Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 18
·3840-3847
·
IF 4.726
Bo Wang,Limin Chen,Yingjuan Sun,Youliang Zhu,Zhaoyan Sun,Tiezhu An,Yuhua Li,Yuan Lin,Daping Fan,Qian Wang
Stable and monodisperse phenylboronic acid-functionalized nanoparticles (PBA-NPs) were fabricated using the 3-((acrylamido)methyl)phenylboronic acid homopolymer (PBAH) via the solvent displacement technique. The effect of operating parameters, including stirring time, initial polymer concentration and the proportion of methanol, on the self-assembly process was systematically investigated. The diameters of PBA-NPs were increased by increasing the initial PBAH concentration and the proportion of methanol. Likewise, there was a linear dependence between the size of self-assembled nanoparticles and the polymer concentration. Moreover, the dissipative particle dynamics (DPD) simulation technique was used to investigate the mechanism of self-assembly behavior of the PBAH, which indicated that the interior of PBA-NPs was hydrophobic and compact, and boronic acid groups were displayed on both the exterior and interior of PBA-NPs. The resulting PBA-NPs could successfully encapsulate emodin through PBA–diol interaction and the encapsulation efficiency (EE%) and drug loading content (DLC%) of drug-loaded PBA-NPs were 78% and 2.1%, respectively. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from 7.4 to 5.0 could trigger the disassociation of the boronate ester bonds, which could accelerate the drug release from PBA–emodin-NPs. Besides, PBA–emodin-NPs showed a much higher cytotoxicity to HepG2 cells (cancer cells) than MC-3T3-E1 cells (normal cells). These results imply that PBA-NPs would be a promising scaffold for the delivery of polyphenolic drugs.
研究领域:
药剂学
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纳米医学
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生物材料
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
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2021
·
IF 3.77
O.Yu. Selyutina,P.A. Kononova,V.E. Koshman,E.A. Shelepova,M. Gholam Azad,R. Afroz,M. Dharmasivam,Paul V. Bernhardt,N.E. Polyakov,D.R. Richardson
Background Iron (Fe)-induced oxidative stress leads to reactive oxygen species that damage biomembranes, with this mechanism being involved in the activity of some anti-cancer chemotherapeutics. Methods Herein, we compared the effect of the ligand, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), or the potential ligand, Emodin, on Fe-catalyzed lipid peroxidation in cell membrane models (micelles and bicelles). These studies were performed in the presence of hydrogen peroxide (H 2 O 2 ) and the absence or presence of ascorbate. Results In the absence of ascorbate, Fe(II)/Emodin mixtures incubated with H 2 O 2 demonstrated slight pro-oxidant properties on micelles versus Fe(II) alone, while the Fe(III)-Dp44mT complex exhibited marked antioxidant properties. Examining more physiologically relevant phospholipid-containing bicelles, the Fe(II)- and Fe(III)-Dp44mT complexes demonstrated antioxidant activity without ascorbate. Upon adding ascorbate, there was a significant increase in the peroxidation of micelles and bicelles in the presence of unchelated Fe(II) and H 2 O 2 . The addition of ascorbate to Fe(III)-Dp44mT substantially increased the peroxidation of micelles and bicelles, with the Fe(III)-Dp44mT complex being reduced by ascorbate to the Fe(II) state, explaining the increased reactivity. Electron paramagnetic resonance spectroscopy demonstrated ascorbyl radical anion generation after mixing ascorbate and Emodin, with signal intensity being enhanced by H 2 O 2 . This finding suggested Emodin semiquinone radical formation that could play a role in its reactivity via ascorbate-driven redox cycling. Examining cultured melanoma cells in vitro , ascorbate at pharmacological levels enhanced the anti-proliferative activity of Dp44mT and Emodin. Conclusions and general significance Ascorbate-driven redox cycling of Dp44mT and Emodin promotes their anti-proliferative activity.
研究领域:
生物化学
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药理学
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肿瘤学
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PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2019
·Vol. 22
·期 2
·113-122
·
IF 1.503
Zhang Xin-guo,Ma Guo-Yan,Kou Fei,Liu Wen-Jie,Sun Qiao-Yun,Guo Guang-Jun,Ma Xiao-Di,Guo Si-Jia,Jian-Ning Zhu
Background: Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy
to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents. Objective: In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors. Results: Extracts
from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica
possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by
1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity
against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin. Conclusion: Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.
研究领域:
药理学
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肿瘤学
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植物化学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 22
·13738
·
IF 6.208
Guorong Cheng,Zhiqiang Liu,Zhong Zheng,Fengrui Song,Xiaoyu Zhuang,Shu Liu
Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.Keywords:aloe emodin (AE);emodin (EMD);cell metabolomics;breast cancer;metastasis
研究领域:
肿瘤学
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药理学
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代谢组学
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PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2020
·
IF 3.184
Yulian Chen,Tao Zhang,Lili Wu,Yilin Huang,Zhihao Mao,Zhikun Zhan,Weizhong Chen,Fahong Dai,Wenyu Cao,Yong Cao,Shuwen Liu,Zheng Cai,Lan Tang
Emodin is the main toxic component in Chinese medicinal herbs such as rhubarb. Our previous studies demonstrated that genetic polymorphisms of UDP-glucuronosyltransferase 2B7 (UGT2B7) had an effect on the glucuronidation and detoxification of emodin. This study aimed to reveal the transcriptional regulation mechanism of UGT2B7 on emodin glucuronidation and its effect on toxicity. Emodin glucuronic activity and genome and transcriptome data were obtained from 36 clinical human kidney tissues. The genome-wide association studies (GWAS) identified that four single nucleotide polymorphisms (SNPs) (rs6093966, rs2868094, rs2071197, and rs6073433), which were located on the hepatocyte nuclear factor 4α (HNF4A) gene, were significantly associated with the emodin glucuronidation (p < 0.05). Notably, rs2071197 was significantly associated with the gene expression of HNF4A and UGT2B7 and the glucuronidation of emodin. The gene expression of HNF4A showed a high correlation with UGT2B7 (R2 = 0.721, p = 5.83 × 10–11). The luciferase activity was increased 7.68-fold in 293T cells and 2.03-fold in HepG2 cells, confirming a significant transcriptional activation of UGT2B7 promoter by HNF4A. The knockdown of HNF4A in HepG2 cells (36.6%) led to a significant decrease of UGT2B7 (19.8%) and higher cytotoxicity (p < 0.05). The overexpression of HNF4A in HepG2 cells (31.2%) led to a significant increase of UGT2B7 (24.4%) and improved cell viability (p < 0.05). Besides, HNF4A and UGT2B7 were both decreased in HepG2 cells and rats after treatment with emodin. In conclusion, emodin used long term or in high doses could inhibit the expression of HNF4A, thereby reducing the expression of UGT2B7 and causing hepatotoxicity.
研究领域:
药理学
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遗传学
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毒理学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 10
·5444
·
IF 4.9
Gelana Urgesa,Liushen Lu,Jinwei Gao,Lichun Guo,Ting Qin,Bo Liu,Jun Xie,Bingwen Xi
Aeromonas hydrophilacan be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibitingA. hydrophilais urgently required. Emodin, a naturally occurring anthraquinone compound, was exploited as a photo-antimicrobial agent againstA. hydrophila. At the minimum inhibitory concentration of emodin (256 mg/L) to inactivateA. hydrophiliain 30 min, an 11.32% survival rate was observed under 45 W white compact fluorescent light irradiation. In addition, the antibacterial activity under natural sunlight (0.78%) indicated its potential for practical application. Morphological observations demonstrated that the cell walls and membranes ofA. hydrophilawere susceptible to damage by emodin when exposed to light irradiation. More importantly, the photoinactivation ofA. hydrophilawas predominantly attributed to the hydroxyl radicals and superoxide radicals produced by emodin, according to the trapping experiment and electron spin resonance spectroscopy. Finally, a light-dependent reactive oxygen species punching mechanism of emodin to photoinactivateA. hydrophilawas proposed. This study highlights the potential use of emodin in sunlight-mediated applications for bacterial control, thereby providing new possibilities for the use of Chinese herbal medicine in aquatic diseases prevention.
研究领域:
微生物学
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环境科学
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药学
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水产养殖
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Dongpeng Wang,Jufeng Duan,Xiao-Jing Chen,Kaiqi Liu,Yingying Guo,Run Shi,Sha Li,Ming Liu,Lijun Zhao,Bei Li,Hongtao Liu,Minglun Li,Yibin Feng,Hongliang Li,Xuanbin Wang
Ethnopharmacological relevance Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro . However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo . Aim of the study In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. Materials and methods Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O- β -D-glycoside (EMG), physcion-1-O- β -D-glycoside (PHG) and chrysophanol-8-O- β -D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. Results The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, C max (239.90 ± 146.71 vs . 898.46 ± 291.62, P < 0.001), T max (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC 0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC 0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of V d (380.75 ± 217.74 vs . 11.75 ± 7.35, P < 0.001), T 1/2 (10.81 ± 1.99 vs . 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs . 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs . 43.29 ± 4.16 and 26.72 ± 4.03 vs . 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. Conclusion In conclusion, compared with treatment of EM alone, the AUC 0-t value of EM in HSWE was decreased with different ways in rats. PH shortened T max , and increased V d and CL. While AE prolonged T 1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4′-tetrahydroxystilbene-2-O- β -D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.
研究领域:
中药学
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药理学
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生物化学
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2024
·
IF 7
Jiali Wu,Yaokun Pang,Dan Liu,Jianxia Sun,Weibin Bai
Aloe-emodin (AE) is a natural compound with photodynamic properties. The aim of this study was to investigate the inhibitory effect of AE-mediated photodynamic inactivation (PDI) on Staphylococcus aureus ( S. aureus ). The bacteriostatic efficiency under different photodynamic conditions and photosensitizing mechanism was studied in detail. The results showed that AE-mediated PDI exhibited a typical concentration and time-dependent characteristics. In terms of bactericidal mechanism, disruption of membrane integrity and increase of cell membrane permeability was observed. Type II reaction was assumed as the main photochemical reaction involved in AE-mediated PDI as evidenced by the action of different ROS quenching agents. Furthermore, AE-mediated PDI decreased the bacterial survival in freshly squeezed apple juice and maintained its quality. The combination of blue light and AE enlarged the application of AE as an effective natural photosensitizer suitable for a food system.
研究领域:
微生物学
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食品科学
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药学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2018
·
IF 3.432
Li-Long Jiang,Yan Jiang,Dong-Sheng Zhao,Ya-Xi Fan,Qiong Yu,Ping Li,Hui-Jun Li
1,3,8-Trihydroxy-6-methylanthraquinone (emodin), a widely existing natural product in herbal medicines, has been reported to be hepatotoxic, but the exact underlying mechanism is still not fully understood. The objective of the present study was to evaluate the role of CYP3A and glutathione (GSH) in emodin-induced liver injury. Primary human hepatocytes were exposed to emodin with and without addition of CYP3A inducer/inhibitor and GSH synthesis inhibitor. It was found that emodin-mediated cytotoxicity increased when CYP3A was activated and GSH was depleted. Hepatotoxicity induced by emodin in rats by activation/inhibition of CYP3A and depletion of GSH was further investigated. Administration of emodin in combination with l-buthionine sulfoximine (BSO) or dexamethasone (DEX) resulted in aggravated liver injury, whereas pretreatment with ketoconazole (KTZ) suppressed the side effects caused by emodin. In addition, plasma exposure of emodin and its glucuronide metabolite were measured by ultraperformance liquid chromatography triple quadrupole mass spectrometry. Emodin and its glucuronide were lower in BSO-, DEX-, and KTZ-co-treated rats compared with those administered with emodin alone. In conclusion, these mentioned results suggested that CYP3A induction and GSH depletion might be involved in hepatotoxicity induced by emodin. This study may help to understand the risk factors and the mechanism of hepatotoxicity of emodin in humans.
研究领域:
药理学
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毒理学
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药学
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2019
·
IF 3.274
Ruihong Li,Wei Li,Yutong You,Xiucai Guo,Ying Peng,Jiang Zheng
Aloe-emodin (AE) is a major anthraquinone ingredient of numerous traditional Chinese medicines with a variety of beneficial biological activities in vitro. Previous studies suggested that AE possessed cytotoxicity and genotoxicity. Nevertheless, the mechanisms of the toxic action of AE have not yet been fully clarified. The present study aimed at characterization of metabolic pathways of AE to better understand the mechanisms of AE-induced cytotoxicity. An AE-derived glutathione conjugate (AE-GSH) was observed in rat liver cytosol incubations containing AE and GSH, along with 3′-phosphoadenosine-5′-phosphosulfate (PAPS). Similar incubation fortified with N-acetylcysteine (NAC) in place of GSH offered an AE-NAC conjugate corresponding to the GSH conjugate. The formation of the two conjugates was found to require PAPS. The two conjugates were respectively detected in bile and urine of rats given AE. Sulfotransferase (SULT) inhibitor pentachlorophenol (PCP) suppressed the production of the observed AE-GSH/NAC conjugates in vivo, which suggested that SULTs participated in the process of the metabolic activation of AE. The presence of PCP attenuated cell susceptibility to AE-induced cytotoxicity. The present study illustrated potential association of sulfation-mediated bioactivation of AE with its cytotoxicity.
研究领域:
药理学
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毒理学
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生物化学
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Xu Wang,Zifang Ding,Kaiqi Ma,Chen Sun,Xiaojiao Zheng,Yutong You,Shiyu Zhang,Ying Peng,Jiang Zheng
Emodin (EMD) is a major ingredient of Polygonum multiflorum Thunb. (PMT), which has shown adverse liver reactions. Despite multiple pharmacological activities, EMD is reported to show various toxicities. Our early study demonstrated the reactivity of EMD to glutathione. This study aimed to determine the covalent interaction of hepatic protein with EMD and the correlation of the protein modification with hepatotoxicity induced by EMD. EMD-derived protein adduction was detected in an incubation mixture containing mouse liver homogenates and EMD. Such protein adduction was also observed in hepatic protein obtained from mice exposed to EMD. The protein covalent binding occurred in time- and dose-dependent manners. Pre-treatment of l-buthionine-sulfoximine significantly potentiated EMD-induced adduction and hepatotoxicity caused by EMD and lipopolysaccharide co-treatment. As expected, EMD-derived protein modification was observed in mouse primary hepatocytes treated with EMD. The increase in EMD exposure concentration intensified EMD-derived protein adduction and increased EMD-induced cell death. The susceptibility of hepatocytes to EMD cytotoxicity and the intensity of EMD-induced protein adduction were attenuated by the co-treatment of hepatocytes with N-acetyl cysteine. A good association of protein modification with hepatotoxicity induced by EMD was illustrated, which facilitates the understanding of the mechanism of hepatotoxicity induced by EMD.
研究领域:
药理学
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毒理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Bionic Engineering
·
2022
·Vol. 20
·期 3
·1060-1071
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IF 2.995
Pan Yiwen,He Mu,Chen Shaoqing,Meng Yanyan,Wang Cheli,Ni Xinye
Biological scaffolds have been the focus of bone tissue engineering research in recent years. In this paper, emodin (EM), macromolecular compound polycaprolactone (PCL), and hydroxyapatite (HA) were used as raw materials to prepare EM/PCL/HA fibers containing different EM ratios by electrospinning, and the properties and osteogenic efficacy of EM/PCL/HA were studied. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy were used to characterize the structures of HA and the electrospun fibers. Results showed that HA has high crystallinity and loose porous structure, and the electrospun fibers have a smooth and flat surface. In vitro release results showed that EM was slowly released from EM/PCL/HA within 216 h. Cell proliferation assay in mouse embryonic osteoblast precursor cells (MC3T3-E1) exhibited that 5% EM/PCL/HA had the best effect on promoting cell proliferation. Alkaline phosphatase (ALP) and mineralized nodules staining results also showed that 5% EM/PCL/HA had the best effect on promoting osteogenic differentiation. qRT-PCR results showed that the mRNA expression level of osteoblast differentiation markers, namely, bone morphogenetic protein (BMP)-2, BMP-9, and osteocalcin were significantly upregulated by 5% EM/PCL/HA treatment. These results indicate that EM/PCL/HA is a potential osteogenic material, which can provide a reference for the development of bone injury repair materials.
研究领域:
材料科学
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生物医学工程
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组织工程
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生物材料
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）