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| 1 | 从白屈菜乙醇提取物中分离出的白屈菜碱通过p38-p53和PI3K/AKT信号转导通路促进 HeLa细胞凋亡(英文)显示文摘目的:研究从白屈菜乙醇提取物中分离出的白屈菜碱在诱导 HeLa细胞凋亡中的作用及参与其作用的主要信号转导通路。方法:细胞先以不同浓度白屈菜碱处理48h,用噻唑蓝法分析确定半数致死量(median lethal dose,LD50)。用4′,6-二脒基-2-苯基吲哚染色,追踪分析核浓染以及 DNA 损伤和碎片的形态学变化,并用流式细胞术分析检测活性氧(reactive oxygen species,ROS)的产生以及细胞周期阻滞和线粒体膜电位的变化。用圆二色光谱分析寻找白屈菜碱和小牛胸腺 DNA可能的相互作用。用逆转录聚合酶链反应和蛋白免疫印迹法测定p38、p53、蛋白激酶B(protein kinase B,AKT)、磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinases,PI3K)、Janus激酶3(Janus kinase 3,JAK3)、信号转导及转录激活因子3(signal transducer and activator oftranscription 3,STAT3)等的mRNA和蛋白表达,以及E6、E7癌基因和促凋亡基因、抗凋亡基因的mRNA和蛋白表达。结果:根据白屈菜碱的LD50(30μg/mL),选定3种实验剂量,即22.5、30和37.5μg/mL。结果显示,白屈菜碱抑制了 HeLa细胞增殖,诱发其细胞凋亡,表现为 ROS的产生,细胞亚 G1和 G0/G1周期阻滞,线粒体膜电位变化和 DNA 碎片产生。圆二色光谱分析结果显示白屈菜碱和小牛胸腺 DNA 间存在有效的相互作用。信号通路的研究显示白屈菜碱通过上调p38、p53和其他促凋亡基因的表达,以及下调 AKT、PI3K、JAK3、STAT3、E6、E7和其他抗凋亡基因的表达,有效诱发细胞凋亡。结论:从白屈菜中分离出的白屈菜碱能通过改变p38-p53及 AKT/PI3激酶信号转导通路有效地诱发 HeLa细胞凋亡。 | Avijit Paul Kausik Bishayee Samrat Ghosh Avinaba Mukherjee Sourav Sikdar Debrup Chakraborty Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2012 | 中西医结合学报2012，10，9： | 10 |
| 2 | 东莨菪亭(7-羟基-6-甲氧基香豆素)对7 ,12-二甲基苯并蒽诱导的皮肤乳头状瘤小鼠相关关键信号蛋白的影响(英文)显示文摘目的:东莨菪亭(7-羟基-6-甲氧基香豆素)是从常绿钩吻中提取的有效成分,前期体外研究证实了其抗肿瘤潜能,本研究评价其在小鼠体内的抗肿瘤作用。方法:30只健康小鼠随机分为正常对照组、模型组、溶剂对照组和低、高剂量东莨菪亭组,每组6只。正常对照组小鼠不接受任何干预,其余小鼠背部涂抹100μg 7 ,12-二甲基苯并蒽(7 ,12-di methylbenz[a]anthra-cene ,DMBA)(每周一次)和1 %巴豆油(每周2次)诱导皮肤乳头状瘤,共24周。溶剂组小鼠在造模基础上每天予2 %酒精口服,低剂量(50 mg/kg)和高剂量(100 mg/kg)东莨菪亭组小鼠每天予东莨菪亭治疗。治疗24周后,检测碱性磷酸酶、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶活性;信号蛋白及其受体,包括芳香烃受体(Aryl hydrocarbon receptor , AhR)、p53、细胞色素P450亚酶1A1(cytochrome P450 1A1 , CYP1A1)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、信号转导和转录激活因子3(signal transducer and activator of transcription-3 ,Stat-3)、存活素、金属基质蛋白酶2、cyclin D1、c-myc、金属蛋白酶组织抑制因子2和半胱氨酸蛋白酶3(caspase-3) ,采用逆转录聚合酶链反应、蛋白印迹法或免疫沉淀法检测。结果:致癌物DMBA和巴豆油可以诱导毒性反应,生化指标中相关酶活性升高,AhR、CYP1A1、PCNA、Stat-3、存活素、MMP-2、cyclin D1和c-myc表达上调,p53、caspase-3和TI MP-2表达下调。荷瘤小鼠采用东莨菪亭治疗后,生化指标中相关酶的活性下降,蛋白表达和毒性生物标志物恢复正常。结论:东莨菪亭可能通过下调AhR表达来下调一些重要信号蛋白的表达,其作用机制可能是通过竞争性抑制存活素的表达。分裂原活化蛋白激酶可能也起到关键作用。东莨菪亭或许可作为化疗的替代药物用于治疗肿瘤。 | Soumya Sundar Bhattacharyya Saili Paul Suman Dutta Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2010 | 中西医结合学报2010，8，7： | 7 |
| 3 | 5-Lipoxygenase Antagonist therapy: a new approach towards targeted cancer chemotherapy显示文摘Leukotrienes 是丰满的酸的 bioactive 组和酸新陈代谢由 5-lipoxygenase (5 哈鱼) 的催化活动塑造了的 arachidonic 的主要成分。证据包括前列腺,肺,结肠,和 colorectal 癌症在癌症的不同类型的前进在 5 哈鱼的直接参与的支持正在积累。几独立研究现在支持在生存能力,增长,房间迁居,通过细胞外的矩阵破坏的侵略,转移,和 anti-apoptotic 发信号的激活串联的 5 哈鱼表示和癌症房间之间的关联。表皮的生长因素受体和 5-oxo-ETE 受体(OXER1 ) 的参与是主要谈话点在 5 哈鱼小径下游,它联系癌症细胞到 proliferative 小径。指向到 5 哈鱼,拍动(5-LOX-activating 蛋白质) ,和 OXER1 的 blocker 的不同类型的 Antisense 技术途径和使用在与不同癌症房间类型作斗争显示出更大的效率。最后,减少房间增长活动的 5 哈鱼活动的抑制也以 p53 依赖或独立的方式导致内在的 mitochondrial apoptotic 小径。明确地禁止调停哈鱼的发信号小径的药理学代理人在最后几年期间被使用了治疗象气喘和关节炎那样的煽动性的疾病。这些描绘得好的代理人的研究因此对致命的疾病癌症作为化学疗法的研究的可能的候选人为他们的使用被保证。 | Kausik Bishayee Anisur Rahman Khuda-Bukhsh | 2013 | Acta Biochimica et Biophysica Sinica2013，45，9： | 6 |
| 4 | 天然植物化学成分东莨菪亭聚合物纳米胶囊的制备及其对人黑色素瘤A375细胞的作用(英文)显示文摘目的:东莨菪亭(7-羟基-6甲氧基香豆素,化学式C10H8O4,简称HMC)是从常绿钩吻(Gelsemium sem pervirens)中提取的一种天然香豆素类化合物,被认为具有抗癌活性。本研究将HMC制成聚乳酸聚乙醇酸共聚物(polylactic-co-glycolic acid,PLGA)纳米颗粒胶囊,通过多项指标观察其与非纳米HMC相比,在被细胞摄取、生物利用度及对细胞凋亡的影响(抗癌活性)等方面是否有所提高。方法:人黑色素瘤A375细胞用来检测HMC及纳米HMC颗粒(nano-7-hydroxy-6-methoxy coumarin,NHMC)的被细胞摄取率及抗癌活性;通过动态光散射确定NHMC的颗粒大小、多分散性指数及电动电位;扫描电子显微镜及原子力显微镜检测纳米颗粒的表面形态。结果:HMC制成纳米颗粒胶囊的包封率超过85%。NHMC颗粒的平均直径小于110nm,其多分散性系数为0.237,提高了其被细胞摄取率及生物活性。NHMC被细胞摄取的时间(15min)明显少于非纳米HMC(30min)。测定细胞内某些信号分子mRNA的表达,表明NHMC作用细胞后能够下调细胞周期素D1(cyclin-D1)、增殖细胞核抗原(PCNA)、存活素(survivin)及信号转导和转录活化因子3(Stat-3)的表达并上调p53及半胱天冬酶3(caspase-3)的表达。与非纳米HMC相比,NHMC能够更快地被细胞摄取并引起更多的肿瘤细胞凋亡。NHMC对正常皮肤细胞无明显细胞毒性。结论:使用生物可降解材料PLGA制成的小分子纳米颗粒NHMC能够更快速地被细胞摄取并引起更多的肿瘤细胞凋亡,而对正常皮肤细胞无明显细胞毒性。提取天然药用植物中的有效成分制成纳米颗粒胶囊有望成为更好地发挥其药效的途径。 | Anisur Rahman Khuda-Bukhsh Soumya Sundar Bhattacharyya Saili Paul Naoual Boujedaini | 2010 | 中西医结合学报2010，8，9： | 6 |
| 5 | A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase Ⅱ activities as also by promoting apoptosis via intrinsic mitochondrial pathway显示文摘OBJECTIVE: Homeopathic nosodes have seldom been scientifically validated for their anticancer effects. This study was conducted to examine if a recently developed hepatitis C nosode has demonstrable anticancer potential in cancer cells in vitro.METHODS: Anticancer effects of Hepatitis C 30C(Hep C 30), if any, were initially tested on three cancer cell lines, HepG2(liver cancer), MCF-7(breast cancer) and A549(lung cancer) and one normal liver cell line WRL-68 cells and subsequently a more thorough study using further scientific protocols was undertaken on HepG2 cells(against WRL-68 cells as the normal control) as HepG2 cells showed better anticancer response than the other two. Three doses, one at 50% lethal dose(LD_(50)) and the other two below LD_(50), were used on HepG2 cells subsequently. Protocols like apoptosis induction and its possible signaling mechanism were deployed using immunoblots of relevant signal proteins and confocal microscopy, with particular reference to telomerase and topoisomerase Ⅱ(Top Ⅱ) activities, two strong cancer biomarkers for their direct relationship with divisional activities of cells and DNAs. RESULTS: Hep C 30 induced apoptosis, caused distorted cell morphology typical of apoptotic cells, increased reactive oxygen species generation and produced increased DNA nicks. Further it enhanced pro-apototic signal proteins like Bax, cytochrome c and inhibited anti-apoptotic signal proteins, Bcl-2, cytochrome c and caspase-3, changed mitochondrial membrane potential and caused externalization of phosphatidylserine. The drug also decreased expression of two cancer biomarkers, Top Ⅱ and telomerase, consistent with its anticancer effect. CONCLUSION: Hep C 30 has demonstrable anticancer effects against liver cancer cells in vitro. | Jesmin Mondal Jayeeta Das Rajesh Shah Anisur Rahman Khuda-Bukhsh | 2016 | Journal of Integrative Medicine2016，14，3： | 5 |
| 6 | Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase-mediated signaling via reactive oxygen species elevation显示文摘OBJECTIVE: Preventive measures against skin melanoma like chemotherapy are useful but suffer from chronic side effects and drug resistance. Ethanolic extract of Phytolacca decandra (PD), used in homeopathy for the treatment of various ailments like chronic rheumatism, regular conjunctivitis, psoriasis, and in some skin diseases was tested for its possible anticancer potential. METHODS: Cytotoxicity of the drug was tested by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on both normal (peripheral blood mononuclear cells) and A375 cells. Fluorescence microscopic study of 4',6-diamidino-2-phenylindole dihydrochloride-stained cells was conducted for DNA fragmentation assay, and changes in cellular morphology, if any, were also recorded. Lactate dehydrogenase activity assay was done to evaluate the percentages of apoptosis and necrosis. Reactive oxygen species (ROS) accumulation, if any, and expression study of apoptotic genes also were evaluated to pin-point the actual events of apoptosis. RESULTS: Results showed that PD administration caused a remarkable reduction in proliferation of A375 cells, without showing much cytotoxicity on peripheral blood mononuclear cells. Generation of ROS and DNA damage, which made the cancer cells prone to apoptosis, were found to be enhanced in PD-treated cells. These results were duly supported by the analytical data on expression of different cellular and nuclear proteins, as for example, by down-regulation of Akt and Bcl-2, up-regulation of p53, Bax and caspase 3, and an increase in number of cell deaths by apoptosis in A375 cells. CONCLUSION: Overall results demonstrate anticancer potentials of PD on A375 cells through activation of caspase-mediated signaling and ROS generation. | Samrat Ghosh Kausik Bishayee Avijit Paul Avinaba Mukherjee Sourav Sikdar Debrup Chakraborty Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2013 | Journal of Integrative Medicine2013，11，2： | 5 |
| 7 | 美洲远志根提取物对苯并芘致肺癌小鼠的抗肿瘤作用(英文)显示文摘目的:研究美洲远志(Polygala senega)根的乙醇提取物对苯并芘致肺癌小鼠的抗肿瘤作用。方法:瑞士白化小鼠被分为5组,每组6只。组1为对照组,予口服橄榄油;组2予苯并芘(50mg/kg体质量,溶于橄榄油中),每周2次,连续4周;组3除予与组2相同的苯并芘外,再予48%乙醇;组4予与组2相同的苯并芘,并同时给予美洲远志的乙醇提取物,每日1次,连续16周;组5仅给予美洲远志的乙醇提取物,每日1次,连续16周。16周后,处死所有小鼠并检测和评价以下指标:2,2-二苯基-1-苦基肼(2,2-diphenyl-1-picrylhydrazyl,DPPH)法测定美洲远志乙醇提取物的抗氧化功效;分别称取各组小鼠的肺组织质量及体质量;彗星实验及酶联免疫吸附法检测DNA损伤情况;分别测定过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、脂质过氧化反应及总含硫化合物含量。结果:给予美洲远志乙醇提取物治疗的组4小鼠与组3模型组小鼠相比,体质量明显增加而肺组织质量明显降低(P<0.01)。彗星实验结果显示组4小鼠的DNA损伤较组3小鼠明显减轻(P<0.01)。酶联免疫吸附法测定p53蛋白水平,组4明显高于组3(P<0.01)。组2和组3的模型小鼠与组1比较,脂质过氧化反应水平明显升高,而抗氧化标志物的水平明显降低(P<0.05),组4小鼠的这些指标被明显逆转(P<0.01)。结论:美洲远志对于化学制剂致小鼠肺癌有明确的治疗效果。 | Saili Paul Soumya Sundar Bhattacharyya Asmita Samaddar Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2011 | 中西医结合学报2011，9，3： | 4 |
| 8 | Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines:signalling pathway and drug-DNA interaction显示文摘OBJECTIVE:To test if myricanone(C_(21)H_(24)O_5),a cyclic diarylheptanoid,has anticancer effects on two different cancer cell lines HeLa and PC3.The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway.METHODS:Several studies like cytotoxicity,nuclear damage,annexin-V-fluorescein isothiocyanate(FITC)/propidium iodide(Pl)-labelled apoptotic assay and cell cycle arrest,immunoblot and reverse transcriptase-polymerase chain reaction(RT-PCR)were used following standard protocols.Circular dichroism(CD)spectroscopy was also done to evaluate whether myricanone effectively interacted with DNA to bring about conformational changes that could strongly inhibit the cancer cell proliferation.RESULTS:Myricanone showed a greater cytotoxic effect on PC3 cells than on HeLa cells.Myricanone promoted G_0/G_1 arrest in HeLa cells and S phase arrest in PC3 cells.Nuclear condensation and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell death.CD spectroscopic data indicated that myricanone had an interaction with calf thymus DNA that changed DNA structural conformation.RT-PCR and immunoblot studies revealed that myricanone activated the apoptotic signalling cascades through down-regulation of transcription factors like nuclear factor-κB(NF-κB)(p65),and signal transducers and activators of transcription 3(STAT3);cell cycle regulators like cyclin D1,and survivin and other signal proteins like Bcl-2 and up-regulation of Bax,caspase-9 and caspase-3.CONCLUSION:Myricanone induced apoptosis in both types of cancer cells by triggering caspase activation,and suppression of cell proliferation by down-regulation of NF-κB and STAT3signalling cascades,which makes it a suitable candidate for possible use in the formulation of therapeutic agent for combating cancer. | Avijit Paul Sreemanti Das Jayeeta Das Asmita Samadder Kausik Bishayee Ratan Sadhukhan Anisur Rahman Khuda-Bukhsh | 2013 | Journal of Integrative Medicine2013，11，6： | 4 |
| 9 | Non-invasive diagnosis of H pylori infection: Evaluation of serological tests with and without current infection marker CIM显示文摘AIM:To evaluate the performance of commercially available immunochromatographic (ICT) and immunoblot tests covering the current infection marker CIM and conventional ELISA for the diagnosis of H pylori infection in adult dyspeptic patients. METHODS:Consecutive non-treated dyspeptic patients undergoing diagnostic endoscopy were tested for H pylori infection by culture, rapid urease test, and histology of gastric biopsy specimens. Serum from 61 H pylori infected and 21 non-infected patients were tested for anti-H pylori IgG antibodies by commercial ELISA (AccuBindTM ELISA, Monobind, USA), ICT (Assure H pylori Rapid Test, Genelabs Diagnostics, Singapore), and immunoblot (Helico Blot 2.1, Genelabs Diagnostics, Singapore) assays. ICT and immunoblot kits cover CIM among other parameters and their performance with and without CIM was evaluated separately. RESULTS:Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ELISA were 96.7%, 42.8%, 83.1%, 81.8%, and 82.9%, of ICT were 90.1%, 80.9%, 93.2%, 73.9%, and 87.8%, of ICT with CIM were 88.5%, 90.4%, 96.4%, 73.0%, and 89.0%, of immunoblot were 98.3%, 80.9%, 93.7%, 94.4%, and 93.9%, and of immunoblot with CIM were 98.3%, 90.4%, 96.7%, 95.0%, and 96.3%, respectively. CONCLUSION:Immunoblot with CIM had the best performance. ICT with CIM was found to be more specific and accurate than the conventional ELISA and may be useful for non-invasive diagnosis of H pylori infection. | Sufi HZ Rahman M Golam Azam M Anisur Rahman MS Arfin M Mahbub Alam Tareq M Bhuiyan Nasim Ahmed Motiur Rahman Shamsun Nahar MS Hassan | 2008 | World Journal of Gastroenterology2008，14，8： | 4 |
| 10 | 高度稀释的葡萄糖溶液提高含亚砷酸盐培养基中大肠埃希氏杆菌的葡萄糖摄取(英文)显示文摘目的:高度稀释的顺势疗法药物对活体系统的作用一直被质疑。因此,本研究检测依据顺势医学理论而高度稀释的葡萄糖溶液对暴露于亚砷酸盐的大肠埃希氏杆菌的作用。方法:大肠埃希氏杆菌在Luria-Bertani培养基中培养至对数期后分组。分别加入1%或3%的葡萄糖溶液、葡萄糖30C(在70%乙醇中稀释1060倍)、1mmol/L或2mmol/L的亚砷酸钠、1mmol/L或2mmol/L的亚砷酸钠加葡萄糖30C、1mmol/L或2mmol/L的亚砷酸钠加乙醇30C(安慰剂)。分析用药后45min及90min大肠埃希氏杆菌的葡萄糖摄取、己糖激酶及葡糖激酶活性、细胞膜电位、细胞内三磷酸腺苷含量以及葡萄糖通透酶基因的表达情况,并测定细胞内及细胞外(培养基内)亚砷酸盐的浓度。结果:暴露于亚砷酸盐的大肠埃希氏杆菌的葡萄糖摄取量增加,己糖激酶及葡糖激酶活性、细胞内三磷酸腺苷含量及细胞膜电位降低,葡萄糖通透酶基因的表达增加。在加入1%或3%葡萄糖或高度稀释的葡萄糖30C的培养基内,大肠埃希氏杆菌的葡萄糖摄取量进一步增加,而在加入乙醇30C(安慰剂)的培养基内,大肠埃希氏杆菌的葡萄糖摄取量没有明显增加。结论:本研究的结果证实了高度稀释的葡萄糖溶液对于真正的葡萄糖溶液的模仿作用。这种顺势疗法理论下高度稀释的葡萄糖溶液能够调节大肠埃希氏杆菌己糖激酶和葡糖激酶的表达以及葡萄糖通透酶基因的表达,证实了顺势疗法中高度稀释的药物的有效性。 | Anisur Rahman Khuda-Bukhsh Arnab De Durba Das Suman Dutta Naoual Boujedaini | 2011 | 中西医结合学报2011，9，8： | 3 |
| 11 | 顺势疗法药物山金车30C通过上调核苷酸切除修复基因的表达减少紫外线照射后大肠杆菌的DNA损伤(英文)显示文摘目的:检测高度稀释的顺势疗法药物山金车30C是否能够调节暴露于紫外线照射下的大肠杆菌的核苷酸切除修复基因的表达。方法:大肠杆菌在标准培养基中培养至对数阶段,然后接受亚致死剂量的紫外线照射(25和50 J/m2分别照射22.5和45 s)。接受不同剂量紫外线照射的大肠杆菌分别与山金车30C及安慰剂30C共同培养,90 min后检测其DNA损伤情况及氧化应激状态。采用多种方法及指标如彗星实验、梯度凝胶电泳、细胞内活性氧生成及测量其他生物活性指标如过氧化物歧化酶、过氧化氢酶及谷胱甘肽衡量DNA损伤情况及细胞氧化应激状态。逆转录聚合酶链反应检测大肠杆菌细胞紫外线损伤修复基因uvrA、B、C(核苷酸切除修复基因)mRNA的表达情况。结果:接受照射后的大肠杆菌出现了DNA损伤及氧化应激反应,表现为细胞内活性氧生成增加及过氧化物歧化酶、过氧化氢酶和谷胱甘肽活性降低。与安慰剂组相比,山金车30C降低了大肠杆菌的DNA损伤及氧化应激反应,表现为细胞内活性氧生成减少及过氧化物歧化酶、过氧化氢酶和谷胱甘肽活性增强。与对照组相比,山金车30C上调了大肠杆菌细胞紫外线损伤修复基因的表达。结论:山金车30C能够通过上调紫外线损伤修复基因的表达修复紫外线引起的大肠杆菌细胞的DNA损伤,并通过减少细胞内活性氧的生成及调节抗氧化酶活性降低细胞的氧化应激反应。 | Sreemanti Das Santu Kumar Saha Arnab De Durba Das Anisur Rahman Khuda-Bukhsh | 2012 | 中西医结合学报2012，10，3： | 3 |
| 12 | Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling cascade显示文摘OBJECTIVE: Oleanolic acid(OA) has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation.METHODS: Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor(EGFR) activity were performed. To investigate whether cells undergo apoptosis, studies like fl uorescence microscopy, poly(ADP-ribose) polymerase(PARP) degradation, annexin V-fl uorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed.RESULTS: OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells(skin keratinocytes) and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an antiproliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondriadependent caspase 3-mediated apoptosis.CONCLUSION: OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent. | Samrat Ghosh Kausik Bishayee Anisur Rahman Khuda-Bukhsh | 2014 | Journal of Integrative Medicine2014，12，2： | 3 |
| 13 | 北美香柏叶的乙醇提取物阻断A549细胞增殖并引起细胞凋亡的体外研究(英文)显示文摘目的:研究北美香柏叶的乙醇提取物对非小细胞肺癌A549细胞的抗肿瘤及抗增殖作用。方法:噻唑蓝法检验不同剂量北美香柏叶的乙醇提取物对细胞活性的影响。确定半数最大抑制浓度为282μg/mL,另外选择两个浓度188μg/mL和376μg/mL进行剂量依赖性检测。进行溴脱氧尿苷结合实验和细胞迁移实验检测药物的抗肿瘤细胞增殖活性。膜联蛋白V-异硫氰酸荧光黄-碘化丙啶双染色后采用荧光激活细胞分类分析仪对细胞早期凋亡进行检测。Hoechst 33258及吖啶橙-溴化乙啶荧光染色法进行DNA片段分析。间接酶联免疫吸附法分析Bax-Bcl2的调节和表达情况。逆转录聚合酶链反应检测caspase3基因表达情况,其活性和蛋白水平的表达则使用间接酶联免疫吸附法和蛋白印迹法进行检测。结果:A549的细胞活性在暴露于北美香柏叶的乙醇提取物24h后呈剂量依赖性下降。脱氧尿苷结合实验和细胞迁移实验表明细胞的增殖活性与暴露于药物的时间有时间依赖性关系。11.72%的细胞在双染色后呈阳性反应,表明药物引起了细胞的早期凋亡。药物作用24h后DNA片段彗星尾的出现以及Hoechst 33258荧光染色的增加提示显著的DNA缺口出现以及染色质凝聚。Bax的上调及Bcl2的下调表明了细胞凋亡的出现。逆转录聚合酶链反应、间接酶联免疫吸附法以及蛋白印迹法的检测结果表明caspase3的活性随着抗聚(腺苷二磷酸-核糖)聚合酶的表达的增加而增加。结论:北美香柏叶的乙醇提取物能够促进A549细胞凋亡并抑制其增殖活性。 | Avinaba Mukherjee Sourav Sikdar Kausik Bishayee Avijit Paul Samrat Ghosh Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2012 | 中西医结合学报2012，10，12： | 2 |
| 14 | 顺势疗法药物白砷剂抑制暴露于三氧化二砷的大肠杆菌细胞内活性氧的产生并上调其抗三氧化二砷基因的表达(英文)显示文摘目的:检验顺势疗法药物Arsenicum Album 30C(Ars Alb 30C)是否能够降低亚砷酸钠对大肠杆菌(Escherichiacoli)的毒性。方法:将在标准培养基中培养至对数生长期的大肠杆菌暴露于低剂量砷剂下。1或2 mmol/L亚砷酸钠单独作用于大肠杆菌作为对照,在此基础上加入Ars Alb 30C作为治疗组,或加入按顺势疗法原则配置的乙醇作为安慰剂组。分别于45 min和90 min后检测大肠杆菌的葡萄糖摄取量,细胞内己糖激酶、脂质过氧化物酶、超氧化物歧化酶及过氧化氢酶活性,细胞内外亚砷酸钠含量,细胞生长情况,细胞膜电位,DNA损伤情况,细胞内活性氧、三磷酸腺苷及自由型谷胱甘肽含量,以及arsB和ptsG基因表达情况。实验按照随机分组原则及盲法原则进行。结果:暴露于亚砷酸钠的大肠杆菌的葡萄糖摄取量、细胞内活性氧、脂质过氧化反应及DNA损伤增加;己糖激酶、超氧化物歧化酶及过氧化氢酶活性降低;细胞内三磷酸腺苷及自由型谷胱甘肽含量降低;细胞膜电位降低且细胞生长缓慢;arsB和ptsG基因表达水平增高。Ars Alb 30C作用后降低了亚砷酸钠对大肠杆菌的毒性,表现为抑制细胞内活性氧的生成和对细胞生长的促进作用。结论:Ars Alb 30C能够降低亚砷酸钠对大肠杆菌的毒性,证实了这一顺势疗法原则下高度稀释的药物的效用。 | Arnab De Durba Das Suman Dutta Debrup Chakraborty Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2012 | 中西医结合学报2012，10，2： | 2 |
| 15 | 海南蒲桃提取物对L6细胞砷中毒缓解作用的体外实验(英文)显示文摘目的:研究海南蒲桃提取物对砷酸盐引起的L6骨骼肌细胞葡萄糖内稳态破坏及线粒体功能异常的缓解作用。方法:通过测量多个指标如丙酮酸激酶活性、葡糖激酶、线粒体膜电位等衡量细胞内葡萄糖水平及线粒体功能,并测量相关标志物的蛋白质及mRNA表达情况,如葡萄糖转运体4、胰岛素受体基质1、胰岛素受体基质2、葡糖激酶等以分析可能有关的信号通路。结果:海南蒲桃提取物能够通过葡萄糖转运体4通路改善砷中毒的L6细胞内诸多标志物的表达,使其正常化,与模型组相比差异有统计学意义。结论:海南蒲桃提取物对细胞砷中毒有明显的缓解作用,未来可考虑将其用于治疗砷中毒相关疾病如高血糖症等。 | Asmita Samadder Jayeeta Das Sreemanti Das Raktim Biswas Anisur Rahman Khuda-Bukhsh | 2012 | 中西医结合学报2012，10，11： | 2 |
| 16 | Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro显示文摘OBJECTIVE: Methylation-specifi c epigenetic process and gene expression profi les of He La cells treated with ultra-high dilutions(HDs) of two plant extracts, Hydrastis canadensis(HC-30) and Marsdenia condurango(Condu-30), diluted 1060 times, were analyzed against placebo 30C(Pl-30) for alterations in gene profi les linked to epigenetic modifi cations.METHODS: Separate groups of cells were subjected to treatment of Condu-30, HC-30, and Pl-30 prepared by serial dilutions and succussions. Global microarray data recorded on Affymetrix platform, using 25-mer probes were provided by i Life Discoveries, India. Slides were scanned with 3000 7G microarray scanner and raw data sets were extracted from Cel(raw intensity) fi les. Analyses of global microarray data profi le, differential gene expression, fold change and clusters were made using Gene Spring GX12.5 software and standard normalization procedure. Before microarray study, concentration of RNA(ng/μL), RIN value and r RNA ratio for all the samples were analysed by Agilant Bioanalyzer 2100. Reverse transcriptase polymerase chain reaction(RT-PCR) and quantitative RTPCR were done for analyzing SMAD-4 expression. Fluorescence-activated cell sorting study was further made to elucidate fate of cells at divisional stages. Methylation-specifi c restriction enzyme assay was conducted for ascertaining methylation status of DNA at specifi c sites.RESULTS: HDs of HC-30 and Condu-30 differentially altered methylation in specifi c regions of DNA and expression profi les of certain genes linked to carcinogenesis, as compared to Pl-30. Two separate cut sites were found in genomic DNA of untreated and placebo-treated He La cells when digested with McrB C, compared to a single cut observed in Condu-30-treated genomic DNA. SMAD-4 gene expression validated the expression pattern observed in microarray profi le. Methylation-specifi c restriction enzyme assay elucidated differential epigenetic modifi cations in drug-treated and control cells.CONCLUSION: HDs triggered epigenetic modifi cations and alterations in microarray gene expression profi les of many genes associated with carcinogenesis in HeLa cells in vitro. | Santu Kumar Saha Sourav Roy Anisur Rahman Khud a-Bukhsh | 2015 | Journal of Integrative Medicine2015，13，6： | 2 |
| 17 | 顺势疗法药物白砷剂对暴露于砷的酵母菌的蛋白标志物及基因表达的影响(英文)显示文摘目的:本研究旨在证实顺势疗法药物Arsenicum Album30C(Ars Alb30C)是否能够改善暴露于砷酸盐的酵母菌(Saccharomyces cerevisiae)的各项生化指标及是否影响其DNA的合成。方法:标准培养基上的酵母菌暴露于最终浓度为0.15mmol/L的砷酸盐试剂中分别1h和2h后,检测细胞活力及其他生物活性指标如过氧化氢酶、超氧化物歧化酶、总硫醇、葡萄糖-6-磷酸脱氢酶、脂质过氧化反应、蛋白羰基化反应及DNA损伤情况,并对活性氧聚集情况、其他相关的应激转录激活因子如Yap-1和Msn2的表达以及酵母细胞凋亡蛋白酶-1进行检测。结果:暴露于砷酸盐中的酵母菌,其脂质过氧化反应、蛋白羰基化反应、DNA损伤、活性氧聚集及Yap-1、Msn2和酵母细胞凋亡蛋白酶-1的表达均有所升高,而过氧化氢酶、超氧化物歧化酶、总硫醇及葡萄糖-6-磷酸脱氢酶的水平均有所降低。与对照组比较,与Ars Alb30C共培养的细胞以上指标均有明显改善(P<0.05),只有Yap-1的表达未见明显降低。结论:顺势疗法药物Ars Alb30C能够激活暴露于砷酸盐的酵母菌的自我调节能力。 | Durba Das Arnab De Suman Dutta Raktim Biswas Naoual Boujedaini Anisur Rahman Khuda-Bukhsh | 2011 | 中西医结合学报2011，9，7： | 2 |
| 18 | Evaluation of chemopreventive potentials of ethanolic extract of Ruta graveolens against A375 skin melanoma cells in vitro and induced skin cancer in mice in vivo显示文摘OBJECTIVE: Chemopreventive approach with natural products, particularly plants and plant-derived ones, is receiving increasing attention for their effective role against cancer without any palpable side effects. In this study, efficacy of ethanolic extract of Ruta graveolens(RG) on skin melanoma cells(A375) in vitro and on 7,12-dimethylbenz(a)anthracene(DMBA)-induced skin cancer in vivo has been tested in Swiss albino mice.METHODS: Studies on cell viability, apoptosis and autophagy induction were conducted in vitro. To check apoptosis, assays like alteration in mitochondrial membrane potential, annexin V-fluorescein isothiocyanate/propidium iodide assay and immunoblot were performed. Fluorescence microscopic and immunoblot assays were performed to confirm autophagy induction. The effects of RG were determined by evaluating body weight, tumor incidence, tumor volume and tumor burden in mice. Enzymatic and non-enzymatic antioxidant status was assessed. The role of some relevant signaling proteins was also analyzed.RESULTS: RG caused death of A375 cells through induction of caspase 3-mediated apoptosis and Beclin-1-associated autophagy. Moreover, RG administration(75 mg/kg body weight) which showed no acute or chronic toxicity, showed significant reduction in the skin tumor burden of DMBA-painted mice. RG also demonstrated potent anti-lipid peroxidative and antioxidant functions during the course of skin cancer induction by DMBA.CONCLUSION: Chemopreventive potential of RG was demonstrated from overall results of this study, indicating its possible use in therapeutic formulation of an effective drug to treat skin cancer. | Samrat Ghosh Sourav Sikdar Avinaba Mukherjee Anisur Rahman Khuda-Bukhsh | 2015 | Journal of Integrative Medicine2015，13，1： | 2 |
| 19 | Amelioration of Carcinogen-Induced Toxicity in Mice by Administration of a Potentized Homeopathic Drug, Natrum Sulphuricum 200显示文摘 | Nandini Bhattacharjee Surajit Pathak Anisur Rahman Khuda-Bukhsh | 2007 | Evidence-Based Complementary and Alternative Medicine2007，，1： | 1 |
| 20 | Low doses of ethanolic extract of Boldo(Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro显示文摘OBJECTIVE: Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo(Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin's cytotoxicity without affecting its anticancer potential. METHODS: The cytotoxicity of Boldo extract(BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines(A549, HeLa, and HepG2) and in normal liver cells(WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species(ROS) and mitochondrial membrane potential(MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS: Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drugDNA interaction study revealed that BE reduced cisplatin's DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION: Results indicated that a low dose of BE could be used benefi cially in combination with cisplatin to reduce its toxicity without hampering cisplatin's anticancer effect. These fi ndings signify a potential future use of BE in cancer therapy. | Jesmin Mondal Kausik Bishayee Ashis Kumar Panigrahi Anisur Rahman Khuda-Bukhsh | 2014 | Journal of Integrative Medicine2014，12，5： | 1 |
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