A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.     

基于TopomerCoMFA方法的姜黄素类化合物的三维定量构效关系研究

易位体比较分子场（TopomerCoMFA）是一种快速、基于片段分析、可以用于预测官能团、优化生物活性或结构的3D-QSAR方法。采用TopomerCoMFA对20个姜黄素及其类似物进行三维定量构效关系研究,建立有效的TopomerCoMFA模型,其交叉验证相关系数q2=0.593,非交叉相关系数r2=0.995,表明该模型合理、可信,并具有良好的预测能力。     

HPLC法测定姜黄中姜黄素类化合物的含量

采用高效液相色谱法测定姜黄中主要姜黄素类化合物,色谱柱为C18,流动相为乙腈和0.5%冰醋酸,采样梯度洗脱,检测波长为425 nm。结果表明,姜黄样品中姜黄素类化合物的加样回收率分别为99.87%,99.91%,99.51%,RSD分别为0.75%,1.217%,1.06%。本方法对测定姜黄中主要的姜黄素类化合物快速简单,重复性好,为植物提取行业的含量测定提供依据。     

姜黄素的抗氧化机制及以其为先导物的抗氧化化合物研究进展

姜黄素具有抗氧化、抗肿瘤、抑菌等多种药理活性。近年来为开发姜黄素类抗氧化剂,国内外研究者设计和合成了大量姜黄素衍生物。本文介绍了姜黄素及其衍生物的抗氧化机制,重点概述基于抗氧化的姜黄素抗氧化衍生物的研究进展。     

Design,Synthesis and Evaluation of Novel Derivatives of Curcuminoids with Cytotoxicity

Curcumin and curcuminoids have been discussed frequently due to their promising functional groups (such as scaffolds of α,β-unsaturated β-diketone, α,β-unsaturated ketone and β′-hydroxy-α,β-unsaturated ketone connected with aromatic rings on both sides) that play an important role in various bioactivities, including antioxidant, anti-inflammatory, anti-proliferation and anticancer activity. A series of novel curcuminoid derivatives (a total of 55 new compounds) and three reference compounds were synthesized with good yields using three-step organic synthesis. The anti-proliferative activities of curcumin derivatives were examined for six human cancer cell lines: HeLaS3, KBvin, MCF-7, HepG2, NCI-H460 and NCI-H460/MX20. Compared to the IC₅₀ values of all the synthesized derivatives, most α,β-unsaturated ketones displayed potent anti-proliferative effects against all six human cancer cell lines, whereas β′-hydroxy-α,β-unsaturated ketones and α,β-unsaturated β-diketones presented moderate anti-proliferative effects. Two potent curcuminoid derivatives were found among all the novel derivatives and reference compounds: (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a). These were selected for further analysis after the evaluation of their anti-proliferative effects against all human cancer cell lines. The results of apoptosis assays revealed that the number of dead cells was increased in early apoptosis and late apoptosis, while cell proliferation was also decreased after applying various concentrations of (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) to MCF-7 and HpeG2 cancer cells. Analysis of the gene expression arrays showed that three genes (GADD45B, SESN2 and BBC3) were correlated with the p53 pathway. From the quantitative PCR analysis, it was seen that (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) effectively induced the up-regulated expression of GADD45B, leading to the suppression of MCF-7 cancer cell formation and cell death. Molecular docking analysis was used to predict and sketch the interactions of the GADD45B-α,β-unsaturated ketone complex for help in drug design.     

Effects of Quercetin and Curcumin Combination on Antibacterial,Antioxidant, In Vitro Wound Healing and Migration of Human Dermal Fibroblast Cells

Wound healing impairment due to a postponed, incomplete, or uncoordinated healing process has been a challenging clinical problem. Much research has focused on wound care, particularly on discovery of new therapeutic approaches for acute and chronic wounds. This study aims to evaluate the effect of the combination of quercetin and curcuminoids at three different ratios on the antimicrobial, antioxidant, cell migration and wound healing properties. The antioxidant activities of quercetin, curcuminoids and the mixtures were tested by DPPH and ABTS free radical scavenging assays. The disc diffusion method was performed to determine the antibacterial activities of quercetin, curcuminoids and the mixtures against S. aureus and P. aeruginosa. The cytotoxicity and cell migratory enhancing effects of quercetin, curcuminoids and the mixtures against human dermal fibroblasts were investigated by MTT assay, scratch assay and Transwell migration assay, respectively. The results showed the synergism of the quercetin and curcuminoid combination to inhibit the growth of S. aureus and P. aeruginosa, with the inhibition zone ranging from 7.06 ± 0.25 to 8.78 ± 0.38 mm, respectively. The DPPH free radical scavenging assay demonstrated that the combination of quercetin and curcuminoids yielded lower IC₅₀ values (15.38–23.70 µg/mL) than curcuminoids alone (25.75 µg/mL). Quercetin and a 3:1 quercetin/curcuminoid mixture at non-toxic concentrations showed the ability to stimulate the migration of fibroblasts across the matrix, whereas only quercetin alone accelerated the wound closure of fibroblasts. In conclusion, the mixture of quercetin and curcuminoids at a 3:1 ratio was the best formulations for use in wound healing due to the antimicrobial, antioxidant and cell-migration-enhancing activities.     

高效液相色谱法检测果冻中的姜黄素类化合物

目的建立果冻制品中姜黄素类化合物的高效液相色谱测定方法。方法样品用甲醇水混合溶液(7+3,V:V)提取,经过0.45μm微孔滤膜过滤后进样分析。色谱柱:Kinetex PFP五氟苯基柱;流动相:0.1%甲酸水和0.1%甲酸乙腈;洗脱方式:等度;检测器波长420 nm;流速为1 mL/min;柱温:室温;进样量为4.0μL;采用色谱峰保留时间定性,外标法峰面积定量。结果标准溶液在1μg/m L~100μg/m L范围内线性良好,相关系数0.999,平均回收率在93.0%~103.2%之间,相对标准偏差2.73%~4.89%。结论该方法具有样品预处理简单等特点,实测中发现可吸果冻和凝胶果冻中普遍含有姜黄素成分,姜黄素类化合物总含量在1~15 mg/kg之间。     

姜黄素类化合物及姜黄素衍生物对酪氨酸酶抑制作用的研究

从中药姜黄的提取物中分离了姜黄素、单去甲氧基姜黄素及双去甲氧基姜黄素,并对姜黄素进行了引入羧酸基团、乙酰化、氢化等结构修饰,合成了4个姜黄素衍生物,并测试了这些化合物对酪氨酸酶的抑制活性。结果表明,天然姜黄素类化合物中单去甲氧基姜黄素的活性最强,IC50为0.076 mmol/L;姜黄素的结构修饰化合物中,带羧基的姜黄素衍生物表现出很强的抑制活性,IC50为0.056 mmol/L。抑制动力学研究表明,单去甲氧基姜黄素及带羧基的姜黄素衍生物对酪氨酸酶的抑制均属于非竞争性抑制类型。     

Simple HPLC Method for Resolution of Curcuminoids with Antioxidant Potential

ABSTRACT:  Development of methodology for qualitative analysis and quantitative separation of individual curcuminoids in curcumin removed turmeric oleoresin (CRTO) and study of antioxidant activity of individual curcuminoids have been achieved in the present study. A simple HPLC protocol was outlined for optimal resolution of curcuminoids (I), (II), and (III) on an Exil-NH₂ column using isocratic elution with a mixture of isopropanol and water. CRTO is shown to be good source for the compounds II and III, as they are in an enriched form. The optimum resolution of the curcumin and its analogs in the present method developed, affords a facile method for estimation of individual curcuminoids in turmeric samples, which is an improvement over the standard AOAC method which estimates only total curcuminoids. The free radical scavenging capacity of pure curcuminoids I, II, and III, as determined by DPPH method at 100 ppm concentration was 88%, 80%, and 68% with IC₅₀ values being 56, 62, and 73 ppm, respectively. Their antioxidant potential could render them useful as important nutraceuticals or functional food ingredients.