MOLECULES
·
2021
·Vol. 26
·期 18
·5698
·
IF 4.412
Sennan Qiao,Hansi Zhang,Fei Sun,Zhenyan Jiang
Artemisinin (also known as Qinghaosu), an active component of the Qinghao extract, is widely used as antimalarial drug. Previous studies reveal that artemisinin and its derivatives also have effective anti-inflammatory and immunomodulatory properties, but the direct molecular target remains unknown. Recently, several reports mentioned that myeloid differentiation factor 2 (MD-2, also known as lymphocyte antigen 96) may be the endogenous target of artemisinin in the inhibition of lipopolysaccharide signaling. However, the exact interaction between artemisinin and MD-2 is still not fully understood. Here, experimental and computational methods were employed to elucidate the relationship between the artemisinin and its inhibition mechanism. Experimental results showed that artemether exhibit higher anti-inflammatory activity performance than artemisinin and artesunate. Molecular docking results showed that artemisinin, artesunate, and artemether had similar binding poses, and all complexes remained stable throughout the whole molecular dynamics simulations, whereas the binding of artemisinin and its derivatives to MD-2 decreased the TLR4(Toll-Like Receptor 4)/MD-2 stability. Moreover, artemether exhibited lower binding energy as compared to artemisinin and artesunate, which is in good agreement with the experimental results. Leu61, Leu78, and Ile117 are indeed key residues that contribute to the binding free energy. Binding free energy analysis further confirmed that hydrophobic interactions were critical to maintain the binding mode of artemisinin and its derivatives with MD-2.Keywords:molecular dynamics simulation;myeloid differentiation factor 2;artemisinin;anti-inflammatory;binding free energy
研究领域:
药理学
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免疫学
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分子生物学
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计算化学
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产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2025
·Vol. 15
·期 6
·2657
·
IF 2.9
Weixing Zeng,Yawen Yang,Jia Xiong,Cui Li,Yang He,Zhihao Liang,Yongwen He
Fibroblasts can transform into cancer-associated fibroblasts (CAFs) when continuously stimulated by cancer cells, thereby playing a crucial role in cancer progression. Growing evidence indicates that targeted therapy for CAF can influence tumor progression. Dihydroartemisinin (DHA) and artemether (ARM), semisynthetic derivatives of the natural compound artemisinin, have exhibited anticancer effects in various tumors. In this study, we found that tumor cells secreted platelet-derived growth factor-BB (PDGF-BB), which stimulated fibroblasts to transition into the CAF phenotype (cell phenotype and secretory phenotype). CAFs promote Cal-27 cell proliferation by secreting lactate. We focused on the mechanisms by which DHA and ARM affect the tumor-stroma interactions. These findings demonstrated that DHA and ARM effectively suppressed the secretion of PDGF-BB from Cal-27 cells, maintaining the normal state of hOMF and preventing the proliferative effect on Cal-27 cells. These findings were confirmed in xenograft models. Our study showed that artemisinin derivatives prevent the progression of oral tongue squamous cell carcinoma (OTSCC) by inhibiting the production of PDGF-BB in cancer cells to maintain the normal state of fibroblasts, thus providing a potential avenue for targeted OTSCC treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGICAL METHODS
·
2024
·
IF 1.6
Fang Lu,Xiqun Wu,Fa Zhang,Jiaqiang Wu,Zhaodong Yuan,Baomin Wang,Guiyu Tan,Suqin Guo
Immunoassay relies on antibodies, but traditional antibodies such as monoclonal antibody (mAb) require animal immunization and complex procedures. Single-chain variable fragment (scFv) becomes a potential alternative to mAb with advantages of the low cost, rapid and easy prepared. In the present study, we prepared scFvs against dihydroartemisinin (DHA) based on E. coli and HEK293T cell expression system, named MBP-scFv and scFv-Fc, respectively. Their properties were compared with the parent mAb. The calculated affinity constants of mAb, MBP-scFv and scFv-Fc were 2.1 × 10 8 L mol −1 , 2.2 × 10 7 L mol −1 and 1.6 × 10 8 L mol −1 , respectively. The half inhibitory concentration (IC 50 ) of mAb, MBP-scFv and scFv-Fc were 1.16 ng mL −1 , 2.15 ng mL −1 and 6.57 ng mL −1 , respectively. Both the scFv showed less sensitive than the mAb based on the IC 50 . The cross-reactivities of MBP-scFv for artemisinin and artesunate exhibited similarities to the mAb, yet the cross-reactivities of scFv-Fc for these compounds exceeded those of the mAb significantly. The stability of the scFvs was ascertained to be maintained for over 5 days at room temperature, and for more than a month at both 4 °C and − 20 °C. After that, the indirect competitive enzyme-linked immunosorbent assays (icELISAs) based on the scFv from E. coli were used to detect the DHA content in eight drug samples, and the result was consistent with ultra-performance liquid chromatography simultaneously. Although scFv can be used for quantitative determination of drugs, but it still cannot completely replace mAb in immunoassay without evolution and modification.
研究领域:
免疫学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Shengli Quan,Jinhua Li,Shuxian Ding,Xingjie Zhuo,Yuanxiao Yang,Qin Li
Background Parkinson's disease is a progressive neurodegenerative disorder of the brain, that commonly leads to motor dysfunction and dementia. Artemether is a semi - synthetic derivative of artemisinin, which is extracted from the traditional Chinese herb Artemisia annua. And it is widely used in the treatment of malaria. Recent studies have shown that it exhibits significant neuroprotective effects and holds potential for the treatment of neurodegenerative diseases. However, its effects and mechanisms in the context of Parkinson 's disease remain unclear. Objective To explore Artemether's neuroprotective effects and mechanisms in 6-OHDA-induced PD models. Methods Network pharmacology and molecular docking were used to predict potential pathways and targets of Artemether against Parkinson's disease. PD models were established using 6-OHDA-induced PC12 cells and C57BL/6 mice to assess Artemether's effects and mechanisms. Results Through network pharmacological analysis and molecular docking verification, it was found that Artemether against Parkinson 's disease was related to apoptosis-related signaling pathways, and Artemether had good spontaneous binding activity with key targets PI3K, Akt, GSK-3β, and Bcl-2. Furthermore, the related experimental results showed that Artemether could increase the cell viability of PC12 cells induced by 6-OHDA, reduce intracellular ROS level, increase mitochondrial membrane potential and decrease apoptosis. In addition, Artemether improved motor dysfunction and cognitive dysfunction in Parkinson 's disease mice, and increased the expression of dopamine neurons in both the Substantia Nigra and Striatum. Conclusion Artemether exerted neuroprotective effects in Parkinson 's disease models in vitro and in vivo induced by 6-OHDA through the PI3K/Akt/GSK-3β signaling pathway.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Mengqi Bai,Li Qiang,Minjia Meng,Binrong Li,Suao Wang,Yilin Wu,Li Chen,Jiangdong Dai,Yan Liu,Jianming Pan
Molecularly imprinted membrane fabricated by conventional phase inversion method often suffers from low selectivity and low efficiency due to nonselective recognition sites resulted from usual swelling of the polymeric material and polymer-embedded imprinted sites. In this study, a new magnetic molecularly imprinted membrane (MMIM) with imprinted sites located and dispersed on the membrane up-surface was successfully prepared via phase inversion method by virtue of the magnetic field force for selective separation of Artemisinin (ART) and Artemether (ARE), in which magnetic imprinted particles coated by imprinted nanolayers with controllable thickness of ca. 10 nm were first synthesized and functioned as the original imprinted sites for the membrane. In comparison with the control membrane (MMIM0) without magnetic guidance, the magnetic molecularly imprinted membrane (MMIM1) exhibited significant enhancement in recognized adsorption and highly efficient separation for ART and ARE mixture owing to the imprinted sites concentrated on the up-surface. For the batch competitive permeation experiments, the value of β ART/ARE for MMIM reached up to 5.98, higher than that of MMIM0 ( β ART/ARE= 3.12). For the dynamic cross-flow separation system, the α value of MMIM1 in the initial time could be promoted to be 22.0, while that of MMIM0 was only α = 2.5. 1 H NMR spectra and density functional theory (DFT) verified that the enhanced selective separation efficiency for MMIM1 towards ART and ARE could be originated from both the shape of imprinted cavities and the interaction between ART and functional groups. This work highlights that the dynamic separation system over magnetic molecularly imprinted membrane provides an alternative potential “applicable platform” for large-scale separation and extraction of natural products.
研究领域:
化学工程
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生物技术
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药物化学
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产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2021
·Vol. 179
·期 9
·1962-1977
·
IF 8.74
Jianxin Jia,Qi Kang,Shunzhi Liu,Yabin Song,Florence Susan Wong,Yingkun Qiu,Mingyu Li
Background and Purpose Recently, the antimalarial drug, artemether and the neurotransmitter GABA were identified to convert alpha cells into beta-like cells in vivo . However, some of these observations were challenged by other studies. To help address the controversy, we took advantage of zebrafish as a model to perform this study. Experimental Approach First, we performed a small-molecule screening for artemether and its skeleton analogues. Second, we used the Cre-LoxP system for lineage tracing to indicate the conversion of alpha cells into beta cells in vivo . The stable transgenic ins2:eGFP αTC1-6-cell line was used for evaluation of alpha-cell transdifferentiation in vitro . We further used multiple zebrafish transgenic and mutation lines to demonstrate beta-cell differentiation, beta-cell ablation and alpha-cell hyperplasia in this study. Key Results We showed that artemether and another sesquiterpene, aspterric acid, induced alpha-cell transdifferentiation into beta cells, both in zebrafish as well as using αTC1-6 cells. Furthermore, these two compounds also converted alpha cells into beta cells when beta cells were lost or alpha cells were hyperplastic in zebrafish. Unlike the previous report, the conversion of alpha cells to beta cells was mediated by increasing Pax4 expression, but not suppression of Arx expression. Conclusion and Implications Our data suggest that in zebrafish and αTC1-6 cells, both artemether and aspterric acid induce alpha-cell transdifferentiation. Our data, along with those of Li et al. (2017), suggested that artemether and aspterric acid were able to induce alpha-cell transdifferentiation, at least in zebrafish and αTC1-6 cells. Graphical Artemether and aspterric acid induced alpha-cell to beta-cell conversion but did not induced progenitor cell differentiation or exiting beta replication. The conversion of alpha cells to beta cells was mediated by increasing Pax4 expression.
研究领域:
药理学
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发育生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2020
·
IF 7.635
Yilin Wu,Wendong Xing,Minjia Meng,Jian Lu,Faguang Ma,Jia Gao,Xinyu Lin,Chao Yu
Development of membrane-associated molecularly imprinted materials with fast and high permselectivity has been significant needed in separation engineering field. Herein, for the first time, a subversive synthesis strategy with hierarchical structure was proposed for the preparation of nanocomposite blended molecularly imprinted membranes (NBMIMs). Artemisinin, the high-efficiency antimalarial drug, was chosen as the template molecule. Instead of the direct modification of nanocomposite on membrane surfaces , the double-bonded TiO 2 @PDA was initially prepared, the blended membrane synthesis procedure was then conducted through a phase conversion process by using the as-prepared TiO 2 @PDA and PVDF powder as host materials. Importantly, the double-bonded TiO 2 @PDA-based nanocomposite in blended membranes was first proposed and applied as imprinting-initiated factor during the next artemisinin-imprinted process, leading the formation of imitated core-shell structure on membrane surfaces. It was no surprise that more excellent rebinding capacity (66.9 mg g −1 ), fast adsorption kinetics and high permselectivity coefficients (more than 17) were successfully achieved. Furthermore, an important conclusion was also obtained that TiO 2 @PDA-based nanocomposite from NBMIMs would cause significant enhancement of the rebinding capacity, that is to say, more and more artemisinin-imprinted sites would be synthesized by increasing the dosage of TiO 2 @PDA until 0.5 g. Therefore, a novel direction for the design and manipulation of MIMs materials had been successfully designed and guided for selective separation of artemisinin.
研究领域:
分离工程
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材料科学
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2018
·Vol. 37
·期 1
·1-14
·
IF 6.217
Yao Yuyuan,Guo Qinglong,Cao Yue,Qiu Yangmin,Tan Renxiang,Yu Zhou,Zhou Yuxin,Lu Na
Background Cancer-associated fibroblasts (CAFs) are activated fibroblasts associated with cancer. They have an important role in tumor growth and metastasis. Artemisinin (ART) is a sesquiterpene lactone extracted from Chinese herb qinghao, and artemether (ARM), artesunate (ARS) and dihydroartemisinin (DHA) were synthesized derivatives of artemisinin, which also have anti-malarial and anti-cancer effects such as artemisinin.Methods In this study, we investigated the in-vitro and in-vivo effects of artemisinin derivatives on inactivating cancer-associated fibroblasts and uncovered its underlying mechanism.Results We demonstrated that ARS and DHA could revert L-929-CAFs and CAFs from activated to inactivated state in vitro. Mechanically, ARS and DHA could suppress TGF-β signaling to inhibit activation of L-929-CAFs and CAFs, and decreased interaction between tumor and tumor microenvironment. The results showed that ARS and DHA could suppress CAFs-induced breast cancer growth and metastasis in the orthotopic model. Conformably, ARS and DHA suppressed TGF-β signaling to inactivate cancer-associated fibroblasts and inhibit cancer metastasis in vivo.Conclusion sArtemisinin derivatives are potential therapeutic agents for the treatment of breast cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
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2016
·Vol. 11
·期 10
·e0164842
·
IF 3.057
Shoubing Wang,Ziran Xu
Increased eutrophication in the recent years has resulted in considerable research focus on identification of methods for preventing cyanobacterial blooms that are rapid and efficient. The objectives of this study were to investigate the effects of dihydroartemisinin and artemether on the growth of Microcystis aeruginosa and to elucidate its mode of action. Variations in cell density, chlorophyll a, soluble protein, malondialdehyde, extracellular alkaline phosphatase activity (APA), and chlorophyll fluorescence parameters (Fv/Fm, ΦPSII, ETR, rapid light curves, fast chlorophyll fluorescence curves on fluorescence intensity, and relative variable fluorescence) were evaluated by lab-cultured experiments. Our results demonstrated that both dihydroartemisinin and artemether inhibited the growth of M . aeruginosa by impairing the photosynthetic center in photosystem II and reducing extracellular APA, with a higher sensitivity exhibited toward artemether. The inhibitory effects of dihydroartemisinin on M . aeruginosa increased with concentration, and the maximum growth inhibitory rate was 42.17% at 24 mg·L -1 after 120h exposure, whereas it was 55.72% at 6 mg·L -1 artemetherafter 120h exposure. Moreover, the chlorophyll fluorescence was significantly inhibited (p<0.05) after 120h exposure to 12 and 24 mg·L -1 dihydroartemisinin. Furthermore, after 120h exposure to 6 mg·L -1 artemether, Fv/Fm, ΦPSII, ETR and rETR max showed a significant decrease (p<0.01) from initial values of 0.490, 0.516, 17.333, and 104.800, respectively, to 0. One-way analysis of variance showed that 6 mg·L -1 artemether and 24 mg·L -1 dihydroartemisinin had significant inhibitory effects on extracellular APA (p<0.01). The results of this study would be useful to further studies to validate the feasibility of dihydroartemisinin and artemether treatment to inhibit overall cyanobacterial growth in water bodies, before this can be put into practice.
研究领域:
环境科学
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水生生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Xuerong Dong,Xiang Zhang,Manyuan Wang,Liwei Gu,Jing Li,Muxin Gong
Heme is a prosthetic group of hemoglobin comprising protoporphyrin IX (PPIX) with Fe 2+ . Studies have shown that modulating heme synthesis pathway in Plasmodium could greatly affect the action mechanism and antimalarial effect of artemisinin and its derivatives. Herein, an intraerythrocytic parasite targeted nanostructured lipid carrier (NLC) was developed for potentiation of artemether (ARM) by combination with PPIX and iron-loaded transferrin (holo-Tf). Firstly, ARM and PPIX were co-loaded into NLCs with high entrapment efficiency. Then, a targeting ligand heparin (HP) was electrostatically adsorbed onto the periphery of NLCs, followed by conjugation with holo-Tf to receive the final formulation Tf-HP-NLC/ARM/PPIX. Tf-HP-NLC/ARM/PPIX exhibited nanoscale particle size (~188 nm) and was relatively stable in simulated gastrointestinal fluids and rat plasma. A sustained drug release characteristic was observed in PBS (pH 7.4). In vitro targeting assay confirmed that Tf-HP-NLC/ARM/PPIX could be specifically and efficiently internalized into intraerythrocytic parasites via HP receptor-meditated endocytosis. Furthermore, due to enhanced intraparasitic accumulation and activated mechanism of ARM, the combinational delivery system Tf-HP-NLC/ARM/PPIX showed increased inhibitory activity against Plasmodium falciparum in culture and enhanced antimalarial effect in Plasmodium berghei -infected murine model, suggesting a promising strategy for development of new therapy based on action mechanism of ARM.
研究领域:
药剂学
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寄生虫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2015
·
IF 5.056
Yilin Wu,Xinlin Liu,Minjia Meng,Peng Lv,Ming Yan,Xiao Wei,Hongji Li,Yongsheng Yan,Chunxiang Li
Inspired from the highly bioadhesive performance of mussel protein, a straightforward synthetic method for highly dense imprinting of artemisinin (Ars) was developed to prepare bio-inspired porous molecularly imprinted nanocomposite membranes (MINCMs). The key design for the successful synthesis of MINCMs is the formation of an organic–inorganic hybrid structure at the surface of polydopamine-modified regenerated cellulose membranes (PDA@RCMs). In this regard, the polydopamine coating surfaces could be used as a versatile platform for the further coating of inorganic nanoparticles . After a bio-inspired adhesion process, a larger active surface area and layered structure could be obtained at the surface of PDA@RCMs, hence promoting the preparation of the novel MINCMs with excellent perm-selectivity performance and regeneration ability. Moreover, the as-prepared MINCMs not only exhibited an outstanding adsorption capacity (54 mg g −1 ), but also showed an excellent perm-selectivity (separation factor β is 15.03) toward Ars, which is promising for Ars separation and purification.
研究领域:
材料科学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
LANGMUIR
·
2014
·
IF 4.384
Yilin Wu,Ming Yan,Yongsheng Yan,Xinlin Liu,Minjia Meng,Peng Lv,Jianming Pan,Pengwei Huo,Chunxiang Li
Inspired by a surface functional monomer-directing prepolymerization system, a straightforward and effective synthesis method was first developed to prepare highly regenerate and perm-selective molecularly imprinted composite membranes of artemisinin (Ars) molecules. Attributing to the formation of the prepolymerization system, Ars molecules are attracted and bound to the membrane surface, hence promoting the growth of homogeneous and high-density molecular recognition sites on the surface of membrane materials. Afterward, a two-step-temperature imprinting procedure was carried out to prepare the novel surface functional monomer capping molecularly imprinted membranes (FMIMs). The as-prepared FMIMs not only exhibited highly adsorption capacity (11.91 mg g–1) but also showed an outstanding specific selectivity (imprinting factor α is 4.50) and excellent perm-selectivity ability (separation factor β is 10.60) toward Ars molecules, which is promising for Ars separation and purification.
研究领域:
材料科学
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药物化学
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分离技术
✓ 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）