-7ADR cells were detected. Results We discovered that SSa and SSb both suppressed MCF-7 and MCF-7ADR cell proliferation in a dose-dependent manner. Additionally, SSa at 2.5 and 5.0 µg/mL and SSb at 3.0 and 7.0 µg/mL could significantly enhance the cytotoxicity of Dox and reverse MDR in MCF-7ADR cells. The combination of Dox and SSa or SSb induced obvious synergistic effects. SSa and SSb could increase the sensitivity of MCF-7ADR cells to Dox by decreasing P-gp expression, increasing intracellular accumulation, and delaying the drug efflux of rhodamine 123 (Rh123, a P-gp substrate). Additionally, SSa and SSb both induced G1-phase arrest in MCF-7ADR cells in the presence of Dox. Conclusion According to the study, SSa and SSb may be novel MDR reversal medicines for breast cancer chemotherapy and have significant therapeutic significance for MDR during tumor therapy.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"700 - 708"},"PeriodicalIF":0.7,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42635848","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 : 2023-06-12DOI: 10.1177/09731296231169577
Yeting Zhu, Jiangsong Peng, Yaqin Zhao, Mengru Wu, Suping Chen, Jiali Shao, Xubo Wang, G. Xia, Yuping Shen
Background Prosaikogenin F (PSF) has stronger anti-cancer bioactivity than saikosaponin A (SSA), however, it was hardly isolated due to its trace amount in the raw material of Radix Bupleuri (RB). In addition, the active chemical constituent was unstable under acidic conditions owing to a 13,28-epoxy-ether moiety at the D ring of its aglycone. Objectives This study was to develop an appropriate method for obtaining acid-sensitive PSF from SSA abundant in RB. Materials and Methods Enzymatic hydrolysis was employed and snailase was selected due to its good hydrolysis performance under nearly neutral circumstances. Hydrolysis conditions were then optimized by one-factor-at-a-time experimentation before response surface methodology (RSM) by Box-Behnken Design (BBD). Results The reaction system was constructed in Na2HPO4-NaH2PO4 buffer (pH 6.0) containing snailase/SSA (44:1) at 39°C, then the hydrolysis lasted for 12 h. Therefore, the highest conversion ratio of SSA was achieved at 100.0%. Conclusion The newly proposed method is eco-friendly for obtaining acid-sensitive PSF, which lays a solid foundation for its development to be an anti-cancer new drug.
背景Prosaikogenin F (PSF)具有比saikosaponin A (SSA)更强的抗癌活性，但由于其在柴胡(RB)的原料中含量极低，很难被分离出来。此外，由于其糖苷元D环上的13,28-环氧醚部分，其活性化学成分在酸性条件下不稳定。目的研究从RB中丰富的SSA提取酸敏感PSF的合适方法。材料与方法采用酶解法，选择蜗牛酶，因为蜗牛酶在接近中性的条件下具有良好的水解性能。然后采用Box-Behnken Design (BBD)响应面法(RSM)前单因素试验优化水解条件。结果在含snailase/SSA(44:1)的Na2HPO4-NaH2PO4缓冲液(pH 6.0)中，在39℃条件下建立反应体系，水解12 h, SSA的最高转化率为100.0%。结论该方法是一种环境友好的酸敏PSF制备方法，为其成为抗癌新药奠定了坚实的基础。
{"title":"Obtaining Acid-sensitive Prosaikogenin F by Enzymatic Hydrolysis of Saikosaponin A","authors":"Yeting Zhu, Jiangsong Peng, Yaqin Zhao, Mengru Wu, Suping Chen, Jiali Shao, Xubo Wang, G. Xia, Yuping Shen","doi":"10.1177/09731296231169577","DOIUrl":"https://doi.org/10.1177/09731296231169577","url":null,"abstract":"Background Prosaikogenin F (PSF) has stronger anti-cancer bioactivity than saikosaponin A (SSA), however, it was hardly isolated due to its trace amount in the raw material of Radix Bupleuri (RB). In addition, the active chemical constituent was unstable under acidic conditions owing to a 13,28-epoxy-ether moiety at the D ring of its aglycone. Objectives This study was to develop an appropriate method for obtaining acid-sensitive PSF from SSA abundant in RB. Materials and Methods Enzymatic hydrolysis was employed and snailase was selected due to its good hydrolysis performance under nearly neutral circumstances. Hydrolysis conditions were then optimized by one-factor-at-a-time experimentation before response surface methodology (RSM) by Box-Behnken Design (BBD). Results The reaction system was constructed in Na2HPO4-NaH2PO4 buffer (pH 6.0) containing snailase/SSA (44:1) at 39°C, then the hydrolysis lasted for 12 h. Therefore, the highest conversion ratio of SSA was achieved at 100.0%. Conclusion The newly proposed method is eco-friendly for obtaining acid-sensitive PSF, which lays a solid foundation for its development to be an anti-cancer new drug.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"689 - 699"},"PeriodicalIF":0.7,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43642195","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 : 2023-06-09DOI: 10.1177/09731296231170931
Anisha Lyngdoh, T. Baruah, R. Sharan, Lakhon Kma
Background Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with a recurrence rate of 80–90% and a high mortality rate. It is an inflammation-related cancer where cytokines production plays a major role, resulting in a non-resolving inflammation in the tumor microenvironment, which promotes the disease. Therefore, targeting inflammation is a logical way to combat HCC. Natural products can be helpful in the co-treatment and prevention of HCC. Hypothesis This study aimed to evaluate the hepatoprotective properties of a methanolic extract of Apium graveolens L. (MAG) in diethylnitrosamine (DEN)-induced toxicity in BALB/c mice. Materials and Methods We checked the antioxidant, anti-inflammatory, and anti-cancer properties of MAG. DEN is known to induce oxidative stress by increasing reactive oxygen species (ROS) production. This can result in liver damage, increased SGOT, SGPT, and ALP activity in serum, increased expression of HCC biomarkers like AFP and GPC-3, and increased levels of the inflammatory biomarkers NF-κB, IL-6, IL-4, IL-1β, and TNF-α. The above factors can cause the activation of the inflammatory signaling pathways, triggering the development of HCC. Results MAG was able to lower the detrimental effects of DEN by restoring liver function; decrease oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), and ϒ-L-glutamyl-L-Cysteinyl-glycine (GSH); decrease the inflammatory factors responsible for HCC; and increase caspase-3 activity. Molecular docking studies showed how phytoconstituents like luteolin, apigenin, and kaempferol present in MAG could potentially be responsible for lowering the effects of DEN in the mice’s liver. Conclusion Altogether, the present study showed that MAG was able to ameliorate inflammation in the DEN-induced liver carcinogenesis in BALB/c mice. To the best of the authors’ knowledge, this is the first report on the use of a whole plant (Apium graveolens) in an anti-cancer study in a mouse model.
{"title":"Inhibitory Potential of Apium graveolens L. Extract on Inflammation in Diethylnitrosamine-induced Hepatocellular Carcinoma in Mice","authors":"Anisha Lyngdoh, T. Baruah, R. Sharan, Lakhon Kma","doi":"10.1177/09731296231170931","DOIUrl":"https://doi.org/10.1177/09731296231170931","url":null,"abstract":"Background Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with a recurrence rate of 80–90% and a high mortality rate. It is an inflammation-related cancer where cytokines production plays a major role, resulting in a non-resolving inflammation in the tumor microenvironment, which promotes the disease. Therefore, targeting inflammation is a logical way to combat HCC. Natural products can be helpful in the co-treatment and prevention of HCC. Hypothesis This study aimed to evaluate the hepatoprotective properties of a methanolic extract of Apium graveolens L. (MAG) in diethylnitrosamine (DEN)-induced toxicity in BALB/c mice. Materials and Methods We checked the antioxidant, anti-inflammatory, and anti-cancer properties of MAG. DEN is known to induce oxidative stress by increasing reactive oxygen species (ROS) production. This can result in liver damage, increased SGOT, SGPT, and ALP activity in serum, increased expression of HCC biomarkers like AFP and GPC-3, and increased levels of the inflammatory biomarkers NF-κB, IL-6, IL-4, IL-1β, and TNF-α. The above factors can cause the activation of the inflammatory signaling pathways, triggering the development of HCC. Results MAG was able to lower the detrimental effects of DEN by restoring liver function; decrease oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), and ϒ-L-glutamyl-L-Cysteinyl-glycine (GSH); decrease the inflammatory factors responsible for HCC; and increase caspase-3 activity. Molecular docking studies showed how phytoconstituents like luteolin, apigenin, and kaempferol present in MAG could potentially be responsible for lowering the effects of DEN in the mice’s liver. Conclusion Altogether, the present study showed that MAG was able to ameliorate inflammation in the DEN-induced liver carcinogenesis in BALB/c mice. To the best of the authors’ knowledge, this is the first report on the use of a whole plant (Apium graveolens) in an anti-cancer study in a mouse model.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"736 - 750"},"PeriodicalIF":0.7,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48285699","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 Membranous nephropathy (MN), one of the primary pathogenic forms of adult nephrotic syndromes, frequently coexists with hypercoagulability and hyperviscosity. MN is prone to thrombosis, embolism, and other complications, leading to the accelerated occurrence of glomerulosclerosis and renal fibrosis. Therefore, it is particularly important to promote blood circulation and remove stasis through anticoagulant therapy. Salvianolate (SAL) is a Chinese patent anticoagulant commonly used in clinical practice to promote blood circulation and remove blood stasis. SAL plays an important role in alleviating urinary protein and renal pathological damage in MN patients. Objectives In the present study, we aimed to investigate the kidney-protective effect of SAL on MN in a rat model. Materials and Methods The rat model of MN was established by tail vein injection of cationic bovine serum albumin (C-BSA). After the treatment, urinary proteins, hypercoagulable state index (fibrinogen (Fib), D dimer (D-D)), hepatic and renal functions, renal pathology, and podocyte marker proteins were analyzed to explore the renal protective effect of SAL on MN rats and its underlying mechanism. Results In the modeled rats, we discovered a significant rise in urinary protein, a hypercoagulable state, and hypoproteinemia. Additionally, the expressions of Wilms’ tumor protein 1 (WT-1), podocalyxin (PCX), and vascular endothelial growth factor (VEGF) in renal tissues were significantly downregulated, indicating remarkable pathological damage to podocytes and renal tissues in MN rats. The expressions of the above-mentioned indices could be greatly reversed by SAL, which could also regulate the hypercoagulable state and suppress podocyte damage and renal pathological harm. Conclusion Our results suggested that the renal protective effect of SAL on C-BSA-induced MN was related to its ability to inhibit hypercoagulable states, upregulate the expressions of WT-1, PCX, and VEGF in the renal tissue, and repair podocyte injury.
{"title":"Salvianolate Ameliorates Renal Damage Induced by C-BSA in Membranous Nephropathy Rats Through Inhibiting Hypercoagulable State and Alleviating Podocyte Injury","authors":"Wenjun Chen, Jin-Man Tan, Suzhi Chen, Fengwen Yang, Huiming Yan, Huiling Duo, Huijie Zhou","doi":"10.1177/09731296231170082","DOIUrl":"https://doi.org/10.1177/09731296231170082","url":null,"abstract":"Background Membranous nephropathy (MN), one of the primary pathogenic forms of adult nephrotic syndromes, frequently coexists with hypercoagulability and hyperviscosity. MN is prone to thrombosis, embolism, and other complications, leading to the accelerated occurrence of glomerulosclerosis and renal fibrosis. Therefore, it is particularly important to promote blood circulation and remove stasis through anticoagulant therapy. Salvianolate (SAL) is a Chinese patent anticoagulant commonly used in clinical practice to promote blood circulation and remove blood stasis. SAL plays an important role in alleviating urinary protein and renal pathological damage in MN patients. Objectives In the present study, we aimed to investigate the kidney-protective effect of SAL on MN in a rat model. Materials and Methods The rat model of MN was established by tail vein injection of cationic bovine serum albumin (C-BSA). After the treatment, urinary proteins, hypercoagulable state index (fibrinogen (Fib), D dimer (D-D)), hepatic and renal functions, renal pathology, and podocyte marker proteins were analyzed to explore the renal protective effect of SAL on MN rats and its underlying mechanism. Results In the modeled rats, we discovered a significant rise in urinary protein, a hypercoagulable state, and hypoproteinemia. Additionally, the expressions of Wilms’ tumor protein 1 (WT-1), podocalyxin (PCX), and vascular endothelial growth factor (VEGF) in renal tissues were significantly downregulated, indicating remarkable pathological damage to podocytes and renal tissues in MN rats. The expressions of the above-mentioned indices could be greatly reversed by SAL, which could also regulate the hypercoagulable state and suppress podocyte damage and renal pathological harm. Conclusion Our results suggested that the renal protective effect of SAL on C-BSA-induced MN was related to its ability to inhibit hypercoagulable states, upregulate the expressions of WT-1, PCX, and VEGF in the renal tissue, and repair podocyte injury.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"19 1","pages":"678 - 688"},"PeriodicalIF":0.7,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44749562","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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