MOLECULES
·
2014
·Vol. 19
·期 6
·7287-7307
·
IF 2.095
Yali Zhang,Leping Zhao,Jianzhang Wu,Xin Jiang,Lili Dong,Fengli Xu,Peng Zou,Yuanrong Dai,Xiaoou Shan,Shulin Yang,Guang Liang
Curcumin has been reported to possess multiple bioactivities, such as antioxidant, anticancer, and anti-inflammatory properties, however the clinical application of curcumin has been significantly limited by its instability and poor metabolism. Modification of curcumin has led to discovery and development of lots of novel therapeutic candidates. In recent years acute and chronic inflammation has been the focus of numerous studies in various diseases. Here, we synthesized a series of asymmetrical curcumin analogs with highin vitrochemical stability, and their anti-inflammatory activity was evaluated in LPS-stimulated macrophages. According to the bio-screening results and QSAR analysis, these analogs exhibited potent activities against LPS-induced TNF-α and IL-6 release. Among the analogs of the potent anti-inflammatory activity, compounds3b8and3b9exhibited significant protection and possess enhanced anti-inflammatory activity thereby attenuated the LPS-induced septic death in mice.Keywords:curcumin;asymmetrical curcumin analogs;anti-inflammation;QSAR;cytokines
研究领域:
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 13
·2252-2261
·
IF 3.614
Li Yang,Li-yuan Xie,Xuan Chen,Xiao-hong Bai,Shuang Hu
A novel solvent terminated microextraction method based on a natural deep eutectic solvent (L-menthol and lactic acid at a molar ratio of 1:2) coupled with high-performance liquid chromatography was proposed, which was utilized for the separation and enrichment of bisdemethoxycurcumin, demethoxycurcumin and curcumin in Curcumae Longae Rhizoma and turmeric tea. The effects of independent parameters on extraction efficiency were optimized by single-factor analysis. Subsequently, four predominated parameters affecting the extraction procedure, including extractant volume, salt concentration, demulsifier consumption, and demulsification time, were further evaluated by a central composite design. Under the optimized conditions, the linear ranges of calibration curves were 0.005–0.5 μg/mL for bisdemethoxycurcumin, 0.004–0.4 μg/mL for demethoxycurcumin, and 0.0045–0.45 μg/mL for curcumin, respectively. In addition, the developed method provided low detection limits (0.1–0.4 ng/mL) and high enrichment factors (279–350). Its intra-day and inter-day precision were carried out by relative standard deviation ranging from 2.2 to 9.2%. Finally, the applicability of this method was assessed by the analysis of Curcumae Longae Rhizoma and turmeric tea samples. The results showed that these samples were detected successfully and the spiked recoveries over the range of 85.3-108.9% with relative standard deviations of 1.6-8.9% were attained, indicating its high relative recoveries with good precision in real sample analysis.
研究领域:
分析化学
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药物分析
·
天然产物化学
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中药质量控制
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样品前处理
·
药物代谢
✓ 已验证
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Mingyue Zhou,Xuan Wu,Yan Li,Huixia Zhang,Qinghua Liu,Linlin Song,Caiyun Wang,Betty Yuen Kwan Law,Zhihong Jiang,Wei Zhang
Alzheimer’s disease (AD) is a neurodegenerative disease associated with aging, and the number of people affected is rapidly increasing. Abnormally hyperphosphorylated tau filaments and extracellular deposits of amyloid β-peptides (Aβ) fibrils are two important pathological hallmarks of AD. Currently, stopping the production of Aβ and blocking its aggregation is the main strategy for the treatment of AD. Turmeric is effective in treating neurodegenerative diseases, but there is no effective way to identify active compounds from their complicated chemical compositions. Instead of using conventional extraction and separation methods with low efficiency and time-consuming, our group tried to use atomic materials in high-throughput chemical screening due to their structural characteristics and the unique advantages of surface atomic. Herein, a novel atomic zinc sites with hierarchical porous carbon (Zn-HPC) was synthesized to quickly screen potential inhibitors of Aβ aggregation in turmeric. As-combined Aβ@Zn-HPC demonstrates superior storage stability and high selectivity, outperforming the most reported supporters for ligand fishing. Five compounds with strong affinity on Aβ@Zn-HPC were selected by high-performance liquid chromatography-hybrid linear ion trap/orbitrap mass spectrometer after incubation with turmeric extract. Finally, it was shown that curcumin and bisdemethoxycurcumin can inhibit Aβ aggregation by using thioflavin-T fluorescence assay and biolayer interferometry. A new application for the accurate identification of Aβ aggregation inhibitors from turmeric were developed based on the active compounds possessing binding affinity to Aβ to inhibit its aggregation. The developed method could provide a promising tool for efficient drug discovery from natural product resources.
研究领域:
材料科学
·
神经科学
·
药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jiaying Hao,Yunju Zhang,Kaiwei Liu,Boyu Zhang,Hao Wang,Yuning Jin,Bin Wang,Di Wang,Ying Li,Xueli Wei,Qinyuan Ma,Xiuzhen Gao
Tetrahydrocurcumin (THC), a major bioactive metabolite of curcumin, exhibits superior bioavailability and stability, making it a highly sought-after ingredient for nutraceutical and functional food applications. Current chemical and microbial THC production methods both suffer from selectivity issues and require complex purification steps. Here, we developed an enzymatic platform for THC biosynthesis through systematic enzyme discovery and engineering. We mined and identified a novel enzyme from Kosakonia cowanii with a good soluble expression. Structure-guided design yielded a triple mutant, M3 (K274L/P266F/Q286Y), with an 8.14-fold enhanced catalytic efficiency. Molecular dynamics simulations and binding free energy analysis revealed that mutations synergistically enhanced substrate binding and optimized the catalytic environment through both local conformational changes and intersubunit interactions. In a preparative-scale synthesis, M3 achieved 99.7% conversion of 50 mM curcumin within 3 h, yielding 17.56 g/L of THC. This enzymatic approach eliminates toxic metals and complex purification procedures, providing a sustainable alternative for industrial THC production.
研究领域:
生物化学
·
酶学
·
合成生物学
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药物代谢
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分子生物学
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绿色化学
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功能食品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 4
·448
·
IF 4.8
Xueli Guo,Zhongyan Liu,Lina Wu,Pan Guo
Background : Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods : A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w / w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results : The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug ( p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls ( p < 0.001), leading to 58.7% tumor volume reduction ( p < 0.001). Conclusions : The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
·
2024
·Vol. 22
·期 4
·479-491
·
IF 2.8
Teng Guo,Chenming Zhang,Yuling Chen,Yihan Wu,Zhenda Liu,Yongtai Zhang,Nianping Feng
BackgroundAdding a suitable surfactant can enhance the transdermal permeability of transethosomes while also leveraging its functionality as a functional material. In this study, transethosomes were prepared using D-α-tocopherol acid polyethylene glycol succinate (TPGS) as edge activators for transdermal delivery of curcumin (Cur).MethodsThe TPGS-mediated curcumin-loaded transethosomes (Cur@TES) were prepared and formulated optimally, and the optimized formulations were characterized for their morphology, particle size, entrapment efficiency (EE) and drug loading (DL). The stability and deformability of Cur@TES were investigated, while the transdermal delivery of Cur@TES was investigated through in vitro transdermal assays and fluorescence imaging. A mouse ear swelling model was performed to determine the anti-inflammatory effect of Cur@TES.ResultsCur@TES appeared round or elliptical in shape. The particle size, EE and DL for the optimized formulation were observed as 131.2 ± 7.2 nm, 97.68 ± 2.26%, and 6.58 ± 0.62%, respectively. X-ray diffraction analysis confirmed the formation of disordered structures in the inner core of the vesicles. Moreover, Cur@TES system demonstrated better stability and deformability compared to the curcumin-loaded ethosomes (Cur@ES). In vitro transdermal experiments demonstrated that Cur@TES significantly increased the amount of drug retained in the skin (P<0.05). Fluorescence imaging confirmed that the skin distribution was distinctly enhanced with the delivery by TPGS mediated transethosomes. In addition, Cur@TES showed a significant inhibitory effect on Inflammatory swelling in the mouse ear-swelling model.ConclusionTPGS-mediated transethosomes exhibit significant transdermal advantages and enhanced anti-inflammatory effects, providing a new perspective for the transdermal delivery of curcumin.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2013
·
IF 1.206
Cheng Yang,Keng Wu,Shang-Hai Li,Qiong You
Context: The heart is one of the target organs susceptible to attack by sepsis, and protection of the cardiac function in sepsis or alleviation dysfunction caused by sepsis appears a serious and urgent problem.Objective: This study was designed to explore the effect of curcumin on myocardial injury induced by sepsis and to explore the therapeutic effect of curcumin in managing sepsis induced cardiac dysfunction.Methods: Cecal ligation and puncture surgery were used to establish the sepsis model. Curcumin was administered by peritoneal injection (200 mg/kg/d, 3 days). The effects of curcumin on the cardiac functions [Ejection Fraction (EF), Fractional Shortening (FS), Cardiac Output (CO), Heart Rate (HR)], body temperature, cTn I and superoxide dismutase levels, malondialdehyde content (an index of lipid peroxidation), and myocardial histopathological and ultrastructural studies were carried out.Results: We demonstrated that treatment of rats with curcumin significantly decreased elevated levels of cTn I and MDA (p < 0.05) in plasma, and increase the levels of SOD (p < 0.05) after CLP. Moreover, curcumin markedly enhanced the myocardial contractility by increasing the decreased EF and FS in rats with sepsis induced by CLP (p < 0.05). In addition, curcumin could alleviate the myocardial inflammation and structure damage of myocardial cells in sepsis induced by CLP.Conclusion: In conclusion, the results from the present study demonstrate that curcumin has the protective effects on cardiac function in rats with sepsis and curcumin could be considered as an effective and safe therapeutic agent for the management of sepsis induced cardiac dysfunction.
研究领域:
医学
·
药理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2022
·
IF 9.336
Hualin Dong,Peng Wang,Zongyun Yang,Ru Li,Xinglian Xu,Juan Shen
Ultrasound has a recognized ability to modulate the structure and function of proteins. Discovering the influential mechanism of ultrasound on the intramolecular interactions of egg-white protein isolate–curcumin ( EPI –Cur) nanoparticles and their intermolecular interaction during freeze drying and redispersion is meaningful. In this study, under the extension of pre-sonication time, the protein solubility, surface hydrophobicity, and curcumin encapsulation rate showed an increasing trend, reaching the highest value at 12 min of treatment. However, the values decreased under the followed extension of ultrasound time. After freeze drying and redispersion were applied, the EPI –Cur sample under 12 min of ultrasound treatment exhibited minimal aggregation degree and loss of curcumin. The retention and loading rates of curcumin in the lyophilized powder reached 96 % and 33.60 mg/g EPI , respectively. However, under excessive ultrasound of >12 min, scanning electron microscopy showed distinct blocky aggregates. Overexposure of the hydrophobic region of the protein triggered protein-mediated hydrophobic aggregation after freeze drying. X-ray diffraction patterns showed the highest crystallinity, indicating that the free curcumin-mediated hydrophobic aggregation during freeze drying was enhanced by the concentration effect and intensified the formation of larger aggregates. This work has practical significance for developing the delivery of hydrophobic active substances. It provides theoretical value for the dynamic dispersity change in protein-hydrophobic active substances during freeze drying and redissolving.
研究领域:
食品科学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING & TECHNOLOGY
·
2024
·Vol. 47
·期 10
·e202400203
·
IF 1.8
Jinwei Qi,Jihui Li,Kaili Liu,Huixin Zhang,Jian Han,Jianxin Chen
The curcumin-malic acid-aspartic acid polymer (PCMA) as a new water treatment agent was prepared by solid phase synthesis of curcumin, malic acid and aspartic acid. The static scale inhibition experiments showed that PCMA can inhibit CaCO 3 and CaSO 4 scale formation by 100.0 % and had excellent scale inhibition effect under various experimental conditions. The mechanism of action of PCMA was obtained by X-ray diffraction, scanning electron microscope and molecular dynamics simulation. Electrochemical test showed that PCMA is an anodic corrosion inhibitor that achieves 93.1 % corrosion inhibition by forming a protective film on the surface of Q235 carbon steel. Besides, fluorescence spectra proved that PCMA has stable fluorescence intensity.
研究领域:
材料科学
·
化学工程
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Hui-Yun Zhang,Cong-yong Sun,Michael Adu-Frimpong,Jiang-nan Yu,Xi-ming Xu
The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Cihui Tian,Sajid Asghar,Yurui Xu,Zhipeng Chen,Mei Zhang,Lin Huang,Junxiu Ye,Qineng Ping,Yanyu Xiao
In this study, a redox-sensitive glioma-targeting micelle system was designed to deliver curcumin (CUR) by conjugating it to hyaluronic acid (HA-s-s-CUR, HSC) via disulfide linkage. The effect of the molecular weight of HA on the physicochemical characteristics of HSC conjugates and their in vitro effects in glioma cells were also explored. These conjugates formed nano-scale micelles (209–926 nm) independently in aqueous solution. The micelles greatly increased the solubility of CUR and improved its stability, which is crucial for harnessing the therapeutic potential of this active molecule. The redox sensitivities of different HSC micelles were measured by using a dynamic light scattering method and in vitro release assay, which showed that the low (50 kDa) and medium molecular weight (200 kDa and 500 kD) HA-based conjugates were sensitive to GSH, whereas higher molecular weights (1000 kDa and 2000 kDa) did not show redox-sensitivity. Increased cytotoxicity and uptake of low and medium molecular weight-modified HSC conjugates by the glioma cells further confirmed that the sensitive micelles are more effective for intracellular drug delivery compared to the high molecular weight-modified HSC conjugates or the plain CUR . In summary, the molecular weight of HA affects the physicochemical attributes of HSC conjugates. Only HSC micelles made with HA molecules less than 500 kDa exhibit redox sensitivity.
研究领域:
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 5
·389
·
IF 4.4
Feng Gao,Wenyu Liang,Qixin Chen,Bairu Chen,Yuchen Liu,Zhibo Liu,Xu Xu,Rongrong Zhu,Liming Cheng
Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal–phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.Keywords:nanozyme;ROS scavenging;anti-inflammatory;neuroprotective
研究领域:
纳米技术
·
神经科学
·
药理学
✓ 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）