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Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-KB Pathway in H9c2 Cardiomyocytes 被引量:21
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作者 Yan-yan MENG Yuan LIU +6 位作者 Zhe-fu HU Yao ZHANG Jian NI Zhen-guo MA Hai-han LIAO Qing-qing WU Qi-zhu TANG 《Current Medical Science》 SCIE CAS 2018年第2期204-211,共8页
The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, a... The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaceharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear faetor-κB (NF-κB) signaling pathways. As a result, increased mRNA expression of interleukin (IL)-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis ofHge2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction. 展开更多
关键词 LIPOPOLYSACCHARIDES sanguinarinE INFLAMMATION H9c2 cardiac cells APOPTOSIS
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Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives 被引量:12
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作者 Roberta Gaziano Gabriella Moroni +3 位作者 Cristina Buè Martino Tony Miele Paola Sinibaldi-Vallebona Francesca Pica 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2016年第1期30-39,共10页
Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtaine... Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice. 展开更多
关键词 sanguinarinE Cancer Apoptosis CELL-CYCLE CHEMOTHERAPY
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Spectral studies of the interaction between sanguinarine and guanosine 被引量:1
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作者 Zuo Peng Du Quan Ling Suo +2 位作者 Xiao Yan Zhang Ling Wei Zhang Xiong Hui Wei 《Chinese Chemical Letters》 SCIE CAS CSCD 2008年第12期1465-1469,共5页
The interaction between sanguinarine and guanosine was investigated by using UV-vis and fluorescence spectra at pH 7.2. The binding of sanguinarine to guanosine was substantiated by the hypochromism and bathochromism ... The interaction between sanguinarine and guanosine was investigated by using UV-vis and fluorescence spectra at pH 7.2. The binding of sanguinarine to guanosine was substantiated by the hypochromism and bathochromism in the absorption spectra and the emission quenching in fluorescence spectra. The fluorescence lifetime results, the varieties of the fluorophore absorption spectra and the decrease of the binding constant with the increasing temperature all indicate that the fluorescence quenching is static. The ratio and constant of the binding cytidine to sanguinarine are 2 and 6.44 × 10^7, respectively. The result shows that the binding of sanguinarine to guanosine is not only exothermic but also entropy-driven with △H=-8.53kJ/mol, AS = 0.12 kJ/(molK), and AG =-44.57 kJ/mol at 298.15 K. 展开更多
关键词 sanguinarinE GUANOSINE SPECTROSCOPY INTERACTION
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Stability of Sanguinarine and Chelerythrine in Macleaya cordata (Willd.) R. Br. 被引量:1
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作者 Chunmei LI Xu CHEN +3 位作者 Wenlan LI Bingmei LIU Li WANG Yubin JI 《Medicinal Plant》 CAS 2019年第6期20-23,共4页
[Objectives]To explore the stability of sanguinarine and chelerythrine in Macleaya cordata(Willd.)R.Br.[Methods]The solubility and stability of sanguinarine and chelerythrine in seven solvents were measured by HPLC.Be... [Objectives]To explore the stability of sanguinarine and chelerythrine in Macleaya cordata(Willd.)R.Br.[Methods]The solubility and stability of sanguinarine and chelerythrine in seven solvents were measured by HPLC.Besides,the effects of water quality,light source,oxidant,temperature,and pH on stability were investigated.[Results]The solubility and stability of sanguinarine and chelerythrine in methanol and ethanol are good;the stability of sanguinarine and chelerythrine in distilled water and rainwater is not affected by light and is very stable,but they are unstable in tap water whether they are protected from light or not;oxidants have a great influence on the stability of sanguinarine and chelerythrine;sanguinarine and chelerythrine are stable at room temperature lower than 54℃;sanguinarine is stable in pH 2.5-7.0,while chelerythrine is stable in pH 2.5-8.0.[Conclusions]The good stability of sanguinarine and chelerythrine under specific conditions shows that they have broad development prospects and value. 展开更多
关键词 Macleaya cordata(Willd.)R.Br. sanguinarinE CHELERYTHRINE STABILITY
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Sanguinarine-Mediated Sensitization of Cervical Cancer SiHa Cells to TRAIL
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作者 Eric Romney Whitney Wilson +5 位作者 Justin Chen Trung Nguyen Omar Jawhar Aniket Mody Shaleen Korch Vinay J Nagaraj 《Journal of Cancer Therapy》 2017年第6期624-635,共12页
Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of a... Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of apoptosis in transformed cells is a key strategy in successfully treating HPV-induced cervical cancer. TRAIL (tumor necrosis factor related apoptosis-inducing ligand) has been shown to selectively induce apoptosis in cancer cells by binding to death receptors and activating extrinsic pathways for apoptosis. However, certain cervical cancers—such as the cultured cell line SiHa—are remarkably resistant to TRAIL. In this study, SiHa cells were sensitized to TRAIL by using sanguinarine—derived from the plant Sanguinaria Canadensis—which is known to induce oxidative stress and lead to the upregulation of receptors for TRAIL. Methods: Cultured SiHa cells were exposed to sub-lethal doses of sanguinarine in combination with TRAIL. Cell viability changes as well as the production of reactive oxygen species (ROS) were assessed. The induction of apoptosis was investigated by assays for caspase activation. Flow cytometry was performed to analyze expression of death receptors 4/5. Results: Treatment of SiHa cells with a combination of sanguinarine and TRAIL led to a significant reduction in cell viability. Significant increase in ROS was observed and caspase activation assays confirmed the induction of apoptosis. Conclusions: The observed synergistic effect of sanguinarine and TRAIL on SiHa cells is promising for the treatment of cervical, and possibly other, HPV-induced cancers. Oxidative stress caused by sanguinarine seems to play a central role in this synergy. The precise link between reactive oxygen species and the possible upregulation of death receptors needs further investigation. This knowledge will enable us to devise more effective treatments for those who suffer from this devastating disease. 展开更多
关键词 Cervical Cancer SIHA Cells Human PAPILLOMA Virus (HPV) sanguinarinE TRAIL (Tumor NECROSIS Factor Related Apoptosis-Inducing Ligand)
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Simultaneous Quantitative Determination of Nitidine, Chelerythrine and Sanguinarine Using HPTLC from Callus Extract of <i>Zanthoxylum rhetsa</i>
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作者 Kavitha Perala Veeresham Ciddi 《American Journal of Analytical Chemistry》 2018年第8期386-396,共11页
Nitidine, Chelerythrine and Sanguinarine, all these three alkaloids are benzophenanthridine alkaloids. Nitidine was used as an anti-HIV, anti-malarial and anti-cancer. Chelerythrine had anti-cancer and anti-inflammato... Nitidine, Chelerythrine and Sanguinarine, all these three alkaloids are benzophenanthridine alkaloids. Nitidine was used as an anti-HIV, anti-malarial and anti-cancer. Chelerythrine had anti-cancer and anti-inflammatory activities. Sanguinarine was widely used as an anti-plaquestic and anti-cancer. High performance thin layer chromatography (HPTLC) method was used for simultaneous quantification of Nitidine, Chelerythrine and Sanguinarine in callus extract of Zanthoxylum rhetsa by using Silica gel 60 F254 as stationary phase and ethyl acetate:methanol:water:diethylamine (30:5:2:0.5 v/v) as mobile phase at 280 nm. The linearity concentration range was 5 - 160 μg/band of each alkaloid. The Rf values of Nitidine, Chelerythrine and Sanguinarine were found to be 0.28, 0.49 and 0.73. The limit of detection and limit of quantification were found to be 0.026, 0.088 μg/spot and 0.010 and 0.033 μg/spot, 0.0104 and 0.035 μg/spot respectively for Nitidine, Chelerythrine and Sanguinarine. HPTLC method was developed and validated according to ICH guidelines for simultaneous estimation of Nitidine, Chelerythrine and Sanguinarine and proved to be simple, specific, accurate, robust and rapid. 展开更多
关键词 Nitidine CHELERYTHRINE sanguinarinE HPTLC
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Systematic understanding of the underlying target and mechanism of sanguinarine against nasopharyngeal carcinoma through a networkpharmacology approach
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作者 Meng-Zhe Yang Bei-Bei Zhang +8 位作者 Zhen-Qiang Liang Ning Xu Nan-Nan Cheng An-Qiao Lv Jian-Yu Yang Xing-Zhe Guo Xian-Yu Bai Ai-Jun Jiao Yuan-Jiao Huang 《Precision Medicine Research》 2020年第3期104-115,共12页
Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in r... Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in recent years,which has been effectively used to predict the potential therapeutic compounds against disease focusing on the possible therapeutic targets and mechanisms.Sanguinarine,a traditional natural plant-derived phenanthridine alkaloid,has been reported to have a wide variety of pharmacological activities for decades.Methods:In the current study,using the comprehensive network pharmacological method,the potential drug targets of sanguinarine against nasopharyngeal carcinoma were successfully predicted,and verified by molecular docking.The underlying pharmacological mechanism was initially unraveled.Results:Totally,38 potential common targets were confirmed from these potential nasopharyngeal carcinoma therapeutic targets and pharmacological targets of sanguinarine.Their enrichment analyses of GO functions show that protein serine/threonine kinase activity,histone kinase activity,integrin binding,protein tyrosine kinase activity,and cell adhesion molecule binding were top listed.KEGG functional enrichment analysis indicates that the potential pathways are mainly involved into PI3K-Akt signaling pathway.The"drug-target-disease-pathway"network model diagram points out the key genes containing MAPK10,MAPK14,JAK2,BRAF,GSK3B,MET,HSP90AA1,SRC,et al..According to the results of molecular docking,it was further verified that sanguinarine has strong binding ability with MAPK10 and MAPK14.Conclusion:Taken together,this study would provide a clarified theoretical basis for the subsequent wet laboratory research focusing on sanguinarine against nasopharyngeal carcinoma. 展开更多
关键词 Nasopharyngeal carcinoma sanguinarinE Network pharmacology Drug target
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Binding of nucleosides with the cytotoxic plant alkaloid sanguinarine:Spectroscopic and thermodynamic studies
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作者 ZHANG JianBin DU ZuoPeng WEI XiongHui 《Science China Chemistry》 SCIE EI CAS 2012年第9期1895-1902,共8页
In spite of a large number of studies of the interaction of the cytotoxic plant alkaloid sanguinarine(SAN) with nucleic acids,the anticancer mechanism of SAN is still not clear.In contrast to the large number of studi... In spite of a large number of studies of the interaction of the cytotoxic plant alkaloid sanguinarine(SAN) with nucleic acids,the anticancer mechanism of SAN is still not clear.In contrast to the large number of studies of the interaction mechanism of SAN with DNA,there have been relatively few studies of the interaction of SAN with nucleosides.In this work,the interaction of SAN with three nucleosides-thymidine(T),uridine(U),and adenosine(A)-was investigated using a combination of conventional fluorescence and UV-vis spectroscopic techniques;thermodynamic calculations were also carried out at physiological pH 7.2.The binding processes of SAN with the different nucleosides were characterized by hypochromic and bathochromic effects in the absorption spectra of SAN and by the quenching of the fluorescence intensity of SAN.The measurements of fluorescence lifetime,the variations of the absorption spectra of the fluorophore,and the dependence of the quenching on the temperature indicated that the fluorescence quenching is static.The Stern-Volmer plot is nonlinear and approximately quadratic showing that,in this process,one SAN molecule can bind with two nucleoside molecules.These studies,together with our earlier studies of the binding of SAN with cytidine(C) and guanosine(G),showed that the binding constants of SAN with the five nucleosides at T = 308.15,318.15,and 328.15 K decreased in the order C > G > T > U > A and at T = 298.15 K decreased in the order G > C > T > U > A,and that the binding of SAN with the various nucleosides is not only slightly exothermic but also entropy-driven.All these results together with fluorescence quenching experiments advance good evidence concerning the interaction of SAN with various nucleosides.Such studies of the interaction mechanism of alkaloids with DNA may promote the development of new drugs. 展开更多
关键词 sanguinarinE NUCLEOSIDES BINDING spectroscopy thermodynamics
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Sanguinarine suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma via inhibiting mTOR signaling
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作者 YANG Mengzhe ZHANG Beibei +8 位作者 LIANG Zhenqiang CHENG Nannan LüAnqiao YANG Jianyu GUO Xingzhe BAI Xianyu HUANG Yuanjiao JIAO Aijun XU Ning 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2022年第5期687-692,共6页
OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch t... OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch test, transwell migration and invasion experiment and flow cytometry-based cell apoptosis assay were further performed. In addition, Western blotting was performed to investigate the cell signaling pathway. All the relevant experimental data were statistically processed using SPSS 16.0 software.RESULTS: The results showed that sanguinarine represented a time and dose dependent inhibition effects on NPC cell proliferation including the low differentiated CNE2 cells and high metastatic 5-8F cells, along with the cell cloning ability reduction. In addition, sanguinarine has a certain inhibitory effect on the invasion and migration of NPC cells. Mechanistically, sanguinarine displayed the anti-NPC effects mainly involved into the suppression of m TOR signaling and cell apoptosis, which is closely associated with the tumor growth and metastatic malignancy. CONCLUSIONS: Collectively, we discover that sanguinarine is a new high-efficiency anti-NPC monomer of Chinese medicine, with a value for the follow-up preclinical research. 展开更多
关键词 nasopharyngeal carcinoma sanguinarinE TOR serine-threonine kinases apoptosis
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液相色谱-串联质谱法测定饲料中的血根碱和白屈菜红碱
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作者 郑国建 叶寅颖 +1 位作者 雷涛 曹莹 《饲料工业》 CAS 北大核心 2024年第7期139-144,共6页
研究旨在建立液相色谱-串联质谱法(LC-MS/MS)检测饲料中血根碱和白屈菜红碱含量的分析方法。饲料样品用15 mL、0.2%盐酸乙腈溶液超声提取2次,每次20 min,提取液使用HLB固相萃取柱净化、微孔滤膜过滤后进行液相色谱-串联质谱法测定,用外... 研究旨在建立液相色谱-串联质谱法(LC-MS/MS)检测饲料中血根碱和白屈菜红碱含量的分析方法。饲料样品用15 mL、0.2%盐酸乙腈溶液超声提取2次,每次20 min,提取液使用HLB固相萃取柱净化、微孔滤膜过滤后进行液相色谱-串联质谱法测定,用外标法定量,对检测方法进行验证。结果显示:在质量浓度为1~100 ng/mL范围内其线性相关系数≥0.999,定量限为0.005 mg/kg,回收率为91.9%~101.0%,相对标准偏差为2.00%~7.96%。表明所建立的液相色谱-串联质谱法结果准确、重复性好,适用于饲料中血根碱和白屈菜红碱的测定。 展开更多
关键词 血根碱 白屈菜红碱 液相色谱-串联质谱法 饲料 添加剂
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血根碱对腰椎间盘突出症大鼠炎性疼痛的改善作用及机制 被引量:1
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作者 阮祯 何生华 +2 位作者 龚雪花 乔松 王超 《中国药房》 CAS 北大核心 2024年第9期1087-1093,共7页
目的研究血根碱(SG)对腰椎间盘突出症(LDH)大鼠炎性疼痛的改善作用及机制。方法制备LDH模型大鼠,然后分为模型组和SG低、中、高剂量组(1.00、2.50、6.25 mg/kg)以及SG高剂量+Anisomycin[丝裂原活化蛋白激酶(MAPK)激活剂]组(6.25 mg/kg S... 目的研究血根碱(SG)对腰椎间盘突出症(LDH)大鼠炎性疼痛的改善作用及机制。方法制备LDH模型大鼠,然后分为模型组和SG低、中、高剂量组(1.00、2.50、6.25 mg/kg)以及SG高剂量+Anisomycin[丝裂原活化蛋白激酶(MAPK)激活剂]组(6.25 mg/kg SG+5 mg/kg Anisomycin),每组10只;另取10只大鼠作为对照组。各组大鼠腹腔注射相应药物,对照组和模型组大鼠腹腔注射等体积生理盐水,每天1次,连续7 d。观察大鼠一般情况及神经功能变化;测定大鼠疼痛阈值[包括机械刺激缩足反射阈值(PWMT)和热刺激缩足反射潜伏期(PWTL)];观察大鼠背根神经节(DRG)组织病理变化;检测大鼠血清中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)]和疼痛因子[神经肽Y(NPY)、5羟色胺(5-HT)]水平;观察脊髓小胶质细胞中离子钙接头蛋白1(Iba-1)和星形胶质细胞中胶质原纤维酸性蛋白(GFAP)的阳性表达;检测大鼠DRG组织中MAPK/胞外信号调节激酶(ERK)/核因子κB(NF-κB)信号通路相关蛋白和TNF-α、IL-1β蛋白的表达。结果与对照组相比,模型组大鼠精神食欲不振,后肢运动障碍,DRG椎间盘神经元细胞排列紊乱;神经功能评分,血清中TNF-α、IL-1β、NPY水平,Iba-1、GFAP阳性表达,DRG组织中p38 MAPK、ERK1/2、NF-κB p65蛋白磷酸化水平和TNF-α、IL-1β蛋白表达水平均显著升高(P<0.05);PWMT、PWTL和血清中5-HT水平均显著降低(P<0.05)。与模型组相比,SG各剂量组大鼠精神食欲好转,后肢运动障碍缓解,DRG椎间盘神经元结构改善,上述定量指标水平均显著逆转(P<0.05)。Anisomycin可逆转SG对LDH大鼠炎性疼痛的改善作用。结论SG可通过抑制LDH大鼠DRG组织中小胶质细胞活化,减少炎症因子释放,提高疼痛阈值,从而改善炎性疼痛;其作用机制可能与抑制MAPK/ERK/NF-κB信号通路有关。 展开更多
关键词 血根碱 腰椎间盘突出症 炎性疼痛 MAPK/ERK/NF-κB信号通路
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血根碱对膀胱癌T24细胞增殖迁移的调控作用及其机制
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作者 潘登 许浩 +5 位作者 马雨阳 王靖凯 王海跞 徐鹏 庞昆 陈波 《山东医药》 CAS 2024年第20期1-5,共5页
目的 观察血根碱对膀胱癌T24细胞增殖迁移的调控作用,并探索可能的作用靶基因及作用机制。方法 培养膀胱癌T24细胞和人正常膀胱上皮细胞SV-HUC-1,分别分为实验组和对照组,实验组分别加入0.012 5、0.025、0.05、0.1、0.2、0.4、0.8、1.6... 目的 观察血根碱对膀胱癌T24细胞增殖迁移的调控作用,并探索可能的作用靶基因及作用机制。方法 培养膀胱癌T24细胞和人正常膀胱上皮细胞SV-HUC-1,分别分为实验组和对照组,实验组分别加入0.012 5、0.025、0.05、0.1、0.2、0.4、0.8、1.6μmol/L的血根碱,对照组培养基中不加血根碱,采用CCK-8试剂盒检测细胞增殖能力,并计算半数抑制浓度(IC_(50))。将T24细胞分为实验组和对照组,实验组给予血根碱,对照组不进行血根碱处理,采用Transwell小室实验检测细胞迁移能力。分别基于BATMAN、SwissTargetPrediction网络药理学数据库、TCGA数据库分析并筛选得到血根碱作用靶基因和膀胱癌治疗靶基因的交集靶基因,进行GO分析和KEGG功能富集分析,绘制蛋白质相互作用网络,筛选血根碱调控T24细胞的靶基因。采用GSEA_4.2.3进行靶基因集富集分析,以确定靶基因富集的相关通路。基于GEPIA网站和“survival”R软件包评估靶基因高表达组和低表达组的无进展间隔期、疾病特异性生存期、总生存期差异。将血根碱和靶基因蛋白结构进行分子对接,并计算结合能。采用实时荧光定量PCR法检测实验组和对照组细胞中的靶基因。结果 实验组T24细胞增殖能力和穿膜细胞数低于对照组(P均<0.05)。血根碱对T24细胞的IC_(50)为0.200 3μmol/L、对SV-HUC-1细胞的IC_(50)为0.709 9μmol/L。筛选出血根碱调控T24细胞的靶基因为基质金属蛋白酶(MMP)-2、MMP-9、前列腺素—内过氧化物合酶2(PTGS2)。MMP-2、MMP-9、PTGS2与调节上皮细胞增殖的通路有关。MMP-9高表达者疾病特异性生存期和总生存期低于低表达者(P均<0.05)。血根碱与MMP-2、MMP-9、PTGS2结合能分别为-8.8、-8.6、-10.0 kcal/mol。实验组PTGS2、MMP-2、MMP-9 mRNA表达低于对照组(P均<0.05)。结论 血根碱可在不影响SV-HUC-1细胞的浓度下抑制膀胱癌T24细胞的增殖迁移能力。血根碱对膀胱癌细胞增殖迁移能力的调控作用可能与调控MMP-2、MMP-9、PTGS2表达并影响上皮细胞增殖相关通路有关。 展开更多
关键词 血根碱 膀胱癌 细胞增殖 细胞迁移 基质金属蛋白酶2 基质金属蛋白酶9 前列腺素—内过氧化物合酶2
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血根碱壳聚糖微球的制备工艺优化及体内外性能研究 被引量:1
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作者 李春梅 史彤辉 +2 位作者 陈旭 张馨元 周长胜 《特产研究》 2024年第2期36-46,共11页
本研究旨在探讨血根碱壳聚糖微球的最优制备方法,并对微球进行外观粒径表征和体内外研究。本研究建立了血根碱含量测定的HPLC法,运用乳化交联法制备血根碱壳聚糖微球,以载药量、包封率和平均粒径为评价指标,应用单因素试验和星点设计-... 本研究旨在探讨血根碱壳聚糖微球的最优制备方法,并对微球进行外观粒径表征和体内外研究。本研究建立了血根碱含量测定的HPLC法,运用乳化交联法制备血根碱壳聚糖微球,以载药量、包封率和平均粒径为评价指标,应用单因素试验和星点设计-响应面法优化制备处方。利用显微镜和扫描电镜观察微球外观形态,通过激光粒度仪测定微球粒径及其分布。采用动态透析法取不同时间点的血根碱原料药溶液和血根碱壳聚糖微球溶液,并考察两种溶液的体外释放度,最后进行药动学方程拟合。对不同组小鼠注射血根碱原料液和血根碱微球液,不同时间取组织血测定,观察体内分布及靶向性。结果表明:血根碱HPLC含量测定得曲线方程y=2.530 0x+43.323 1(R^(2)=0.999 8,线性范围为10.0~50.0μg/mL)。单因素试验和星点设计-响应面法得最优处方:血根碱投药量60 mg,壳聚糖用量70mg,乳化剂用量5%,戊二醇用量0.25mL、水油体积比3:10,醋酸浓度2%、搅拌速度500r/min和交联时间3.5h。观察到血根碱壳聚糖微球形态近似球形及表面较光滑,测定得平均粒径(8.17±0.16)μm,粒径分布为2~20μm。体外释放显示,血根碱壳聚糖微球较血根碱原料药释放缓慢,Ritger-Peppas方程拟合效果较好(R^(2)=0.980 8)。血根碱微球在小鼠体内有明显缓释作用,在肺部和肝脏存在不同程度靶向性。血根碱壳聚糖微球体外释放具有明显的缓释作用,在小鼠体内分布具有一定靶向性和缓释性。 展开更多
关键词 血根碱 微球 星点设计-响应面法 体外释放 缓释 靶向性
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血根碱通过调控STUB1/GPX4诱导直肠癌细胞发生铁死亡
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作者 张银亮 骆泽谭 +6 位作者 赵睿 赵娜 徐志东 奥迪 丛古一 刘新宇 郑海伦 《南方医科大学学报》 CAS CSCD 北大核心 2024年第8期1537-1544,共8页
目的探究血根碱(SAN)对结直肠癌细胞增殖及铁死亡的影响。方法SW620和HCT-116细胞体外培养,在SW620细胞加入浓度分别为0、0.5、1、1.5、2、2.5、3μmol/L的SAN,HCT-116细胞加入0、0.5、0.75、1、1.25、1.5、1.75、2μmol/L的SAN。采用C... 目的探究血根碱(SAN)对结直肠癌细胞增殖及铁死亡的影响。方法SW620和HCT-116细胞体外培养,在SW620细胞加入浓度分别为0、0.5、1、1.5、2、2.5、3μmol/L的SAN,HCT-116细胞加入0、0.5、0.75、1、1.25、1.5、1.75、2μmol/L的SAN。采用CCK8法检测检测细胞活力,并计算出IC50;检测SAN对细胞的增殖抑制作用采用集落克隆实验;Transwell实验观测SAN对细胞侵袭迁移力的影响;ROS检测试剂盒通过流式细胞仪分析细胞ROS含量的变化;丙二醛(MDA)检测盒来检测脂质过氧化物的产生。氧化型谷胱甘肽/还原型谷胱甘肽定量试剂盒测定谷胱甘肽(GSH)水平。Western blotting法检测铁死亡相关蛋白(STUB1、GPX4)的表达。结果CCK8、集落克隆的结果显示,SAN可显著抑制SW620和HCT-116细胞增殖(P<0.05);Transwell实验结果显示,SAN可抑制SW620和HCT-116细胞侵袭迁移能力(P<0.05);流式细胞术检测显示:SAN显著促进SW620和HCT-116细胞内ROS的产生(P<0.05);MDA检测结果显示,SAN可使SW620和HCT-116细胞内MDA含量增加(P<0.05);GSH检测结果显示,SAN使SW620和HCT-116细胞内GSH下降(P<0.05);Western blotting结果显示,SAN可通过调控STUB1下游蛋白GPX4的下调(P<0.05)。结论SAN可通过调节STUB1/GPX4诱导结直肠癌细胞发生依赖性铁死亡,提供了新治疗结直肠癌的靶点以及实验依据。 展开更多
关键词 血根碱 结直肠癌 铁死亡 STUB1 GPX4
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血根碱对患者源性结直肠癌类器官生长的影响
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作者 徐志东 周军伟 +7 位作者 倪超 柯希权 马振增 邓晓晶 赵睿 顾林 任志 郑海伦 《中国药理学通报》 CAS CSCD 北大核心 2024年第4期652-661,共10页
目的探讨血根碱(sanguinarine,SNG)对患者源性结直肠癌类器官生长的影响及相关分子机制。方法体外构建结直肠癌类器官,光镜下观察类器官形态变化,HE染色观察肿瘤细胞间结构,免疫组化染色观察肿瘤标志物的表达。用不同浓度的SNG(0.1、0.3... 目的探讨血根碱(sanguinarine,SNG)对患者源性结直肠癌类器官生长的影响及相关分子机制。方法体外构建结直肠癌类器官,光镜下观察类器官形态变化,HE染色观察肿瘤细胞间结构,免疫组化染色观察肿瘤标志物的表达。用不同浓度的SNG(0.1、0.3、1、3、9、27μmol·L^(-1))处理类器官,CCK-8法测细胞活性并计算药物半数抑制浓度(IC 50),Western blot检测SNG对类器官蛋白表达影响,ATP含量检测SNG联合结直肠癌临床化疗药对类器官协同效果。结果48~72 h形成囊样和实质样的三维细胞团,提示类器官构建成功。免疫组化结果,类器官中肿瘤标志物Ki67、CK20、CK7、Ep-CAM表达,进一步证实结直肠癌类器官形成。CCK-8结果显示,相比对照组,SNG组类器官数量和细胞活性降低。Western blot结果显示,p-AMPK表达含量明显上升,而mTOR和p-mTOR表达降低,自噬相关蛋白p62、Beclin1蛋白表达也发生明显变化(P<0.05)。ATP含量检测,SNG与临床化疗药联合抑制结直肠癌细胞的增殖明显强于化疗药单药组(P<0.05)。结论SNG可以抑制结直肠癌类器官生长并诱导自噬,协同化疗药奥沙利铂、伊立替康、5-氟尿嘧啶抑制肿瘤细胞增殖,其作用机制可能与调控AMPK/mTOR信号通路有关。 展开更多
关键词 血根碱 结直肠癌 类器官 AMPK 自噬 临床化疗药
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血根碱通过调控Nrf2/NF-κB通路缓解小鼠溃疡性结肠炎
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作者 赵娜 沈梦迪 +6 位作者 赵睿 奥迪 骆泽谭 张银亮 徐志东 范方田 郑海伦 《南方医科大学学报》 CAS CSCD 北大核心 2024年第8期1467-1475,共9页
目的探讨血根碱(SA)对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)的作用机制。方法随机将56只雄性C57BL/6小鼠分为空白对照组、模型组(DSS组)、SA低剂量组(DSS+SA-L,SA 1 mg/kg)、SA中剂量组(DSS+SA-M,SA 5 mg/kg)、SA高剂量组(DSS+SA-H,... 目的探讨血根碱(SA)对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)的作用机制。方法随机将56只雄性C57BL/6小鼠分为空白对照组、模型组(DSS组)、SA低剂量组(DSS+SA-L,SA 1 mg/kg)、SA中剂量组(DSS+SA-M,SA 5 mg/kg)、SA高剂量组(DSS+SA-H,SA 10 mg/kg)、柳氮磺吡啶组(DSS+SASP,SASP 400 mg/kg)、SA高剂量组+Nrf2抑制剂ML385组(DSS+SA-H+ML385,SA 10 mg/kg+ML38530 mg/kg),8只/组。除空白对照组外,均采用3.5%DSS诱导建立UC模型,SA干预组和柳氮磺吡啶组给与对应药物灌胃治疗,通路抑制剂组SA 10 mg/kg灌胃同时腹腔注射ML38530 mg/kg。通过监测小鼠体质量变化、疾病活动指数(DAI)评分、结肠长度测量、HE染色评估小鼠炎症;检测结肠组织中活性氧(ROS)水平;比色法检测结肠组织中丙二醛含量(MDA);RT-qPCR检测结肠组织中炎性因子;Western blotting法检测结肠组织中核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、Kelch样环氧氯丙烷相关蛋白1(Keap-1)、磷酸化p65蛋白(p-p65)、p65、紧密连接蛋白(occludin、ZO-1)蛋白表达。结果与DSS组相比,SA治疗可缓解DSS组小鼠体质量下降、结肠长度缩短、DAI评分升高(P<0.05)。HE染色显示,DSS组结肠腺体结构破坏,SA可明显改善结肠隐窝结构。RT-qPCR显示,SA干预组结肠组织中TNF-α、IL-1β和IL-6水平下降(P<0.05),ROS、MDA下降(P<0.05)。Western blotting结果显示,结肠组织中Nrf2、HO-1、occludin、ZO-1蛋白表达上升(P<0.05),Keap-1、p-p65蛋白表达下降(P<0.05),p65无明显变化(P>0.05),且DSS+SA-L、DSS+SA-M、DSS+SA-H组各指标变化呈剂量依赖性。Nrf2通路抑制剂ML385降低高剂量组SA对UC小鼠结肠黏膜的改善作用。结论SA可改善UC样小鼠肠炎,作用机制可能与激活Nrf2通路,抑制Nrf2介导的NF-κB通路有关。 展开更多
关键词 溃疡性结肠炎 血根碱 NRF2 NF-ΚB
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基于HPLC检测市售博落回注射液中血根碱和白屈菜红碱的成分含量
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作者 陈思雅 张玮琛 +2 位作者 邱文艳 刘晓轩 杨晶 《饲料研究》 CAS 北大核心 2024年第5期104-108,共5页
试验旨在评估博落回注射剂产品的质量。试验采用高效液相色谱法,建立了博落回注射剂产品中血根碱和白屈菜红碱的同步测定方法。采用Agilent色谱柱,流动相为乙腈-0.1%磷酸,进行梯度洗脱,流速为1.0 mL/min,柱温30℃,检测波长为270 nm,进样... 试验旨在评估博落回注射剂产品的质量。试验采用高效液相色谱法,建立了博落回注射剂产品中血根碱和白屈菜红碱的同步测定方法。采用Agilent色谱柱,流动相为乙腈-0.1%磷酸,进行梯度洗脱,流速为1.0 mL/min,柱温30℃,检测波长为270 nm,进样量5μL。结果显示,博落回注射液中血根碱和白屈菜红碱的HPLC测定方法专属性高,线性范围良好,重复性较好。血根碱和白屈菜红碱精密度RSD分别为0.45%、0.09%,稳定性的RSD分别为0.60%和0.39%,回收率范围分别为99.83%~101.79%、103.47%~105.56%。研究表明,该方法稳定可靠,具有较高的精密度和准确性,可用于评价市售博落回注射液的质量。 展开更多
关键词 博落回注射液 血根碱 白屈菜红碱 HPLC 质量评价
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血根碱在癌症治疗中的抗肿瘤机制研究进展
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作者 冉遥 冷泓旭 +2 位作者 郑凯帆 辛贵忠 濮社班 《中南药学》 CAS 2024年第7期1845-1850,共6页
随着癌症发病率的持续升高,开发新型抗肿瘤药物已成为科研领域的关键方向。血根碱(sanguinarine),一种来源于传统中药如白屈菜(Chelidonium majus L.)、博落回[Macleaya cordata(Willd.)R.Br]、血水草(Eomecon chionantha Hance)和美洲... 随着癌症发病率的持续升高,开发新型抗肿瘤药物已成为科研领域的关键方向。血根碱(sanguinarine),一种来源于传统中药如白屈菜(Chelidonium majus L.)、博落回[Macleaya cordata(Willd.)R.Br]、血水草(Eomecon chionantha Hance)和美洲传统草药血根草(Sanguinaria canadensis L.)等植物的天然生物碱,由于其在抗肿瘤研究中所展现的显著活性,已广受学术界关注。本综述文章旨在梳理血根碱在癌症治疗领域内的研究进展,尤其聚焦其抑制肿瘤增殖、侵袭与转移,并促进肿瘤细胞凋亡的作用机制。研究显示,血根碱通过作用于多条信号传导途径及多种分子靶点,包括Bcl-2、MAPKs、Akt、NF-κB、ROS及微小RNA等,从而发挥其抑制肿瘤的效用。此外,文章还探讨了血根碱针对乳腺癌、肺癌、肝癌及结直肠癌等多种癌症类型的应用研究。据此,开发新的给药策略以提升血根碱的临床应用潜力,成为当前研究的重要课题。未来研究需进一步深化对血根碱抗肿瘤机制的理解,并通过临床前研究及早期临床试验验证其治疗效果与安全性,以期为癌症治疗开辟新路径。 展开更多
关键词 血根碱 抗肿瘤机制 信号通路 药物开发 癌症治疗
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血根碱调节HMGB1/RAGE信号通路对慢性心力衰竭大鼠心肌炎症及细胞凋亡的影响
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作者 张鹏 林桂雄 +4 位作者 卓裕丰 程宏基 陈钦修 谢文杰 冯燕玲 《检验医学与临床》 CAS 2024年第19期2790-2796,共7页
目的探讨血根碱调节高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路对慢性心力衰竭(CHF)大鼠心肌炎症及细胞凋亡的影响。方法通过结扎冠状动脉的左前降支建立CHF大鼠模型,随机分为CHF组、血根碱低剂量组(血根碱-L组,1.0... 目的探讨血根碱调节高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路对慢性心力衰竭(CHF)大鼠心肌炎症及细胞凋亡的影响。方法通过结扎冠状动脉的左前降支建立CHF大鼠模型,随机分为CHF组、血根碱低剂量组(血根碱-L组,1.00 mg/kg血根碱)、血根碱中剂量组(血根碱-M组,2.50 mg/kg血根碱)、血根碱高剂量组(血根碱-H组,6.25 mg/kg血根碱)以及血根碱-H+rHMGB1组(6.25 mg/kg血根碱+8μg/kg rHMGB1),并以仅开胸的正常大鼠作为假手术组,每组10只大鼠。干预结束后,进行超声心动图指标[缩短分数(FS)、左室射血分数(LVEF)、室间隔厚度(IVS)以及舒张末期左心室内径(LVIDD)]检测;称取心脏质量,计算心脏指数;采用酶联免疫吸附试验(ELISA)检测各组血清中白细胞介素(IL)-1β、IL-10、肿瘤坏死因子-α(TNF-α)水平;分别采用苏木精-伊红(HE)染色、缺口末端标记(TUNEL)染色观察心脏组织病理学变化及细胞凋亡变化;采用蛋白质免疫印迹技术检测心脏组织中HMGB1、RAGE蛋白表达。结果与假手术组相比,CHF组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平明显增加(P<0.05),FS、IVS、LVEF及IL-10水平明显降低(P<0.05);与CHF组相比,血根碱不同剂量组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平明显降低(P<0.05),FS、IVS、LVEF及IL-10水平明显增加(P<0.05);在血根碱不同剂量组中,LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平均为血根碱-L组>血根碱-M组>血根碱-H组,FS、IVS、LVEF及IL-10水平均为血根碱-L组<血根碱-M组<血根碱-H组,任意两组间比较,差异均有统计学意义(P<0.05);与血根碱-H组相比,血根碱-H+rHMGB1组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平均明显增加(P<0.05),FS、IVS、LVEF及IL-10水平均明显降低(P<0.05)。结论血根碱可改善CHF大鼠心功能,抑制其心肌炎症及细胞凋亡,以高剂量血根碱效果最佳,可能与调节HMGB1/RAGE信号通路有关。 展开更多
关键词 血根碱 慢性心力衰竭 心肌炎症 细胞凋亡 高迁移率族蛋白B1 晚期糖基化终末产物受体 信号通路
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博落回杀灭鱼类指环虫和病原菌活性成分的研究 被引量:30
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作者 王高学 王建福 +3 位作者 原居林 申烨华 郑伟 李丽 《西北植物学报》 CAS CSCD 北大核心 2007年第8期1650-1655,共6页
采用常压硅胶柱层析和RP-HPLC制备并结合杀虫、抑菌活性追踪的方法,从博落回中分离获得了杀灭金鱼指环虫和抑制鱼类病原菌的活性成分,通过TLC、UV、m.p.、IR、MS、1H NMR和13C NMR鉴定其为血根碱.杀灭指环虫试验结果表明:血根碱对指环... 采用常压硅胶柱层析和RP-HPLC制备并结合杀虫、抑菌活性追踪的方法,从博落回中分离获得了杀灭金鱼指环虫和抑制鱼类病原菌的活性成分,通过TLC、UV、m.p.、IR、MS、1H NMR和13C NMR鉴定其为血根碱.杀灭指环虫试验结果表明:血根碱对指环虫有较强杀灭活性,在质量浓度为0.6 mg?L-1时的杀虫率达到100%.血根碱对6株水产致病菌的活性试验结果表明:对嗜水气单胞菌的活性最高,MIC和MBC分别为12.5和25μg·mL-1;对哈维弧菌、鳗弧菌、杀鲑气单胞菌史氏亚种的活性最弱,其MIC和MBC均分别为50和100μg·mL-1.血根碱杀灭鱼类指环虫活性较高,对6株水产病原菌都有明显抑制作用. 展开更多
关键词 博落回 血根碱 指环虫 病原菌 活性
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