TALANTA
·
2018
·
IF 4.244
Xiao-Chong Tang,Yi Xiao,Ping Li,Lian-Wen Qi
Artemisinin is an important frontline antimalarial . Fast, accurate detection of artemisinin in human serum is of importance in monitoring its clinical pharmaceutical effect. In this work, a strategy using microsensor array coupled with electrochemiluminescence (ECL) imaging technique was developed for detection of artemisinin. The microsensor array was constructed by integrating a patterned indium tin oxide glass plate with two perforated hydrophobic paper covers. By introducing the reactant of p-aminophenylboronic acid, luminol and artemisinin into the microsensor array, artemisinin would oxidize p-aminophenylboronic acid into p-aminophenol, a product which can efficiently inhibit the ECL of luminol. ECL signals decrease linearly with the increase of artemisinin. Based on the decreased ECL signal, artemisinin can be accurately detected. A good linearity ( r = 0.994) was observed for artemisinin detection. The detection sensitivity is 0.48 μM for artemisinin. The detection selectivity and stability were also investigated. Results show that the present method shows a good selectivity and stability towards artemisinin detection. To evaluate the applicability of the present strategy for detecting artemisinin in real samples, the artemisinin content in human serum and Artemisia annua samples were analyzed. Results demonstrated that the present strategy shows excellent selectivity with high sensitivity towards artemisinin detection in real samples.
研究领域:
分析化学
·
医学检测
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Yan Yang,Xiaomin Zhang,Xiaofen Wang,Xiaomei Zhao,Tianrui Ren,Feng Wang,Bo Yu
Artemisinin (ART) and its analogues, such as dihydroartesunate (DHA) and artesunate (ATS), are sesquiterpene lactones with anticancer activities. Transferrin (Tf) receptor is frequently overexpressed in cancer cells. In order to improve the delivery and the anticancer activity of ART and its analogues, adducts of Tf with ART, DHA or ATS were fabricated by simply combining ART, DHA or ATS with Tf. Increased antitumor effects of these adducts were observed on human liver hepatocellular carcinoma (HepG2) and lung adenocarcinoma (A549) cells. Meanwhile, only a low level of toxic effect was observed on normal human liver cells (HL-7702). Improved cellular uptake of ATS-Tf adduct compared to ATS alone was confirmed by HPLC analysis. UV–vis, fluorescence spectroscopy and docking study further confirmed the formation of the adducts with relatively high binding constants at neutral pH (7.4 × 10 4 , 4.2 × 10 5 and 3.4 × 10 5 M −1 , for ART-Tf, DHA-Tf and ATS-Tf, respectively, at pH 7.4). However, the adducts became less stable with reduced binding constants under an acidic condition (2.6 × 10 4 , 1.9 × 10 4 and 1.7 × 10 4 M −1 , for ART-Tf, DHA-Tf and ATS-Tf, respectively, at pH 5.5). A possible mechanism of the anticancer effect by these adducts was proposed. The short term and long term stability of ART-Tf in the presence of human serum albumin (HSA) was also studied. Our results showed that adducts of ART and its analogues with Tf, especially ATS-Tf and DHA-Tf, have significant anticancer effects to cancer cells, with minimal side effects on normal cells, therefore, are promising as potential novel anticancer agents.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AOAC INTERNATIONAL
·
2021
·Vol. 104
·期 4
·1206-1212
·
IF 1.913
You Cong,Yu Jun,Qin Guangjiong,Yang JinPeng,Yang Chunlei,Hu Guoyuan
BackgroundArtemisia hedinii is a well-known traditional Chinese medicine. It can be used to extract dihydroartemisinin (DHA).ObjectiveThe purpose of this study was to explore the optimal conditions for the homogenate extraction of DHA from A. hedinii and the antifungal activity of DHA.MethodsIn this study, single-factor experiments and the response surface method were used to determine the optimal extraction conditions of crude extract and DHA. The method of spore germination was used to study the antifungal activity of DHA on Alternaria alternata.ResultsThe optimal conditions were found as follows: ratio of liquid to material 22 mL/g; extraction time 60 s; and soaking time 34 min. Under these conditions, extraction yield of DHA was (1.76 ± 0.04%). When the concentrations of crude extract were 0.5 and 8 mg/mL, the spore germination inhibition rates of A. alternata were (17.00 ± 2.05%) and (92.56 ± 2.01%), which were 3.34 and 1.15 times that of the DHA standard, respectively.ConclusionsHomogenate extraction technology is a fast and efficient method for extracting DHA from A. hedinii. The crude extract has significant antifungal activity against A. alternata and is inexpensive, providing possible DHA usage in the prevention and treatment of plant pathogenic fungi.HighlightsThe optimum conditions of the extraction of DHA from A. hedinii by homogenate extraction were obtained. DHA has antifungal activity against A. alternata. Compared with pure DHA, the crude extract has stronger antifungal activity against A. alternata.
研究领域:
中药学
·
植物化学
·
药理学
✓ 已验证
DOI
PubMed
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
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Chuanxun Zhang,Bo Hu,Jiajia Ren,Wanqi Du,Minjia Meng
The selective separation and purification of artesunate (ARU) and artemisinin (ART) using zirconium-based metal–organic frameworks (MOF), especially UiO-66 MOF, are receiving increasing attention. In this study, tunable “hydrophobic” sites of thiol (–SH) were introduced to amino-functionalized MOFs (UiO-66-NH2) to fabricate a thiol-amino bifunctional UiO-66/polyvinylidene fluoride (PVDF)-blended membrane (S1-UiO/PVDF-DPIM) via the delayed-phase-inversion method for selective separation of ARU/ART. The adsorption results indicated that the modification of UiO-66-NH2 with thiol can indeed increase the ARU adsorption. The thiol-functional MOF (S1-UiO-66-NH2) was chosen as the optimal thiol-amino bifunctional MOF, as it possessed the maximum ARU adsorption capacity (111.14 mg g–1) and the highest selective-separation factor (α = 51.84). The ATR FT-IR dynamic spectrum disclosed the recognition mechanism, indicating that incorporating thiol groups into a hydrophilic MOF as hydrophobic sites can boost adsorption efficiency. Moreover, the static-selective permeation results showed that the S1-UiO/PVDF-DPIM preferentially transfers ARU when mixed with ART, even achieving complete ARU/ART separation. The most crucial aspect was the introduction of a hydrophobic core of –SH and new spontaneously formed disulfide bonds to S1-UiO/PVDF-DPIM, creating alternated hydrogen bonds and hydrophobic interactions. This work provides an alternative strategy to prepare hydrophobic–hydrophilic MOF-based membranes for the highly efficient and selective separation of complex analogue systems.
研究领域:
材料科学
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药物化学
·
分离技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AICHE JOURNAL
·
2022
·Vol. 68
·期 8
·e17711
·
IF 4.167
Yingying Cao,Xin Tan,Guoxiong Zhan,Qiongguang Li,Hui Wang,Zengxi Li
One of the challenges to obtain high-quality natural active substances is the selective separation of the target compound from its analogues. In this study, ionic liquids (ILs), with design flexibility, were proposed to separate artemisitene and artemisinin, typical examples of natural analogues. Based on COSMO-RS calculation, several ILs were selected to separate artemisitene/artemisinin by experiment. It was demonstrated that the aqueous solution of N -allyl- N,N,N -trimethylammonium chloride ([AA][Cl]) exhibited excellent capability for selective separation of the two compounds. Under the optimal conditions (40°C, 1 h), the separation selectivity of artemisitene/artemisinin could reach 12.23 when the initial impurity content was only 0.8 wt%. Spectroscopic analysis and molecular dynamics indicated that π – π complexation between artemisitene and [AA][Cl] plays a major role in this separation process. Moreover, the process of multistage cross-flow extraction was compared with counter-flow extraction, and the latter one exhibited advantages in energy consumption and product yield.
研究领域:
化学工程
·
天然产物化学
·
药物化学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Minjia Meng,Yi Li,Hui Peng,Binrong Li,Chuanxun Zhang,Jiajia Ren,Qingluola Ren,Yan Liu,Jianming Pan
The selective separation and purification of ART and ARE using molecularly imprinted membrane (MIM) has attracted considerable attention, but most of conventional blending MIM face low adsorption capacity and poor selectivity due to the blockage of imprinting sites. Herein, an alternative ART imprinted MnO 2 nanowires “coating” membrane (MINM) with hydrophilicity was fabricated by vacuum filtration of imprinted MnO 2 nanowires and graphene oxide nanosheets on PVDF membrane surface for selective ART separation. For the MINM, the imprinted MnO 2 nanowires coating offers more available exposed imprinting sites on the MINM surface compared to that of the blending MIM, while the introduction of graphene oxide improves the hydrophilicity of MINM, significantly reducing the non-specific absorption. Consequently, the MINM exhibits ultrahigh ART adsorption capacity and selectivity, with the ART adsorption amount of 335 mg g −1 at 5 min using dynamic cross-flow separation system, about 12.18 times higher than that of ARE (27.5 mg g −1 ), and the separation factor ( a ) value of 12.39. Moreover, the ATR FT-IR dynamic spectrum discloses the in-situ formation of H-bond between ART and MINM, playing a key role in the selective adsorption process. This work provides an alternative strategy to prepare “coating” MIM for high-efficient and selective separation of complex analogue systems.
研究领域:
材料科学
·
药物化学
·
分离技术
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Minjia Meng,Suao Wang,Jingyi Dai,Yi Li,Yonghai Feng,Yu Zhu,Hongbo Zhang,Yan Liu
In this work, a simple metal-organic framework (MOF) material, UiO-66-NH 2 , was prepared for the highly efficient separation of artemisinin (Art) and artesunate (Aru). Selective adsorption tests showed that UiO-66-NH 2 presented a much higher selectivity toward Aru than Art ( α Aru/Art = 40.74). The N 2 adsorption-desorption isotherm results of UiO-66-NH 2 indicated a suitable pore size to enable the free entry of Art and Aru. Contact angle analysis indicated that UiO-66-NH 2 is hydrophilic with the -NH 2 group, and can interact with the hydrophobic Aru through hydrogen bonding between the -NH 2 and -COOH groups, which is not possible with the hydrophobic Art. The selective adsorption of Aru onto UiO-66-NH 2 may be attributed to three factors: pore size, functional groups, and difference in hydrophobic/hydrophilic characteristics between the adsorbent and adsorbate. Molecularly imprinted polymers (MIPs) were prepared using Aru as a template for selective adsorption experiments to verify the excellent selectivity of UiO-66-NH 2 . The adsorption amount (65.24 mg g −1 ) and selectivity factor ( α Aru/Art = 40.74) of UiO-66-NH 2 toward Aru were significantly better than those of the MIPs (2.039 mg g −1 and 3.072, respectively). The binding capacity and better selectivity of UiO-66-NH 2 provide evidence supporting the potential of MOF adsorbents for the separation of various analogous molecules.
研究领域:
药学
·
材料科学
·
分离技术
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF ADHESION AND ADHESIVES
·
2023
·
IF 3.4
Yashuang Ding,Qiongfang Li,Wenya Tang,Yahui Pan,Rongrong Nie,Xiangfeng Meng
Objectives This study aims to investigate the potential effect of a primer containing Artemisinin (ART) or its derivative—dihydroartemisinin (DHA) on the dentin endogenous MMPs activity and resin bonding durability under etch-and-rinse mode. Materials and methods Molecular docking was applied for evaluating the potential interactions of MMP-2 and MMP-9 with ART and DHA. Then human third molars were randomly assigned to six groups, after etch-and-rinse treatment, pretreated with the primers containing 0.25, 0.5 mg/mL ART, 0.25, 0.5 mg/mL DHA and 2% chlorhexidine (CHX) for 2 min, respectively, while one untreated group was served as the control group. The endogenous MMPs activity of demineralized dentin was tested with in situ zymography test and zymographic assay. Following the etch-and-rinse bonding process with a universal resin bond , the specimens of the microtensile bond strength (μTBS) and nanoleakage were tested with or without 10,000 °C thermocycling and 6-month storage in artificial saliva at 37 °C. Results Molecular docking showed that ART and DHA combined with MMP-2 and MMP-9 through forming covalent bonds with the zinc ion of MMPs. Compared with the control group, the ART, DHA and CHX groups showed less endogenous MMPs activity, and the MMPs activity of 0.5 mg/mL DHA group had no significant difference from that of 2% CHX group. Ageing condition reduced the μTBS values dramatically and also aggravated the nanoleakage of all the groups, specifically, the control group showed lower μTBS value and a broader, thicker and more consecutive silver deposition than other groups. Conclusions The primer containing ART or DHA could preserve bond durability and slow down the nanoleakage of resin-dentin interface over time through inhibiting the endogenous MMPs activity.
研究领域:
牙科学
·
分子生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Wei He,Yawei Du,Chuncao Li,Ji Wang,Yang Wang,Con Dogovski,Rui Hu,Zhiyong Tao,Chen Yao,Xinsong Li
Artesunate (ARS) is the only artemisinin-based intravenous drug approved for treatment of malaria in the clinic. ARS is rapidly metabolized in vivo to short lived (∼30–45 min) but fast acting, dihydroartemisinin (DHA). The short half-life of DHA necessitates multiple dose administration to circumvent the risk of recrudescence and development of artemisinin resistance. In this work, we report a stable, safe and potent alternative artemisinin-based injectable nanocomplex consisting of dimeric artesunate-choline conjugate (dACC) micelles coated with hyaluronic acid (HA). Firstly, dACC was synthesized by one-step esterification of two artesunate molecules with 3-(dimethylamino)-1,2-propanediol followed by quaternization. After that, dACC was self-assembled into cationic nanomicelles and further coated with anionic small molecular weight HA. The HA-coated dACC nanocomplex (dACC/HA nanocomplex) has a narrow size distribution of about 30 nm. Hemolytic toxicity and cytotoxicity studies revealed a favorable bio-safety profile. Finally, in vitro and in vivo studies showed the dACC/HA nanocomplex possess superior safety and antimalarial efficacy compared to ARS. Taken together, the dACC/HA nanocomplex is a promising injectable alternative to the traditional clinically used artesunate.
研究领域:
药剂学
·
传染病学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 2.997
Liqing Chai,Rongrong Wang,Yan Wang,Wenju Guo,Ning Li,Hengtong Zuo,Yidan Wang,Danyu Duan,Guolian Ren,Bin Zheng,Ruili Wang,Shuqiu Zhang
Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio ( ER h ) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect. The induction capacities of ARTs to cytochrome P450 ( CYP450 ) in rats and human cells were evaluated as well. For ART, only the oral groups showed time-dependent PK. A fairly high ER h that obtained for ART was not sensitive to multiple oral doses. An increased elimination and CYP450 expression have also been found in the intestine. For DHA, though a significant CYP450 induction was observed, neither time-dependent PK nor changes in the first-pass effects was found. In conclusion, time-dependent PK of ART was mainly caused by the increased intestinal first-pass effect rather than hepatic first-pass effect or systemic metabolism. DHA was not involved in auto-induction elimination, thus showing no time-dependent PK.
研究领域:
药理学
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
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
·
水生生物学
✓ 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）