Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.     

Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice

Curcumin has been shown to have anti malarial activity, but poor bioavailability and chemical instability has hindered its development as a drug. We have bound curcumin to chitosan nanoparticles to improve its bioavailability and chemical stability. We found that curcumin bound to chitosan nanoparticles did not degrade that rapidly in comparison to free curcumin when such particles were incubated in mouse plasma in vitro at room temperature. The uptake of bound curcumin from chitosan nanoparticles by mouse RBC was much better than from free curcumin. Oral delivery of curcumin bound chitosan nanoparticles to normal mice showed that they can cross the mucosal barrier intact and confocal microscopy detected the nanoparticles in the blood. Curcumin loaded chitosan nanoparticles when delivered orally improved the bioavailability of curcumin in the plasma and RBC. While mice infected with a lethal strain of Plasmodium yoelii (N-67) died between 8 and 9 days post infection, feeding of chitosan nanoparticles alone made them to survive for five more days. Feeding 1mg of native curcumin to infected mice per day for seven days resulted in survival of one third of mice but under the same condition when 1mg of curcumin bound to chitosan nanoparticles was fed all the mice survived. Like chloroquine, curcumin inhibited parasite lysate induced heme polymerization in vitro in a dose dependent manner and curcumin had a lower IC(50) value than chloroquine. We believe that binding of curcumin to chitosan nanoparticles increases its chemical stability and enhances its bioavailability when fed to mice. In vitro data suggest that it can inhibit hemozoin synthesis which is lethal for the parasite.     

Plasmodium chabaudi: efficacy of artemisinin + curcumin combination treatment on a clone selected for artemisinin resistance in mice

Recent studies have proposed curcumin as a potential partner for artemisinin in artemisinin combination therapies to treat malaria infections. The efficacy of curcumin alone and in combination with artemisinin was evaluated on a clone of Plasmodium chabaudi selected for artemisinin resistance in vivo. The addition of piperine as an enhancer of curcumin activity was also tested.Results indicated that curcumin, both alone and in combination with piperine had only a modest antimalarial effect and was not able to reverse the artemisinin-resistant phenotype or significantly affect growth of the tested clone when used in combination with artemisinin. This is in contrast with previous in vivo work and calls for further experimental evaluation of the antimalarial potential of curcumin.     

Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules

Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC₅₀ of curcumin was found to be 5 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.     

Synthesis,antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin

A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines. Six of the analogues showed potent cytotoxicity towards these cell lines with IC₅₀ values below 1 μM, which is better than doxorubicin, a US FDA approved drug. Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening. This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.     

姜黄素对小鼠胆汁淤积性肝纤维化的改善作用及其机制研究*

目的:探讨姜黄素对小鼠胆管结扎所致的胆汁淤积性肝纤维化的保护作用,为肝纤维化治疗提供新的治疗方法。方法:42只健康成年雄性BALB/c小鼠随机分为假手术(n=6)处理组、假手术+姜黄素(n=6)处理组、胆管结扎(BDL)处理组(n=10)、BDL+姜黄素处理组(n=10),BDL+姜黄素+锌原卟啉(ZnPP)处理组(n=10)。BDL手术7 d后,假手术+姜黄素组、BDL+姜黄素组每日给予姜黄素(30 mg / kg)腹腔注射;BDL+姜黄素+ZnPP组每日给予姜黄素(30 mg / kg)以及nPP(50 μmol/ kg)腹腔注射;对于假手术组和BDL组,小鼠每天一次腹膜内注射等体积的盐水。整个给药过程持续7 d。小鼠BDL14 d后,取血和肝脏组织,检测谷草转氨酶(AST)、谷丙转氨酶(ALT)水平,观察肝组织病理形态变化、肝纤维化情况、检测肝组织中血红素加氧酶-1(HO-1)的蛋白表达。结果:与假手术组相比,BDL组小鼠肝脏胆囊肿大,血清谷草转氨酶(ALT)、谷丙转氨酶(AST)水平显著升高 (P＜0.05),同时,天狼星红染色及促纤维化相关基因的qRT-PCR结果显示肝脏出现胶原蛋白沉积,巨噬细胞及中性粒细胞免疫组化结果显示肝脏出现炎性细胞浸润;与BDL组相比,姜黄素治疗组血清ALT、AST水平明显降低(P＜0.05),胶原蛋白沉积及炎性细胞浸润情况有所改善,同时,补充姜黄素后HO-1表达升高(P＜0.05);对姜黄素治疗组给予HO-1活性抑制剂ZnPP发现,姜黄素对肝损伤的保护作用被逆转。结论:姜黄素可以改善BDL所致的肝脏炎症及肝纤维化,这种保护作用可能与姜黄素调节HO-1活性有关。     

Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking,molecular dynamics,and charge density analysis

Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer’s disease, as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution, and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE. Further, the charge density distribution and the electrostatic properties of curcumin molecule (lifted from the active site of rhAChE) were determined from the high level density functional theory (DFT) calculations coupled with the charge density analysis. On the other hand, the curcumin molecule was optimized (gas phase) using DFT method and further, the structure and charge density analysis were also carried out. On comparing the conformation, charge density distribution and the electrostatic potential of the active site form of curcumin with the corresponding gas phase form reveals that the above said properties are significantly altered when curcumin is present in the active site of rhAChE. The conformational stability and the interaction of curcumin in the active site are also studied using molecular dynamics simulation, which shows a large variation in the conformational geometry of curcumin as well as the intermolecular interactions.     

Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin

To understand the relative importance of phenolic O-H and the CH-H hydrogen on the antioxidant activity and the free radical reactions of Curcumin, (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), biochemical, physicochemical, and density functional theory (DFT) studies were carried out with curcumin and dimethoxy curcumin (1,7-bis[3, 4-dimethoxy phenyl]-1,6-heptadiene-3,5-dione). The antioxidant activity of these compounds was tested by following radiation-induced lipid peroxidation in rat liver microsomes, and the results suggested that at equal concentration, the efficiency to inhibit lipid peroxidation is changed from 82% with curcumin to 24% with dimethoxy curcumin. Kinetics of reaction of (2,2'-diphenyl-1-picrylhydrazyl) DPPH, a stable hydrogen abstracting free radical was tested with these two compounds using stopped-flow spectrometer and steady state spectrophotometer. The bimolecular rate constant for curcumin was found to be approximately 1800 times greater than that for the dimethoxy derivative. Cyclic voltammetry studies of these two systems indicated two closely lying oxidation peaks at 0.84 and 1.0 V vs. SCE for curcumin, while only one peak at 1.0 V vs. SCE was observed for dimethoxy curcumin. Pulse radiolysis induced one-electron oxidation of curcumin and dimethoxy curcumin was studied at neutral pH using (*)N(3) radicals. This reaction with curcumin produced phenoxyl radicals absorbing at 500 nm, while in the case of dimethoxy curcumin a very weak signal in the UV region was observed. These results suggest that, although the energetics to remove hydrogen from both phenolic OH and the CH(2) group of the beta-diketo structure are very close, the phenolic OH is essential for both antioxidant activity and free radical kinetics. This is further confirmed by DFT calculations where it is shown that the -OH hydrogen is more labile for abstraction compared to the -CH(2) hydrogen in curcumin. Based on various experimental and theoretical results it is definitely concluded that the phenolic OH plays a major role in the activity of curcumin.     

Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels

Curcumin (diferuloylmethane) is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Experimental studies with diabetic animals demonstrate that curcumin supplementation can suppress cataract development and collagen cross-linking, promote wound healing, and lower blood lipids and glucose levels. The mechanism by which curcumin may cause diabetes-associated vascular damage to regress is not known. Erythrocytes were treated with high levels of glucose (mimicking diabetes) in the presence or absence of curcumin (0-10 muM) in the medium at 37 degrees C for 24 h. This study demonstrates that curcumin prevents protein glycosylation and lipid peroxidation caused by high glucose levels using an erythrocyte cell model. This study also suggests that curcumin may inhibit oxygen radical production caused by high glucose concentrations in a cell-free system, and increase glucose utilization in erythrocytes. This provides evidence for a novel mechanism by which curcumin supplementation may prevent the cellular dysfunction associated with diabetes.     

姜黄素对双酚A致小鼠卵巢氧化损伤的保护

本文旨在研究姜黄素(CRC)对双酚A(BPA)诱导的小鼠卵巢氧化损伤的保护作用。将28日龄雌性小鼠分为对照组、姜黄素组、双酚A组和双酚A加姜黄素组,连续灌胃6周。收集卵巢,通过活性氧(ROS)水平的检测、卵巢闭锁卵泡的观察以及3种关键抗氧化酶表达和活性的测定,研究姜黄素对双酚A诱发的卵巢氧化损伤的保护作用及机制。结果显示,与对照组相比,双酚A暴露后明显增加了卵巢的活性氧水平,造成氧化应激,提高了卵巢中有腔卵泡闭锁比例。与双酚A组相比,双酚A和姜黄素共同处理组降低了卵巢的活性氧水平和卵巢中有腔卵泡闭锁比例。双酚A暴露降低了卵巢超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)以及过氧化氢酶(CAT)的表达和活性,姜黄素逆转了双酚A诱导的3种抗氧化酶表达和活性的下降。结果表明,姜黄素可逆转双酚A通过氧化应激造成的卵巢损伤。     

姜黄色素增溶的研究

本研究以脂溶性姜黄色素为材料,探讨其增溶后的水溶性、耐光性、耐加热性、安全性及增溶费用.结果表明,增溶后的姜黄色素不仅水溶性好,而且色泽鲜艳、着色力强,耐光性、耐加热性也较好;增溶后的姜黄色素安全无毒;增溶费用低.从而为工业化生产水溶性姜黄色素提供了理论依据.     

Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation

Liposomal formulation of curcumin is an important therapeutic agent for the treatment of various cancers. Despite extensive studies on the biological effects of this formulation in cancer treatment, much remains unknown about curcumin–liposome interactions. Understanding how different lipid bilayers respond to curcumin molecule may help us to design more effective liposomal curcumin. Here, we used molecular dynamics simulation method to investigate the behavior of curcumin in two lipid bilayers commonly used in preparation of liposomal curcumin, namely dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylglycerol (DMPG). First, the free energy barriers for translocation of one curcumin molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). The computed free energy profile exhibits a global minimum at the solvent–headgroup interface (LH region) for both lipid membranes. We also evaluated the free energy difference between the equilibrium position of curcumin in the lipid bilayer and bulk water as the excess chemical potential. Our results show that curcumin has the higher affinity in DMPG compared to DPPC lipid bilayer (?8.39 vs. ?1.69 k_BT) and this is related to more hydrogen bond possibility for curcumin in DMPG lipid membrane. Next, using an unconstrained molecular dynamic simulation with curcumin initially positioned at the center of lipid bilayer, we studied various properties of each lipid bilayer system in the presence of curcumin molecule that was in full agreement with PMF and experimental data. The results of these simulation studies suggest that membrane composition could have a large effect on interaction of curcumin–lipid bilayer.     

Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation

Limited recovery of islets post-cryopreservation influences graft survival and transplantation efficiency during diabetes treatment. As curcumin, a potent antioxidant/radical scavenging compound, protects islets against beta cell toxins, we hypothesized that inclusion of curcumin during cryopreservation or during post-thaw culture or both may rescue islets from cryoinjury. To test the effect of curcumin inclusion on islet recovery murine islets were isolated by the collagenase digestion, cultured for 48 h, cryopreserved using dimethylsulphoxide as cryoprotectant -- with or without curcumin (10 microM) -- and then slow cooled to -40 degrees C before immersing them in liquid nitrogen for 7 days. Following rapid thawing with sucrose gradient and 24 h post-thaw culture -- in presence or absence of curcumin (10 microM) -- islet viability and functionality were determined. Islet recovery in curcumin treated groups was significantly higher than in groups where islets were cryopreserved without curcumin. Islets cryopreserved with curcumin also showed more intact islets as well as better morphology as compared to islets cryopreserved without curcumin. Curcumin treated islets also showed significant inhibition of ROS generation as compared to islets cryopreserved without curcumin. Glucose responsiveness and insulin secretion in islets cryopreserved with curcumin was equal to that of the freshly isolated islets as against islets cryopreserved without curcumin. Elevated level of Hsp 70 and HO-1 were observed in islets cryopreserved with curcumin and may contribute to curcumin-induced islet rescue. Hence, we conclude that inclusion of curcumin into cryopreservation medium inhibits ROS generation and corresponding islet damage and dysfunction.     

Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo

Alzheimer's disease (AD) involves amyloid beta (Abeta) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Abeta binding, we investigated whether its efficacy in AD models could be explained by effects on Abeta aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC(50) = 0.8 microM) as well as disaggregated fibrillar Abeta40 (IC(50) = 1 microM), indicating favorable stoichiometry for inhibition. Curcumin was a better Abeta40 aggregation inhibitor than ibuprofen and naproxen, and prevented Abeta42 oligomer formation and toxicity between 0.1 and 1.0 microM. Under EM, curcumin decreased dose dependently Abeta fibril formation beginning with 0.125 microM. The effects of curcumin did not depend on Abeta sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small beta-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD.     

Anticoagulant activities of curcumin and its derivative

Curcumin, a polyphenol responsible for the yellow color of the curry spice turmeric, possesses antiinflammatory, antiproliferative and antiangiogenic activities. However, anticoagulant activities of curcumin have not been studied. Here, the anticoagulant properties of curcumin and its derivative (bisdemethoxycurcumin, BDMC) were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed that curcumin and BDMC prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They inhibited the generation of thrombin or FXa. In accordance with these anticoagulant activities, curcumin and BDMC showed anticoagulant effect in vivo. Surprisingly, these anticoagulant effects of curcumin were better than those of BDMC indicating that methoxy group in curcumin positively regulated anticoagulant function of curcumin. Therefore, these results suggest that curcumin and BDMC possess antithrombotic activities and daily consumption of the curry spice turmeric might help maintain anticoagulant status.     

Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study

Curcumin, a lipid soluble antioxidant, exhibits solvent and medium sensitive absorption and fluorescence properties. Using such changes, the average binding constants of curcumin to phosphatidylcholine (PC) liposomes and human serum albumin (HSA) were estimated to be 2.5 x 10(4) M(-1) and 6.1 x 10(4) M(-1) respectively. From the studies on temperature dependent fluorescence anisotropy of liposomal curcumin and its fluorescence quenching by acrylamide and iodide, it was concluded that curcumin is located in the gel phase of the liposomes. Similarly from the studies on quenching of tryptophan fluorescence in HSA by curcumin, it was found to be in the same domain as that of tryptophan. Both liposomal and HSA vehicles were examined for the transfer of curcumin to spleen lymphocyte cells, EL4 lymphoma cell line and compared with aqueous DMSO vehicles. From these studies it was found that liposomal vehicle is capable of loading more curcumin in to cells than HSA or aqueous-DMSO, and lymphoma cells show preferential uptake of curcumin to lymphocytes. The fluorescence of curcumin in EL4 lymphoma cells was found to be significantly higher as compared to the lymphocytes. The present study demonstrates a simple and quantitative method of estimation of curcumin delivered to cells by different vehicles using absorption and fluorescence spectroscopy.     

Anti-oxidant activities of curcumin and related enones

The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), obtained from the spice turmeric, exhibits numerous biological activities including anti-cancer, anti-inflammatory, and anti-angiogenesis activities. Some of these biological activities may derive from its anti-oxidant properties. There are conflicting reports concerning the structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is a symmetrical diphenolic dienone. A series of enone analogues of curcumin were synthesized that included: (1) curcumin analogues that retained the 7-carbon spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and (3) curcumin analogues with a 3-carbon spacer (chalcones). These series included members that retained or were devoid of phenolic groups. Anti-oxidant activities were determined by the TRAP assay and the FRAP assay. Most of the analogues with anti-oxidant activity retained the phenolic ring substituents similar to curcumin. However, a number of analogues devoid of phenolic substituents were also active; these non-phenolic analogues are capable of forming stable tertiary carbon-centered radicals.     

Protective<Emphasis Type="Italic">in vivo</Emphasis> effect of curcumin on copper genotoxicity evaluated by comet and micronucleus assays

Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not genotoxic in vivo, but in vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test if in vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE) was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed to curcumin. In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by copper in the presence of curcumin.     

Retracted: Curcumin ameliorates atherosclerosis through upregulation of miR-126

The potential usage of curcumin in diverse human diseases has been widely studied, including arteriosclerosis (AS). This study focused on investigating the relationship between curcumin and AS-associated microRNA, which may provide a better understanding of curcumin in a different mechanism. Human microvascular endothelial HMEC-1 cells were treated by curcumin alone or oxidized low-density lipoprotein (ox-LDL) plus curcumin, after which the following parameters were analyzed: cell viability, migration, and the expression of AS-associated factors. The regulatory effects of curcumin on miR-126 and signaling pathways involved in AS were then studied. Further, an animal model of AS was stimulated by feeding rabbits with 1% cholesterol diet. The effects of curcumin on the animal model were explored. We found that curcumin treatment significantly reduced HMEC-1 cells viability, migration, and the protein levels of MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) in the presence or absence of ox-LDL. Meanwhile, the expression of VEGFR1 and VEGFR2 was repressed by curcumin. miR-126 was upregulated by curcumin. The abovementioned effects of curcumin on HMEC-1 cells were all attenuated when miR-126 was silenced. And also, VEGF was a target gene of miR-126, and curcumin could inhibit the activation of PI3K/AKT JAK2/STAT5 signaling pathways via miR-126. The effects of curcumin and its regulation on miR-126 and VEGF were confirmed in the animal model of AS. To sum up, curcumin exerted potent anti-AS property possibly via upregulating miR-126 and thereby inhibiting PI3K/AKT and JAK2/STAT5 signaling pathways.