PLoS One
·
2019
·Vol. 14
·期 5
·e0216711
·
IF 2.776
Xinyu Lin,Dingping Bai,Zixi Wei,Ying Zhang,Yifan Huang,Hui Deng,Xiaohong Huang
Large-scale breeding environments often lead to oxidative stress. Macrophages play an important role in the immune system and are vulnerable to reactive oxygen species (ROS), which result in macrophage death. Curcumin is the main active component of turmeric and exerts antioxidant effects. Here, we measured the activity of some antioxidant enzymes and chose the Nrf2-Keap1 signaling pathway to study the protective effects of curcumin on macrophages under oxidative stress in vitro. We used RAW264.7 cells as a research model, and oxidative damage was induced by hydrogen peroxide (H 2 O 2 ). Cell viability was measured by an MTT assay. Flow cytometry was used to measure cellular ROS and apoptosis. The effect of curcumin on Nrf2-Keap1 signaling pathway-related genes was analyzed by qRT-PCR. Furthermore, the translocation of Nrf2 protein was also investigated by Western blot analysis of total and nuclear proteins. All curcumin-treated groups exhibited increased activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Low- and middle-dose curcumin decreased malondialdehyde (MDA) and ROS levels, but high-dose curcumin increased MDA and ROS production. We found that low-dose curcumin protected cells from apoptosis, while apoptosis in the middle- and high-dose curcumin-treated groups were stagnant in the early stage. Furthermore, middle-dose curcumin upregulated Nrf2 expression after H 2 O 2 treatment for 4 h. Low- and middle-dose curcumin could activate Nrf2 and promote it to migrate into nuclei. The translocation of Nrf2 to the nucleus to upregulate the expression of haemoxygenase-1 (HO-1) was promoted in the low- and middle-dose curcumin-treated groups. The middle-dose curcumin-treated group also exhibited enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), but inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). Curcumin resisted oxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway, which could potentially promote cell survival.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 13
·2483
·
IF 3.06
Krishan Parashar,Siddhartha Sood,Ali Mehaidli,Colin Curran,Caleb Vegh,Christopher Nguyen,Christopher Pignanelli,Jianzhang Wu,Guang Liang,Yi Wang,Siyaram Pandey
Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product ofCurcuma longa(turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen.Keywords:melanoma;curcumin analog;apoptosis;oxidative stress;drug–drug interaction;tamoxifen;taxol;cisplatin
✓ 已验证
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2019
·Vol. 42
·期 6
·886-891
·
IF 1.54
Yangbiao He,Xujun Lang,Dong Cheng,Zhihao Yang
Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague–Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Kaili Wang,Chunjing Guo,Xue Dong,Yueming Yu,Bingjie Wang,Wanhui Liu,Daquan Chen
Many cancers, such as human breast cancer and lung cancer, easily metastasize to bones, leading to the formation of secondary tumors in advanced stages. On the basis of the CD44-targeted effect of oHA and the bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nanomicelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN-oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction. The CUR-loaded ALN-oHA-S-S-CUR micelles markedly inhibited the tumor growth. So the CUR-loaded ALN-oHA-S-S-CUR micelles constitute a promising drug delivery system for bone tumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2018
·
IF 8.537
Fengchun Huang,Li Xue,Huilin Zhang,Ruya Guo,Yanbin Li,Ming Liao,Maohua Wang,Jianhan Lin
In this study, an enzyme-free biosensor was developed for sensitive and specific detection of Salmonella typhimurium (S. typhimurium) using curcumin (CUR) as signal reporter and 1,2,4,5-tetrazine (Tz)-trans-cyclooctene (TCO) click chemistry for signal amplification. Methods: Nanoparticles composed of CUR and bovine serum albumin (BSA) were formulated and reacted with Tz and TCO to form Tz-TCO-CUR conjugates through Tz-TCO click chemistry. Then, the Tz-TCO-CUR conjugates were functionalized with polyclonal antibodies (pAbs) against S. typhimurium to form CUR-TCO-Tz-pAb conjugates. Magnetic nanoparticles (MNPs) conjugated with monoclonal antibodies (mAbs) against S. typhimurium through streptavidin-biotin binding were used to specifically and efficiently separate S. typhimurium from the background by magnetic separation. CUR-TCO-Tz-pAb conjugates were reacted with the magnetic bacteria to form CUR-Tz-TCO bacteria. Finally, CUR was released quickly from the CUR-Tz-TCO bacteria in the presence of NaOH, and the color change was measured at the characteristic wavelength of 468 nm for bacteria quantification. Results: A linear relationship between absorbance at 468 nm and concentration of S. typhimurium from 102 to 106 CFU/mL was found. The lower detection limit was calculated to be as low as 50 CFU/mL and the mean recovery was 107.47% for S. typhimurium in spiked chicken samples. Conclusion: This biosensor has the potential for practical applications in the detection of foodborne pathogens.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Xue Dong,Shaohua Zou,Chunjing Guo,Kaili Wang,Feng Zhao,Huaying Fan,Jungang Yin,Daquan Chen
The traditional therapy of cancer has systemic side effects, and many cancers, such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumours. This study was aimed at enhancing the anti-tumour effect of curcumin (CUR) and preventing tumour spread to the bone. A novel multifunctional redox-responsive and CD44 receptor targeting polymer-drug, poly alendronate-hyaluronan-S-S-curcumin copolymer (ALN-oHA-S-S-CUR) based CUR and alendronate (ALN) were synthesized successfully with the disulphide bond linker. The structure of ALN-oHA-S-S-CUR was characterized by 1H-NMR. The nanomedicine had natural anti-tumour drugs (CUR) as the hydrophobic kernel, and targeting CD44 receptor oligosaccharides of hyaluronan (oHA) and other anti-tumour drugs (ALN) as hydrophilic shell, named ALN-oHA-S-S-CUR conjugates, which could self-assemble into micelle-like nano-spheres in water via a dialysis method with hydrodynamic diameters of 179 ± 23 nm. Interestingly, the cur-loaded ALN-oHA-S-S-CUR micelles were stable in PBS but were capable of releasing the drug under the reducing environment. The rate of drug release was proportional to the GSH concentration. The uptake and cytotoxicity of micelles were higher in MDA-MB-231 cells than in MCF-7 cells because of a higher expression of the CD44 receptor in the former cell line. And compared to the cur-loaded oHA-CUR micelles, the cur-loaded ALN-oHA-S-S-CUR micelles had a good cellular uptake in 2D cancer cell and penetrability in 3D cancer cell spheroids. These results indicated the active targeting redox-sensitive micelles were promising as intracellular drug delivery systems for cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Wei Chen,Lin Li,Xiaofen Zhang,Yuan Liang,Zhijun Pu,Lingfeng Wang,Jingxin Mo
Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86 nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44+/CD133+ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2016
·Vol. 21
·期 8
·1061
·
IF 2.465
Chongshan Dai,Daowen Li,Lijing Gong,Xilong Xiao,Shusheng Tang
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.Keywords:curcumin;furazolidone;oxidative stress;DNA damage;mitochondrial pathway
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jie Liao,Xiaoming Li,Huiqi Yang,Wei He,Bingbing Wang,Shuyu Liu,Yubo Fan
Postoperative adhesion (POA) has emerged as a prevalent clinical challenge in soft tissue repair, emphasizing the critical need for preventive measures. However, the complex POA development process makes POA prevention from a single aspect insufficient. Hence, a curcumin-loaded poly-L-lactic acid-poly (caprolactone) micro-nano conjugated fibrous membrane (PAPC MCFM (cur)) is engineered to synergistically prevent POA from multiple perspectives, in which poly (caprolactone) (PCL) nanofibers (118 ± 12 nm) with low orientation traverse the oriented poly-L-lactic acid (PLLA) microfibers (2.0 ± 0.3 µm). The PAPC MCFM not only significantly improves the mechanical properties of the anisotropic fibrous membrane (AIFM) that the modulus of elasticity and the tensile strength in the direction vertical to microfiber orientation increase by 4.5 and 13.0 times, respectively, but also can further enhance the “contact guidance effect” of AIFM, i.e., hindering fibroblast adhesion, proliferation, and differentiation to myofibroblast through inhibiting integrin β1 activation, vinculin expression and focal adhesion (FA) formation, and the nuclear localization activation of yes-associated protein (YAP). Except for these effects, PAPC MCFM loading with 2.5 mg mL −1 curcumin can further prevent POA by delivering anti-inflammatory, antioxidant, and antibacterial properties, and by suppressing fibrosis through decreased transforming growth factor-β1(TGF-β1) expression, showing effective POA prevention in rat abdominal cavity and rabbit dura mater models.
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Kuo Zhao,Yilin Hao,Xin Guo,Yanjiao Chang,Xue Shen
Using of low-fat emulsion gels stabilized by quinoa protein (QP) for 3D food printing was limited by their defective rheological properties. The study was to explore the feasibility of using fucoidan (FU) to improve the printability and curcumin encapsulation stability of QP emulsion gel. The gels with 0.5–0.75 % FU incorporated were proved to be the most promising ink. Rheological analysis confirmed their great printing potential from the three-stages simulated 3D printing process. The incorporation of FU into emulsions induced more QP molecules adsorbed at the oil-water interface and smaller droplets size. When gel was induced by gluconate δ-lactone, these electrostatic interactions transformed into electrostatic attraction, resulting in a denser gel network. Adding FU to the gel improved its textural properties. Moreover, the gels with FU incorporated exerted better curcumin storage stability. This study provides a simple way to develop and improve the edible 3D printing inks for future food manufacturing.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jiahao Lin,Qiang Cai,Yinian Tang,Yanjun Xu,Qian Wang,Tingting Li,Huihao Xu,Shuaiyu Wang,Kai Fan,Zhongjie Liu,Yipeng Jin,Degui Lin
Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754 nm and particle size of 115 ± 15 nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10–15 nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50 mg MSNs, ratio of MSNs to lipid (w/w) = 1:1.11, and ratio of lipid to CHO (w/w) = 3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48 ± 2.73) %, (30.70 ± 3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Tang Weiwei,Huang Xiaomin,Yi Yun-Di,Cao Fan,Deng Manli,Fan Jiawei,Jiang Zheng-Xuan,Tao Li-Ming,Wang Xianwen,Shi Lei
Globally, uveitis is a collection of intraocular inflammatory disorders that affect mainly the uvea, resulting in irreversible blindness and a heavy socioeconomic burden. Excessive autoimmune inflammation and oxidative stress are major drivers that contribute to the initiation and progression of uveitis. Nevertheless, current therapeutic methods for uveitis are limited and are accompanied by several serious adverse effects. Recently, nanotechnology-based antioxidant strategies have provided novel options for the treatment of ocular diseases. Although curcumin (CUR) has prominent antioxidant capacity and reactive oxygen species (ROS) scavenging ability, its low bioavailability and undetermined mechanisms limit its extensive application. This investigation demonstrated that esterified hyaluronic acid-curcumin nanoparticles (HA-CUR NPs) with superior aqueous dispersion exhibited exceptional antioxidant enzyme mimetic activity, incorporating superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and free radical scavenging ability. Further in vitro and in vivo experimental results validated the protective function of HA-CUR NPs against oxidative stress-induced damage and inflammatory responses, attenuated pathological progression, relieved microvascular damage, and regulated fundus blood flow in retinal vascular networks. This may be attributable to the specific ability of HA-CUR NPs to target the CD44 receptor and activate the Keap1/Nrf2/HO-1 signaling pathway, suggesting a potential mechanism. In summary, this study revealed that HA-CUR NPs, which are composed of a natural product and biomacromolecules with outstanding artificial antioxidant enzyme activities, may be novel agents for effectively and safely treating uveitis and other ROS-related diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）