姜黄素衍生物的药理活性及构效关系研究进展

姜黄素具有抗肿瘤、抗炎、抗氧化、抗抑郁和抑制组织因子等多种药理作用.本文综述了近几年姜黄素衍生物药理活性的研究现状,论述了姜黄素及其衍生物的结构与其抗氧化、抗炎和抗肿瘤的药理作用的关系,为姜黄素的开发利用提供基础.     

姜黄素衍生物在体外的抗肿瘤实验

目的研究姜黄素衍生物对不同肿瘤细胞株生长的影响。方法利用体外细胞培养模型,应用MTT法分析姜黄素衍生物对不同肿瘤细胞生长的影响。结果姜黄素衍生物对不同肿瘤细胞生长有一定的抑制作用,且具有剂量依赖性,但较姜黄素的抑制效应弱。结论姜黄素衍生物对不同肿瘤细胞生长具有抑制作用。     

姜黄素衍生物对人白血病细胞株HL-60增殖的抑制作用及初步机制探讨

目的对姜黄素进行了相应的修饰得到了二十五个姜黄素衍生物,并在细胞水平对这些化合物的体外抗肿瘤活性及其机制进行初步探讨。方法采用MTT法研究姜黄衍生物(6.25μM、12.5μM、25μM和50μM)在体外对HL-60的成活率的影响,并采用吖啶橙(AO)/溴化乙锭(EB)荧光双染法染色及流式细胞术对其作用机制进行了初步探讨。结果MTT实验结果表明姜黄素衍生物对人白血病细胞株HL-60的存活率具有一定的影响,其中9#、12#作用最强,且具有时间和剂量依赖性。AO/EB荧光双染法染色及流式细胞术(PI)结果表明姜黄素衍生物9#、12#可以显著的诱导HL-60细胞凋亡,并呈剂量和时间依赖性。结论姜黄素衍生物9#、12#可能通过诱导细胞凋亡抑制细胞生长。     

姜黄素衍生物体外释放及抗肿瘤作用研究

目的 研究姜黄素衍生物mPEG_2k-Gly-Cur,mPEG_2k-Gly-Cur-OA和Cur-OA₂的体外释放情况及其体外抗肿瘤作用。方法 采用高效液相色谱法,进行姜黄素衍生物在人肝癌细胞株HepG2培养上清液中水解释放特性的研究;采用MTT法对各姜黄素衍生物体外抗肿瘤细胞活性进行初步评价。结果 建立了姜黄素的HPLC检测条件,在灭活的细胞培养上清液中,mPEG_2k-Gly-Cur和mPEG_2k-Gly-Cur-OA可以以相对合适的速度缓慢释放姜黄素,而Cur-OA₂释放非常缓慢;但在未灭活处理的细胞培养上清液中姜黄素衍生物释放速度均明显加快,表明衍生物可以通过酶促反应加速释放。体外MTT实验证实3个姜黄素衍生物具有较好的抗肿瘤作用,而且Cur-OA₂活性最强,但相对游离姜黄素均有所下降。结论 姜黄素酚羟基经衍生化后可有效提高水溶液中稳定性,而油酸双酯化衍生物可能通过肝癌细胞吞噬作用增强药效,值得进一步深入的系统研究。     

姜黄素衍生物FM0817体外抗肿瘤活性研究

目的对比研究姜黄素衍生物FM0817与姜黄素对9株体外培养肿瘤细胞的增殖抑制作用。方法应用MTT法检测黄素衍生物FM0817与姜黄素耐9株体外培养肿瘤细胞的增殖抑制率。结果黄素衍生物FM0817与姜黄素对9株肿瘤细胞Ic50平均值分别为1．95μg·mL^-1和10．84μg·mL^-1,FM0817对多种肿瘤细胞的增殖抑制作用明显强于其母核姜黄素。结论姜黄素衍生物FM0817具有较强的体外抗肿瘤活性,有进一步开发研究的前景。     

双亲姜黄素衍生物减轻大鼠肝纤维化与抗炎抗氧化作用的研究

目的探讨新型双亲姜黄素衍生物(curc-OEG)对四氯化碳(CCl4)诱导大鼠肝纤维化的抗炎抗氧化作用。方法大鼠分为正常组、模型组、姜黄素组和姜黄素衍生物组。除正常组外,其余各组给予CCl4混合液皮下注射,每周2次。造模4周后,正常组、模型组给与尾静脉注射生理盐水,姜黄素组给予姜黄素400 mg·kg-1·d-1灌胃治疗,姜黄素衍生物组给予姜黄素衍生物100 mg·kg-1·d-1尾静脉注射。治疗4周后分别取血清及肝组织标本。血清检测ALT、AST水平;肝组织做病理学检查,Real-time PCR法检测相关炎症因子的mRNA表达水平,试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)水平。结果正常组、模型组、姜黄素组和姜黄素衍生物组ALT水平分别为:(31.7±8.7)U·L-1、(383.0±75.6)U·L-1、(406.3±204.7)U·L-1、(107.0±73.7)U·L-1;AST水平分别为:(137.7±32.7)U·L-1、(585.3±36.7)U·L-1、(485.0±246.5)U·L-1、(202.7±56.0)U·L-1,姜黄素衍生物较姜黄素显示出更好的护肝降酶作用(P<0.05)。肝脏病理切片显示姜黄素衍生物较姜黄素具有更明显的延缓肝脏脂肪变性、减轻炎症细胞浸润及抗肝纤维化的作用。与姜黄素比较,姜黄素衍生物明显下调炎症相关因子NF-κB、IL-1β、IL-6、TNF-α、COX-2mRNA及蛋白表达水平(P<0.05);明显降低肝组织中MDA水平,提高GSH、SOD表达水平,增强抗氧化能力。结论姜黄素衍生物较传统姜黄素具有更好的抗炎、抗氧化作用,能够有效地延缓四氯化碳诱导的肝纤维化进程。     

姜黄素衍生物合成的研究进展

大量研究表明姜黄素具有抗肿瘤、抗炎、抗氧化、抗肝细胞毒性、抗菌等作用,在保健品及药物开发利用方面具有广泛的前景.近年来,以姜黄素为先导化合物,进行结构修饰合成其衍生物巳成为国内外研究的热点,国内外学者合成了大量的姜黄素衍生物.本文将对姜黄素衍生物合成的研究进展做简要的综述.     

姜黄素及其衍生物抗肿瘤作用的研究进展

姜黄素(curcumin)是从姜科植物姜黄(curcuma)中提取的一种具有酚基和醌基的天然药物.研究证实姜黄素具有抑制肿瘤细胞增殖,诱导细胞凋亡的作用.因其抗肿瘤谱广,毒副作用小,美国国立肿瘤研究所已将其列为第三代癌化学预防药物[1].近年来.国内外对姜黄素的研究日益增多,本文就姜黄素及其衍生物在抗肿瘤方面的研究成果...     

姜黄素衍生物FM0807体内抗炎作用研究

目的研究姜黄素衍生物FM0807的体内抗炎作用;方法通过建立二甲苯致小鼠耳廓肿胀、角叉菜胶致小鼠足跖肿胀、棉球植人法诱发慢性肉芽肿等炎症模型,探讨姜黄素衍生物FM0807的体内抗炎作用;结果姜黄素衍生物FM0807高、中、低各剂量对二甲苯致小鼠耳廓肿胀、角叉菜胶致小鼠足跖肿胀、棉球植人法诱发慢性肉芽肿均有明显的抑制作用;结论姜黄素衍生物FM0807对急、慢性炎症有明显的效果。     

姜黄素抗肿瘤作用基础与临床研究进展

姜黄素是中药姜黄根茎的主要活性成分,是一种疏水性多酚,具有广泛的生物和药理活性,可用于治疗肿瘤、糖尿病、炎症、神经退行性疾病、心血管疾病、代谢综合征和肝病等,其中姜黄素的抗肿瘤作用更是受到了广泛的关注。本文主要综述了姜黄素的抗肿瘤作用及其机制,如靶向调节肿瘤细胞周期、抑制血管生成、促进肿瘤细胞凋亡等信号通路和相关靶点,姜黄素的药物代谢和代谢产物、结构修饰及衍生物、新型药物递送系统,以及姜黄素的临床研究现状,包括姜黄素与化疗药物联合应用的基础和临床研究进展。希望通过综述姜黄素的基础和临床研究现状,以揭示其临床应用前景,也为其相关领域的进一步研究提供参考。     

Curcumin analogues and derivatives with anti-proliferative and anti-inflammatory activity: Structural characteristics and molecular targets

ABSTRACT

Introduction: Curcumin (Diferuloylmethane) is a natural phenolic compound, which belongs to the curcuminoid family, presenting pleiotropic activity and low bioavailability. A lot of recent research is focused on the design and synthesis of curcumin analogs as antiproliferative and anti-inflammatory agents improving the bioavailability and target selectivity. Their structural characteristics and functional groups seem to define the extent of the biological activity.

Areas covered: Publications (2008–2018), describing curcumin analogs and curcumin derivatives are analyzed. Structural characteristics, functional groups, modelling studies, structure activity relationships, biological evaluation in vitro/in vivo as antiproliferative and anti-inflammatory agents are included. Furthermore, a wide range of biological results derived from different targets are also summarized.

Expert opinion: Several curcumin analogs and derivatives appear to have a high biological impact as well as promising antiproliferative and anti-inflammatory activities. Their clinical evaluation will be critical to assess therapeutic utility. Compounds for which the mechanism of action is well defined can serve as lead compounds for the design of new more potent molecules.     

抗肿瘤前药-姜黄素衍生物的设计合成及初步活性测试

目的:为了提高姜黄素的抗癌活性及选择性,考虑将之做成前药形式.方法:从几种氨基酸出发,经过马来酸酐活化后与姜黄素结合,得到四个化合物.利用MTT法对四个目标化合物进行了体外抗肿瘤活性评价.结果与结论:其结构经IR,1HNMR和13CNMR确证.目标化合物对胰腺癌细胞株SW-1990和膀胱癌细胞株T24的抑制试验结果表明,四个化合物对这两种细胞的抑制作用均优于阳性对照药5-Fu.     

The increased cellular uptake and biliary excretion of curcumin by quercetin: a possible role of albumin binding interaction

Curcumin and quercetin are natural compounds with a wide spectrum of activities, including antioxidant and anticancer activities. In this study, the combined effect of the two compounds was investigated, with special emphasis on the pharmacokinetics of curcumin by the quercetin-induced changes in the albumin binding of curcumin. We evaluated the effect of quercetin on the binding of curcumin to albumin and on the uptake of curcumin into the cells of the human colon carcinoma cell line WiDr. In addition, we also investigated changes in the in vivo pharmacokinetics of curcumin and curcumin sulfate (the major metabolite of curcumin) coadministered with quercetin. We found that quercetin inhibited the binding of curcumin to albumin and increased the uptake of curcumin into WiDr cells, the human colon carcinoma cell. The quercetin-induced increased uptake (1.6-fold) of curcumin into WiDr cells was also confirmed by an ex vivo study. The in vivo pharmacokinetics of curcumin showed obvious changes when it was coadministered with quercetin, with the significantly lower plasma concentration and greater biliary excretion of curcumin and curcumin sulfate. The present study suggests that quercetin could enhance the cellular uptake of curcumin and modulate in vivo pharmacokinetics of curcumin, and it could be related to albumin-binding interaction.     

Synthetic derivatives of curcumin and their activity against Leishmania amazonensis

In a previous work, the in vitro and in vivo activity of a series of diarylheptanoid derivatives against Leishmania amazonensis has been described. Based on the promising results, ten new compounds belonging to the same chemical class were synthesized and have been investigated in relation to their leishmanicidal activity. The compounds were obtained through several chemical modifications on the basic structure of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in an attempt to increase its effectiveness and decrease the potential toxic effects. The drugs were assayed in vitro against L. amazonensis promastigotes and using pentamidine isethionate as reference drug. The results showed that the most effective compound is 1,7-bis-(4-propargyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, which is about ten times more efficient than the original curcumin. Nevertheless, these results did not allow us to make any correlation between the leishmanicidal activity and the chemical structure of the compounds.     

姜黄素抗肿瘤机制及其应用的研究进展

目的为姜黄素的进一步研究提供参考,为其在抗肿瘤方面的应用提供科学依据。方法在中国知网和PubMed 2个数据库中检索有关姜黄素抗肿瘤及其应用的相关研究文献,并进行综述。结果姜黄素的抗肿瘤机制主要集中在诱导细胞凋亡并抑制细胞增殖和生长及抑制肿瘤细胞的侵袭和抗炎等。姜黄素的相关应用和研究主要有姜黄素脂质体的制备和应用,姜黄素在声光动力抗肿瘤方面的应用研究,姜黄素逆转癌细胞的多药耐药性及姜黄素联合化疗药物抗肿瘤的相关研究。结论姜黄素抗肿瘤机制集中于多个靶点,针对这些作用机制的研究远远不足,后续应加强有关姜黄素临床抗肿瘤方面的相关研究。     

Overcoming multidrug resistance in human cancer cells by natural compounds

Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. P-glycoprotein belongs to the large ATP-binding cassette (ABC) transporter superfamily of membrane transport proteins. P-glycoprotein mediates resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel, by actively extruding the drugs from the cells. The quest for inhibitors of anticancer drug efflux transporters has uncovered natural compounds, including (-)-epigallocatechin gallate, curcumin, capsaicin, and guggulsterone, as promising candidates. In this review, studies on the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized.     

Inhibitory effect of curcumin analogs on tissue factor procoagulant activity and their preliminary structure–activity relationships

With the aim to explore the multifunctional behaviors of curcumin analogs and to discover new small molecular tissue factor inhibitors, twelve mono carbonyl curcumin analogs of three classes were synthesized and their effect on tissue factor procoagulant activity was evaluated in the human monoblastic leukemia THP-1 cells stimulated by LPS. The most potent compounds 2a exhibited the dramatically enhanced activity with the IC₅₀ values of 0.053 nM. Their preliminary structure–activity relationship was also discussed.     

姜黄素单羰基类似物的研究进展

目的总结近几年来姜黄素单羰基类似物在合成、稳定性及药理活性方面的研究进展。方法通过检索查找相关文献。结果合成的姜黄素单羰基类似物不仅稳定性有所提高,且其药理活性也有所提高。结论姜黄素单羰基类似物具有进一步的研究价值和良好的应用前景。     

Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment

As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin. Moreover, curcumin was reported to act in synergism with several natural compounds or synthetic agents commonly used in chemotherapy. Based on this, curcumin could thus be considered as a good candidate for cancer prevention and treatment when used alone or in combination with other conventional treatments.