JOURNAL OF SEPARATION SCIENCE
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2018
·Vol. 41
·期 16
·3318-3327
·
IF 2.415
Ming Zhong,Yan-Hong Wang,Lu Wang,Rui-Qing Long,Chun-Lin Chen
A novel type of magnetic molecularly imprinted polymer was prepared for the selective enrichment and isolation of chelerythrine from Macleaya cordata (Willd) R. Br . The magnetic molecularly imprinted polymers were prepared using functional Fe 3 O 4 @SiO 2 as a magnetic support, chelerythrine as template, methacrylic acid as functional monomer, and ethylene glycol dimethacrylate as cross-linker. Density functional theory at the B3LYP/6-31G (d, p) level with Gaussian 09 software was applied to calculate the interaction energies of chelerythrine, methacrylic acid and the complexes formed from chelerythrine and methacrylic acid in different ratios. The structural features and morphology of the synthesized polymers were characterized by using Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and vibration sample magnetometry. Adsorption experiments revealed that the magnetic molecularly imprinted polymers possessed rapid kinetics, high selectivity, and a higher binding capacity (7.96 mg/g) to chelerythrine than magnetic molecularly non-imprinted polymers (2.36 mg/g). The adsorption process was in good agreement with the Langmuir adsorption isotherm and pseudo-second-order kinetics models. Furthermore, the magnetic molecularly imprinted polymers were successfully employed as adsorbents for the extraction and enrichment of chelerythrine from Macleaya cordata (Willd) R. Br . The results indicated that the magnetic molecularly imprinted polymers were suitable for the selective adsorption of chelerythrine from complex samples such as natural medical plants.
研究领域:
药学
·
分析化学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2019
·Vol. 24
·期 1
·50-60
·
IF 4.658
Hongchao He,Ran Zhuo,Jun Dai,Xiaojing Wang,Xin Huang,Haofei Wang,Danfeng Xu
Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad-range protein kinase C inhibitor which has anti-cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose-dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE-induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS-caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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药理学
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DOI
PubMed
高影响因子
Journal of Herbal Medicine
·
2023
·
IF 2.3
Ying Liu,Xia Zhang,Huaiyu Cheng,Yifang Li,Guangxiong Zhou
ABSTRACT Introduction It has a long history to employ Macleaya cordata (Willd.) R. Br. (Papaveraceae) for the treatment of a variety of diseases in China. Chelerythrine, one of the major of M. cordata with detoxifying and anti-inflammatory effect, is reported to combat bacteria and fungus. This work aims to explore the effect of chelerythrine against fluconazole-resistant C. albicans and also illustrate its potential mechanism. Methods The microdilution method, following CLSI-M27-A3 was used to evaluate the effect of chelerythrine against fluconazole-resistant C. albicans. Meanwhile, biofilm viability was assessed by XTT assay and cell morphology was observed by inverted microscope. RT-qPCR and confocal laser scanning microscope were employed to detect the mRNA expression and DCFH-DA staining, respectively. Fluorescence intensity was quantified by flow cytometry. Results The total alkaloids extract of M. cordata significantly inhibited the viability of C. albicans, concentration of which in 64 μg/mL presented to 40% inhibitory effect . In addition, the MIC 80 for chelerythrine was 8 μM, whereas chelerythrine in 4 μM inhibited biofilm formation by 47.7%. Further studies revealed that chelerythrine reduced the hydrophobicity of cellular surface, inhibited hyphal growth, downregulated the expression of genes related to cAMP pathway, increased cellular permeability and promoted the production of reactive oxygen species (ROS). Conclusion Chelerythrine inhibited biofilm formation by decreasing CSH and inhibiting the cAMP pathway. Chelerythrine increased cellular permeability and promoted the production of reactive oxygen species, which leads to the cell death of fluconazole-resistant C. albicans .
研究领域:
药理学
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微生物学
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植物化学
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抗真菌研究
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DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Lijun Huang,Yuliang Liu,Xingxin Sheng,Yongbo Zhu,Xinyi Li,Meng Liang,Hao Xie,Ming Zhong,Binbin Zhou
A novel MOFs hydrogel composite (MIP-CuMOFs@SA-CS) was created by integrating a molecularly imprinted metal–organic framework (MIP-CuMOFs) within a scaffold of sodium alginate-chitosan (SA-CS(Cu 2+ )). The MIP-CuMOFs@SA-CS served as a recognition element to construct an electrochemical sensor for the detection of trace amounts of chelerythrine (CHE). Reduced graphene oxide (rGO) and reduced graphene nanoribbons (rGNRs) were employed for electrode modification and served as the sensing platform. It was to enhance the stability and sensitivity attributes of the sensor system. The signal probe of copper hexacyanoferrate (CuHCF) was generated through the chemical reaction involving Cu 2+ within the composite structure of MIP-CuMOFs@SA-CS with potassium ferricyanide. The experimental results showed that the constructed sensor has a good linear relationship (50 ∼ 500 nmol L −1 ) and a low detection limit (13.83 nmol L −1 ). Moreover, the sensor exhibited good selectivity, recovery rates, and repeatability (RSD = 2.81 %). With the subjected to spiked serum samples, the demonstrating recovery percentages were in the range of 97.17 % to 101.73 %. The CHE molecularly imprinted electrochemical sensor constructed is capable of detecting trace amounts of CHE with the advantages of simplicity, rapidity, high sensitivity, and low cost, which provides a useful reference for the detection of low concentrations of CHE.
研究领域:
分析化学
·
材料科学
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生物医学工程
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DOI
高影响因子
Analytical Methods
·
2013
·Vol. 5
·期 19
·5309-5316
·
IF 1.855
Yizhong Shen,Shaopu Liu,Jian Wang,Dan Li,Xiaodan Wang,Youqiu He
A sensitive and simple method for the determination of chelerythrine (CHE) was developed based on the fluorescence quenching effect of CHE for glutathione (GSH)-capped CdTe/CdS quantum dots (QDs). Under optimum conditions, a good linear relationship was obtained from 0.073 to 24.0 μg mL−1 with a correlation coefficient of 0.9988, and the detection limit (3σ/κ) was 21.9 ng mL−1. The fluorescence quenching mechanism that has been proposed is based on electron transfer supported by ultraviolet-visible (UV-vis) absorption, fluorescence (FL) spectroscopy and electrochemical techniques. The method has been applied to the determination of CHE in synthetic samples and fresh serum samples from healthy humans with satisfactory results. The proposed method manifested several advantages such as high sensitivity, short analysis time, low cost and ease of operation.
研究领域:
分析化学
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生物医学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2020
·
IF 5.573
Bohang Zhou,Hui Li,Zhiming Cui,Ding Li,Huiling Geng,Jinming Gao,Le Zhou
As simple analogues of the natural compound chelerythrine , a novel anti-cholinesterase 2-phenylisoquinolin-2-ium scaffold was designed by structure imitation. The activity evaluation led to the discovery of seven compounds with potent anti-acetylcholinesterase activity with IC 50 values of ≤0.72 μM, superior to chelerythrine and standard drugs galantamine . Particularly, compound 8y showed the excellent dual acetylcholinesterase-butyrylcholinesterase inhibition activity, superior to rivastigmine , a dual cholinesterase inhibitor drug. Furthermore, the compounds displayed a competitive anti-acetylcholinesterase mechanism with the substrate and low cytotoxicity. Molecular docking showed that the isoquinoline moiety is embedded in a cavity surrounded by four aromatic residues of acetylcholinesterase by the π-π action. Structure-activity relationship showed that the p -substituents on the C-ring can dramatically improve the anti-acetylcholinesterase activity, while 8-OMe can increase the activity against the two cholinesterases simultaneously. Thus, the title compounds emerged as promising lead compounds for the development of novel cholinesterase inhibitor agents.
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DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 9
·1837
·
IF 7.675
Yanling Lin,Qinzhi Zhang,Baofu Xie,Haiyang Jiang,Jianzhong Shen,Shusheng Tang,Chongshan Dai
Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient inChelidonium majusthat could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.Keywords:chelerythrine;oxidative stress;apoptosis;mitochondrial apoptotic pathway;Akt pathway
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 19
·6842
·
IF 4.6
Minghui Liu,Shibo Sun,Yao Meng,Ling Wang,Haowen Liu,Wuyang Shi,Qiuyu Zhang,Weiping Xu,Bingbing Sun,Jianqiang Xu
Targeting thioredoxin reductase (TXNRD) with low-weight molecules is emerging as a high-efficacy anti-cancer strategy in chemotherapy. Sanguinarine has been reported to inhibit the activity of TXNRD1, indicating that benzophenanthridine alkaloid is a fascinating chemical entity in the field of TXNRD1 inhibitors. In this study, the inhibition of three benzophenanthridine alkaloids, including chelerythrine, sanguinarine, and nitidine, on recombinant TXNRD1 was investigated, and their anti-cancer mechanisms were revealed using three gastric cancer cell lines. Chelerythrine and sanguinarine are more potent inhibitors of TXNRD1 than nitidine, and the inhibitory effects take place in a dose- and time-dependent manner. Site-directed mutagenesis of TXNRD1 and in vitro inhibition analysis proved that chelerythrine or sanguinarine is primarily bound to the Sec498residue of the enzyme, but the neighboring Cys497and remaining N-terminal redox-active cysteines could also be modified after the conjugation of Sec498. With high similarity to sanguinarine, chelerythrine exhibited cytotoxic effects on multiple gastric cancer cell lines and suppressed the proliferation of tumor spheroids derived from NCI-N87 cells. Chelerythrine elevated cellular levels of reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress. Moreover, the ROS induced by chelerythrine could be completely suppressed by the addition ofN-acetyl-L-cysteine (NAC), and the same is true for sanguinarine. Notably, Nec-1, an RIPK1 inhibitor, rescued the chelerythrine-induced rapid cell death, indicating that chelerythrine triggers necroptosis in gastric cancer cells. Taken together, this study demonstrates that chelerythrine is a novel inhibitor of TXNRD1 by targeting Sec498and possessing high anti-tumor properties on multiple gastric cancer cell lines by eliciting necroptosis.Keywords:thioredoxin reductase;chelerythrine;sanguinarine;necroptosis;gastric cancer;selenocysteine
研究领域:
肿瘤学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
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