INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2013
·
IF 3.458
Jingyi Shen,Dianrui Zhang,Zhongxi Zhao,Lejiao Jia,Dandan Zheng,Guangpu Liu,Leilei Hao,Qiang Zhang,Xiaona Tian,Caiyun Li,Hejian Guo
Oridonin (ORI), a diterpenoid compound with promising antitumor activity , was proved to possess potent antileukemia efficacies in vitro and in vivo recently. However, the development and application of ORI was limited by its poor solubility and rapid plasma clearance. The purpose of this study was to solve these problems. PEGylated oridonin linked with succinic acid (SA) as spacer moiety (PEG-SA-ORI conjugate) was synthesized. mPEG amines with four specifications of molecular weight (MW) were utilized. All polymeric conjugates showed satisfactory aqueous solubility and in vitro studies implied that the drug solubility and release features of conjugates were relevant to PEGs. The drug solubility increased more when the MW of PEG was lower, while more significant sustained-release effect was shown with higher PEG MW. Moreover, the release behaviors of conjugates showed a pH-sensitive property. In vivo pharmacokinetic studies demonstrated that the elimination half-life was prolonged in comparison with ORI solution. PEGylation could be a promising method to obtain better efficacy in the field of drug delivery system .
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INTERNATIONAL JOURNAL OF FOOD PROPERTIES
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2016
·
IF 1.586
Kechan Lei,Wanxing Wei,Sheng Liu,Min Zhou,Xiaoxia Lin,Xun Cao
Antioxidant activities of the extract containing anthocyanins from fruit of Sageretia theezans Brongn were investigated in this work. The fruit of Sageretia theezans Brongn was treated with 0.001 mol·L–1 HCl in a solid (g): liquid (mL) ratio 1:10 to give extract. Total anthocyanins content was 253.10 ± 2.31 mg in 100 g fruit. The anthocyanins in extract were determined as cyanidin-3-sophorose-5-glucoside (Cy-3-Sp-5-Glu), petunidin-3-(6′-malonyl)-glucoside (Pt-3-(6’-Mal)-Glu), malvinidin-3-glucosid (Mv-3-Glu), and peonidin-3-(6′-malonyl)-glucoside (Pn-3-(6’-Mal)Glu) in 0.38, 22.57, 44.32, and 30.86%, respectively, by high performance liquid chromatography-mass spectrometry method. Antioxidant activities of the anthocyanins in extract were evaluated by methods of ferric reducing antioxidant power, hydroxyl radical scavenging assay, and superoxide radical scavenging assay. The anthocyanins in extract exhibited obvious antioxidative activities. These results suggested that the fruit of Sageretia theezans Brongn could be considered as a good source of natural antioxidants.
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MACROMOLECULES
·
2016
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IF 5.554
Xu Li,Bolin Li,Xiaodong Zhang,Chengcheng Li,Zhirui Guo,Dongshan Zhou,Xiaolin Lu
Understanding the interfacial molecular structures of antifouling polymers in solutions is extremely important in research and applications related to chemistry, biology, and medicine. However, it is generally challenging to probe such buried solid/liquid interfaces in situ. We herein report a molecular-level study on detecting the interfacial molecular structures of an antifouling hydrogel material, poly(2-hydroxyethyl methacrylate) (PHEMA), in contact with water and bovine serum albumin (BSA) solution in situ using sum frequency generation (SFG) vibrational spectroscopy. To compare to and validate our in situ experiments, molecular-level structures of the substrate/PHEMA interface before and after water exposure were also detected. The detected strong O–H vibrational signals from water and hydroxyethyl and carbonyl vibrational signals from PHEMA prove that the PHEMA surface hydration was attributed to the interaction between water and PHEMA side hydrophilic groups. SFG experimental results verify that the adsorbed BSA molecules at the PHEMA/solution interface were disorderly arranged, supported by data from the laser scanning confocal microscopic (LSCM) experiment. This indicates the weak interaction between the BSA molecules and PHEMA surface. This direct detection of the surface hydrated structures of PHEMA sheds light on understanding the interfacial properties of antifouling materials in aqueous environments. The capability reported here to probe the PHEMA/solution interface and the hidden substrate/PHEMA interface after water exposure can be applied to investigate a broad range of interfaces of antifouling materials.
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JOURNAL OF ETHNOPHARMACOLOGY
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2016
·
IF 3.055
Lifeng Niu,Lina Ding,Chunyun Lu,Feifei Zuo,Ke Yao,Shaobo Xu,Wen Li,Donghua Yang,Xia Xu
Ethnopharmacological relevance Flavokawain A, the major chalcone in kava extracts , was served as beverages for informal social occasions and traditional ceremonials in most South Pacific islands. It exhibited strong antiproliferative and apoptotic effects against human prostate and urinary bladder cancer cells. Aim of the study The current study was purposed to investigate the interaction between Flavokawain A and Cytochrome P450 , including the inhibitory effects of Flavokawain A on predominant CYP450 isotypes and further clarified the inhibitory mechanism of FKA on CYP450 enzymes. Besides, study about identifying the key CYP450 isotypes responsible for the metabolism of FKA was also performed. Materials and methods In this study, probe-based assays with rat liver microsome system were used to characterize the inhibitory effects of FKA. Molecular docking study was performed to further explore the binding site of FKA on CYP450 isoforms. In addition, chemical inhibition experiments using specific inhibitors (a-naphthoflavone, quinidine , sulfamethoxazde, ketoconazole, omeprazole) were performed to clarify the individual CYP450 isoform that are responsible for the metabolism of FKA. Results FKA showed significant inhibition on CYP1A2 , CYP2D1 , CYP2C6 and CYP3A2 activities with IC 50 values of 102.23, 20.39, 69.95, 60.22 μmol/L, respectively. The inhibition model was competitive, mixed-inhibition, uncompetitive, and noncompetitive for CYP1A2, CYP2D1, CYP2C6 and CYP3A2 enzymes. Molecular docking study indicated the ligand-binding conformation of FKA in the active site of CYP450 isoforms. The chemical inhibition experiments showed that the metabolic clearance rate of Flavokawain A decreased to 19.84%, 50.38%, and 67.02% of the control in the presence of ketoconazole, sulfamethoxazde and a-naphthoflavone. Conclusion The study showed that Flavokawain A has varying inhibitory effect on CYP450 enzymes and CYP3A2 was the principal CYP isoform contributing to the metabolism of Flavokawain A. Besides, CYP2C6 and CYP1A2 isoforms also play important roles in the metabolism of FKA. Our results provided a basis for better understanding the biotransformation of FKA and prediction of drug-drug interaction of FKA.
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Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Zhang Chong,Cao Songxiao,Jin Yazhong,Ju Lijun,Chen Qiang,Xing Qiaojuan,Qi Hongyan
To better understand the function role of the melon CmLOX18 gene in the biosynthesis of C6 volatiles during fruit ripening, we biochemically characterized CmLOX18 and identified its subcellular localization in transgenic tomato plants. Heterologous expression in yeast cells showed that the molecular weight of the CmLOX18 protein was identical to that predicted, and that this enzyme possesseed lipoxygenase activity. Linoleic acid was demonstrated to be the preferred substrate for the purified recombinant CmLOX18 protein, which exhibited optimal catalytic activity at pH 4.5 and 30 °C. Chromatogram analysis of the reaction product indicated that the CmLOX18 protein exhibited positional specificity, as evidenced by its release of only a C-13 oxidized product. Subcellular localization analysis by transient expression in Arabidopsis protoplasts showed that CmLOX18 was localized to non-chloroplast organelles. When the CmLOX18 gene was transgenically expressed in tomato via Agrobacterium tumefaciens -mediated transformation, it was shown to enhance expression levels of the tomato hydroperoxide lyase gene LeHPL , whereas the expression levels of six TomLox genes were little changed. Furthermore, transgenic tomato fruits exhibited increases in the content of the C6 volatiles, namely hexanal, (Z)-3-hexanal, and (Z)-3-hexen-1-ol, indicating that CmLOX18 probably plays an important role in the synthesis of C6 compounds in fruits.
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BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Qianqian Qi,Zhanyu Zhang,Dun Wang
The lack of targeting and poor solubility of anti-tumor drugs are two major limitations to the outcome of tumor therapy. To address the inherent drawbacks, we designed a novel prodrug of paclitaxel (PTX), HP-PTX. This HP-PTX prodrug contains a PEGylated heptamethylene cyanine dye (PEG-IR808–1) that was conjugated to PTX via a redox-sensitive disulfide bond. The moiety of IR808–1 acts as a tumor-targeting ligand, enabling HP-PTX not only to target tumor cells, but also to localize to mitochondria and generate ROS under 808 nm laser irradiation to wound cellular mitochondria thus exerting cytotoxic effect. Meanwhile, in vitro cellular uptake assays showed that HP-PTX possesses MCF-7 cell tumor targeting specificity which was attributed to the preferential uptake of heptamethine cyanine dye mediated by the overexpressed organic anion-transporting polypeptides (OATP) on MCF-7 cell membrane. Near-infrared in vivo imaging showed that incorporation of polyethylene glycol effectively prolonged prodrug's half-life in vivo. In addition, in vivo experiments showed that with combinational therapy strategy HP-PTX was able to kill cancer cells with high efficiency (69.52 %) without notable toxic side effects compared to PTX. These results are evidence of the potential of the tumor-targeting prodrug HP-PTX for the treatment of breast cancer.
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CHEMICAL RESEARCH IN TOXICOLOGY
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2024
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IF 3.7
Ximei Li,Lihua Xin,Lan Yang,Yi Yang,Wei Li,Mingyu Zhang,Yufen Liao,Chen Sun,Weiwei Li,Ying Peng,Jiang Zheng
Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.
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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2024
·Vol. 40
·期 2
·279-286
·
IF 3.1
Dou Renju,Wang Qin,Ren Xiaoyan,Lu Lehui
Here we employ in-situ UV-Vis spectroscopy to monitor the sulfur redox reaction with oxygen-containing molecules as an additive, for example, biphenyl-4,4′-dicarboxylic acid (BDC). Furthermore, Raman spectrum, electron paramagnetic resonance (EPR), and electrospray ionization-mass spectrometry (ESI-MS) measurements reveal that the formation of BDC-S
•‒ 3
complexes can establish the long-term stability of polysulfide radicals, change the kinetics of sulfur redox reaction, and then generate decent capacity retention and rate capability. According to the density functional theory (DFT) analysis, S
•‒ 3
radicals are the underlying product of S
2‒ 6
cleavage, owing to the decreased chemical energy and the increased stability of S
•‒ 3
radicals through Lewis acid-base interaction. The assembled Li-S batteries with BDC additive deliver a high reversible capacity of 420 mA·h·g −1 over 200 cycles with over 98% Coulombic efficiency, under the current density of 0.2 C.
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Photonics Research
·
2025
·Vol. 13
·期 3
·561-571
·
IF 7.2
Tiansheng Huang,Tiansheng Huang,Tongyu Wu,Tongyu Wu,Qi Fang,Qi Fang,Guangzheng Luo,Guangzheng Luo,Li-Peng Sun,Li-Peng Sun,Bai-Ou Guan,Bai-Ou Guan
Semiconductor metal oxides with narrow bandgap have emerged as a promising platform for photoelectrochemical reactions, yet their photoelectron-induced photocorrosion effect has been a limitation for their wider applications. Understanding the conversion processes concomitant with photoelectrochemical reaction at the electrode–electrolyte interface plays a crucial role in revealing the corrosion mechanisms and advancing the development of efficient photocathodes. However, accurately and in situ tracking these dynamic chemical events remains a great challenge due to the fact that reaction processes occur at nanoscale interfaces. Here, we track the electrochemical growth and conversion of copper nanostructures at interface by the evanescent field of the surface plasmon wave by using a gold-coated optical fiber as an electrochemical electrode and light sensing probe. The results exhibit correlation between redox processes of copper species and plasmonic resonances. Furthermore, in situ fiber-optic detection reveals the photocorrosion dynamics under photoelectrochemical reaction, including photoelectron-induced self-reduction of copper oxide and self-oxidation of cuprous oxide. These demonstrations facilitate not only the diagnosis for the health condition of photocathode nanomaterial, but also the understanding of the underlying reaction mechanism, and thus are potentially crucial for advancing the development of highly efficient photocathodes in future energy applications.
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ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Yucui Shen,Ye Feng,Shengjie Liang,Chunyong Liang,Baoe Li,Donghui Wang,Jianwei Sun
Developing a microenvironment-responsive drug delivery system (DDS) for the gastrointestinal system is of great interest to enhance drug efficiency and minimize side effects. Unfortunately, the rapid-flowing digestive juice in the gastrointestinal tract and the continuous contraction and peristalsis of the gastrointestinal tract muscle accelerate the elimination of drug carriers. In this study, a boric hydroxyl-modified mesoporous Mg(OH)2 drug carrier is prepared to prolong the drug retention time. Results show that the newly designed DDS presents high biocompatibility and can immediately turn the free polyhydric alcohol molecules into a gelation form. The in situ-formed gelation network presents high viscosity and can prevent the drug carriers from being washed away by the digestive juice in the gastrointestinal tract.
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GREEN CHEMISTRY
·
2017
·Vol. 20
·期 1
·188-196
·
IF 9.125
Lin Tao,Mingmei Zhong,Jian Chen,Sanjeevi Jayakumar,Lina Liu,He Li,Qihua Yang
An efficient heterogeneous catalytic system for hydroformylation of long-chain alkenes is highly desirable for both academy and industry. In this study, an IL-in-oil Pickering emulsion system was employed for heterogeneous hydroformylation of 1-dodecene with Rh-sulfoxantphos as the catalyst and surface modified dendritic mesoporous silica nanospheres (DMSN) as the stabilizer. The IL-in-oil Pickering emulsion system outperformed IL-oil biphase, water-in-oil Pickering emulsion and IL-oil micelle system under similar reaction conditions to afford n/b ratio of 98 : 2, chemoselectivity of 94% and TOF of 413 h−1, among the highest ever reported for IL-oil biphase hydroformylation of long-chain alkenes. The high efficiency of IL-in-oil Pickering emulsion was primarily attributed to the increased interface area and unique properties of ILs. Studies also revealed that solid stabilizers with large and open pore channels could greatly increase the reaction rate of Pickering emulsion systems by accelerating the diffusion rate. The recyclable IL-in-oil Pickering emulsion is promising not only for hydroformylation of long-chain alkenes but also for catalytic reactions with immiscible liquids.
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PHYTOMEDICINE
·
2024
·
IF 6.7
Dihao Xie,Simin Zhong,Meixue Luo,Jiahao Xu,Ruoyan Zheng,Jiading Luo,Yiting Wang,Yongxing Guo,Lianxia Guo,Baojian Wu,Danyi Lu
Background Aristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored. Methods We initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and Per2-dLuc / Bmal1-dLuc reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of Bmal1 , as well as mice subjected to experimental jetlag, were utilized. Results Our findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene Bmal1 significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of Bmal1 ) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC). Conclusion Collectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN.
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