Development and validation of UPLC method for quality control of Curcuma longa Linn.: Fast simultaneous quantitation of three curcuminoids

A new reversed phase ultra performance liquid chromatography (UPLC) method was developed for the rapid quantification of three curcuminoids (curcumin (C), desmethoxycurcumin (DMC) and bisdesmethoxycurcumin (BDMC)) in Curcuma longa Linn. (C. longa) using a Waters BEH Shield RP C₁₈, 2.1 mm × 100 mm, 1.7 μm column. The runtime was 2 min. The influence of column temperature and mobile phase on resolution was investigated. The method was validated according to the ICH guideline for validation of analytical procedures with respect to precision, accuracy, and linearity. The limits of detection were 40.66, 49.38 and 29.28 pg for C, DMC and BDMC, respectively. Limits of quantitation for C, DMC and BDMC, were 134.18, 164.44 and 97.50 pg, respectively. Linear range was from 3.28 to 46.08 μg/ml. The mean ± SD percent recoveries of curcuminoids were 99.47 ± 1.66, 99.50 ± 1.99 and 97.77 ± 2.37 of C, DMC and BDMC, respectively. Comparison of system performance with conventional HPLC was made with respect to analysis time, efficiency and sensitivity. The proposed method was found to be reproducible and convenient for quantitative analysis of three curcuminoids in C. longa. This work provided some references for quality control of C. longa.     

The inhibitory effects of different curcuminoids on β-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells

The hallmark of Alzheimer's disease (AD) is the accumulation of β-amyloid protein (Aβ). Aβ is generated from the β-amyloid precursor protein (APP) through the proteolysis of β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. Aβ₄₂ isoform is more easily aggregate and more toxic to neurons than any other Aβ isoforms, thus being regarded as the primary toxic specie in AD. Curcumin mix has potent anti-amyloidogenic effect and shows great promise for AD treatment and prevention. The present study was conducted to examine the effects of curcumin mix and its different curcuminoids including curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) on Aβ₄₂, APP and BACE1. We found that Cur was the most active curcuminoid fraction in suppressing Aβ₄₂ production and the order of inhibitory potency of other curcuminoids was DMC > curcumin mix > BDMC. Cur, but not other curcuminoids, could reduce APP protein expression and none of curcuminoids affected APP mRNA level. BDMC could reduce BACE1 mRNA and protein levels, while DMC only affected BACE1 mRNA expression. Our data indicate that the anti-amyloidogenic effect of Cur may be mediated through the modulation of APP, while the anti-amyloidogenic effect of BDMC may be mediated through the modulation of BACE1.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Self-emulsifying drug delivery system improves preventive effect of curcuminoids on chronic heart failure in rats

Several studies have reported the preventive or therapeutic effect of curcuminoids on chronic heart failure (CHF), but their application was limited due to low solubility and bioavailability. Our previous study indicates that self-emulsifying drug delivery system (SEDDS) improves the solubility and bioavailability of curcuminoids. Thus, the aim of this work was to investigate whether SEDDS could improve preventive effect of curcuminoids on CHF in rats. CHF model was were established by coronary artery ligation. Ninety rats were randomly and averagely divided into sham, model, low- or high-dose suspension or SEDDS of curcuminoids (66.68 or 266.68?mg/kg) groups. Hemodynamic indices were recorded by multipurpose polygraph. Serum oxidative indices, B-type natriuretic peptide (BNP) and heart weight index were determined by kits and electronic balance. Myocardial infarct area, ventricular dilatation degree and collagen volume fraction of myocardial interstitium were analyzed by Masson staining, picric acid and sirius red staining, light microscopy and image analysis system. Myocardial histopathology was observed by hematoxylin and eosin staining, Masson staining and light microscopy. Reduction of ventricular pump function, increase of BNP level and heart weight index, myocardial lipid peroxidation damage, myocardial infarction, myocardial fibrosis, and cardiac enlargement were detected or observed in model group relative to those in sham group. After treatment with suspension or SEDDS of curcuminoids, the above-mentioned pathological changes were obviously reversed relative to those in model group. Meanwhile, the ameliorative effect of SEDDS of curcuminoids was markedly better than that of suspension of curcuminoids. This work provides a valuable reference from pharmacodynamics for development of curcuminoids pharmaceutics.     

姜黄素类化合物提高线虫的抗氧化应激能力

 目的：研究姜黄素类化合物姜黄素（Cur）、去甲氧基姜黄素（DMC）和双去氧基姜黄素（BDMC）在秀丽隐杆线虫体内的抗氧化应激作用并探讨其作用机制。方法：应用胡桃醌诱导,观察姜黄素类化合物对线虫在氧化应激状态下生存率的影响;用分子探针2,7-二氯二氢荧光素二乙酸酯（H 2DCF-DA）观察姜黄素类化合物对线虫氧化应激状态下体内活性氧（ROS）的影响;应用荧光显微镜及图像软件分析姜黄素类化合物对线虫氧化应激相关蛋白谷胱甘肽S-转移酶4(GST-4)表达的影响。结果：经姜黄素类化合物预处理后,氧化应激条件下线虫的生存率明显提高;姜黄素类化合物显著抑制了氧化应激状态下线虫体内的ROS水平;在氧化应激条件下,Cur处理组及DMC处理组线虫的GST-4表达量均显著增高（P<0.05）。结论：姜黄素类化合物可能通过降低线虫体内的ROS水平、上调特定应激蛋白GST-4的表达而增强其抗氧化应激能力。     

姜黄素类化合物的研究进展

姜黄素作为中药姜黄的主要活性成分,对炎症、肿瘤、代谢类疾病和神经系统疾病均显示良好的应用前景,因其生物利用度低限制了临床应用。围绕姜黄素的结构修饰一直是药物学家的兴趣所在。本文就近五年姜黄素类化合物研究进展进行综述,为开发姜黄素类药物提供参考。     

Effect of Some Natural Products Either Alone or in Combination on Gastritis Induced in Experimental Rats

Gastritis, an inflammatory state in gastric mucosa, can be induced experimentally in various ways. The present study considered the iodoacetamide model (Iodo). Omega-3 fatty acids (fish oil), black seed oil, and curcuminoids (natural products) in addition to omeprazole (synthetic proton-pump inhibitor) were tested. Supplementation of 0.1% iodoacetamide to drinking water of experimental rats for two consecutive weeks resulted in: (i) increased serum nitric oxide (NO) and gastrin, and decreased pepsinogen, (ii) depletion of gastric mucosal glutathione (GSH), and (iii) increased gastric mucosal lipid peroxidation (MDA), but failed to affect gastric mucosal myeloperoxidase (MPO) activity. Histological examination showed marked neutrophilic infiltration after 1 week of iodoacetamide administration and shedding of apical cell layer with pale edematous vacuolated gastric gland cells and thickening of muscularis mucosa after 2 weeks of iodoacetamide intake. Individual administration of omega-3 fatty acids 12 mg/kg, black seed oil 50 mg/kg, and curcuminoids 50 mg/kg body weight orally daily for 3 weeks decreased MDA, gastrin, and NO, and normalized mucosal GSH but failed to affect serum pepsinogen level. Combined administration of these natural products for 3 weeks normalized MPO activity, and other effects were nearly the same as with individual use. Omeprazole administration 30 mg/kg body weight orally daily for 3 weeks induced a similar response except for an observed increase in serum gastrin and pepsinogen levels.