JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Wenxin Li,Shuji Chen,Xu Hong,Mengke Fang,Wansong Zong,Xiaokang Li,Jing Wang
As typical disinfection byproducts, monohaloacetic acids (monoHAAs) were reported to be cytotoxic and genotoxic with the order of iodoacetic acid (IAA) > bromoacetic acid (BAA) ≫ chloroacetic acid (CAA). However, it remains unknown for the toxicity of monoHAAs to biomacromolecules and the detailed molecular mechanisms. Consequently, the structural and functional responses of bovine serum albumin (BSA) to three monoHAAs (CAA, BAA and IAA) were compared by investigating their interactions using multi-spectroscopic methods, esterase-like activity assays and molecular docking simulations. Results found that monoHAAs stimulated the esterase-like activity of BSA to different levels with the order of CAA > IAA > BAA. The binding of monoHAAs affected the secondary structures, peptide skeleton and aggregation state of BSA. The interactions of BSA with CAA, BAA and IAA are dominated by van der Waals forces and hydrogen bonds, hydrophobic forces and electrostatic forces, respectively. The binding of CAA directly interferes the key residues Arg 254 and Tyr 147 to the activity but BAA and IAA do not. BAA and IAA interacted with Tyr residues by static and dynamic quenching, respectively. The binding constant suggested a relatively weak binding affinity for the interaction of BSA with BAA and with IAA. While CAA barely changed the fluorescence of BSA with the increase of exposure concentrations. Accordingly, this study provides a comprehensive view on the molecular toxicity of monoHAAs interacting with BSA.
✓ 已验证
产品关联
DOI
高影响因子
Drug Delivery and Translational Research
·
2023
·
IF 5.4
Jiao Xinyi,Peng Xingru,Jin Xin,Liu Ning,Yu Yang,Liu Rui,Li Zheng
The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10 −5 mol/m 3 and 6.37×10 −6 mol/m 3 . In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations. Graphical Abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Meiqing Zhu,Xiaohui Pang,Jie Wan,Xiaoping Xu,Xueyu Wei,Rimao Hua,Xiaoying Zhang,Yi Wang,Xiaofan Yang
Sulfonamide antibiotics (SAs) are widely used in medicine, animal husbandry and aquaculture, and excessive intake of SAs may pose potential toxicity to organisms. The toxicological mechanisms of two classical SAs, sulfamerazine (SMR) and sulfamethoxazole (SMT), were investigated by molecular docking, DFT and multi-spectroscopic techniques using HSA and BSA as model proteins. The quenching of HSA/BSA endogenous fluorescence by SMR was higher than that by SMT due to the stronger binding effect of the pyrimidine ring on HSA/BSA compared to the oxazole ring, and that result was consistent with that predicted by DFT calculations. Thermodynamic parameters show that the binding of SAs to HSA/BSA is an exothermic process that proceeds spontaneously (ΔG < 0). Marker competition experiments illustrate that the binding site of SMR/SMT on serum albumin is located in subdomain IIIA. The combination of SAs and HSA/BSA is mainly realized by hydrogen bond and hydrophobic interaction, and the concept is also supported by molecular modeling. The reduced α -helix content of HSA/BSA induced by SMR/SMT indicates a greater stretching of the protein α -helix structure of the SMR/SMT-HSA/BSA. The results could provide useful toxicological information on the hazards of SAs in response to growing concern that SAs may pose a toxic threat to organisms.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2020
·
IF 5.065
Hengjun Rao,Wei Qi,Rongxin Su,Zhimin He,Xin Peng
Rhodamine B (RB), an important congeneric form of rhodamine dyes, is widely used as a colorant and tracing agent, and recent studies have shown that it is potentially harmful to wildlife and human health. To assess the toxicity of RB at the molecular level, the interaction between human serum albumin (HSA) and RB was investigated using NMR, multispectroscopic methods in combination with computational approaches. The data of NMR indicated that RB indeed bound to HSA, in which the benzene rings were spatially close to the binding site of HSA. The fluorescence results showed that RB had a moderate binding affinity to HSA and strongly quenched the intrinsic fluorescence of HSA through a static quenching mechanism. Analysis of thermodynamic parameters and the effect of ionic strength revealed that electrostatic , hydrophobic and hydrogen bond interactions played an important role in the complex formation. And the main binding region of RB was located near site I of HSA. Furthermore, the microenvironment and conformation of HSA were changed in the presence of RB, which was confirmed by the results obtained from CD, FT-IR, and synchronous fluorescence. Finally, the optimal binding mode of RB to HSA and the stability of HSA-RB complex were studied through molecular modeling methods. In short, this work would provide significant insights for understanding the transport, distribution and toxicity effect of RB when it spread in human body.
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Shufen Wu,Xiaochan Wang,Yuxin Bao,Chuanying Zhang,Huanhuan Liu,Zhenjing Li,Mianhua Chen,Changlu Wang,Qingbin Guo,Xin Peng
Monascin (MS) is a yellow lipid-soluble azaphilonoid pigment identified from Monascus -fermented products with promising biological activities. This work studied interactions between MS and bovine serum albumin (BSA) as well as their influences on the antioxidant activity of MS. Experimental results demonstrated that the fluorescence emission of BSA was quenched by MS via static quenching mechanism and the formed BSA-MS complex was mainly maintained by hydrophobic and hydrogen bond interactions. Meanwhile, the probable binding pocket of MS located near site I of BSA and the corresponding conformational and structural alterations of BSA were determined. Furthermore, the molecular modeling approach was performed to understand the visual representation of binding mode between BSA and MS. It was noticeable that the BSA-MS complex exhibited reduced DPPH radical-scavenging ability, which might be attributed to the restraining effect of BSA on the relevant reaction pathways involved in antioxidation by MS.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOLUTION CHEMISTRY
·
2014
·Vol. 43
·期 3
·585-607
·
IF 1.083
Peng Xin,Sun Yinhe,Qi Wei,Su Rongxin,He Zhimin
UV–vis absorption, fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopic methods were employed to reveal the mechanism of the binding between coenzyme Q 10 (CoQ 10 ) and human serum albumin (HSA) under simulated physiological conditions (pH = 7.4). The binding parameters were calculated by the fluorescence quenching method. The results demonstrate that the fluorescence quenching of HSA by CoQ 10 is mainly static quenching due to the formation of HSA–CoQ 10 complexes, and the number of binding sites ( n ) is equal to 1. The thermodynamic parameters (Δ H
0 = −43.18 kJ·mol −1 , Δ S
0 = −47.05 J·mol −1 ·K −1 , Δ G
0 = −29.15 kJ·mol −1 ) indicate that the enthalpy-driven binding process is favorable, and the main binding forces between CoQ 10 and HSA are hydrogen bonds and van der Waals forces. The competitive experiments using different site markers indicate that subdomain IIA (site I) of HSA is the primary binding site for CoQ 10 . The average binding distance ( r ) between HSA and CoQ 10 is 4.29 nm, which was estimated according to the Förster’s theory of non-radiation energy transfer. In addition, the UV–vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid fluorescence, CD spectra, and FT-IR spectroscopy data show slight conformational changes of HSA in the presence of CoQ 10 . These findings provide valuable binding information between HSA and CoQ 10 , which may be beneficial to pharmacokinetics research and could be used to design the dosage form of CoQ 10 .
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2015
·Vol. 10
·期 4
·e0118274
·
IF 3.234
Xin Peng,Wei Qi,Renliang Huang,Rongxin Su,Zhimin He
Salvianolic acid B and rosmarinic acid are two main water-soluble active ingredients from Salvia miltiorrhiza with important pharmacological activities and clinical applications. The interactions between salvianolic acid B (or rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of gold nanoparticles (Au NPs) with three different sizes were investigated by using biophysical methods for the first time. Experimental results proved that two components quenched the fluorescence of BSA mainly through a static mechanism irrespective of the absence or presence of Au NPs. The presence of Au NPs decreased the binding constants of salvianolic acid B with BSA from 27.82% to 10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from 0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs (caused by a noncompetitive binding between Au NPs and drugs at different albumin sites) induced changeable affinity and binding distance between drugs and BSA compared with no Au NPs. The competitive experiments revealed that the site I (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and rosmarinic acid. Additionally, two compounds may induce conformational and micro-environmental changes of BSA. The results would provide valuable binding information between salvianolic acid B (or rosmarinic acid) and BSA, and also indicated that the Au NPs could alter the interaction mechanism and binding capability of drugs to BSA, which might be beneficial to understanding the pharmacokinetics and biological activities of the two drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2015
·Vol. 6
·期 8
·2712-2726
·
IF 2.791
Xin Peng,Xiangchao Wang,Wei Qi,Renliang Huang,Rongxin Su,Zhimin He
Rosmarinic acid (RA) is an importantly and naturally occurring polyphenol from plants of the mint family with potent biological activities. Here, the in vitro interaction of RA with bovine serum albumin (BSA) has been investigated using various biophysical approaches as well as molecular modeling methods, to ascertain its binding mechanism and conformational changes. The fluorescence results demonstrated that the fluorescence quenching of BSA by RA was mainly the result of the formation of a ground state BSA–RA complex, and BSA had one high affinity RA binding site with a binding constant of 4.18 × 104 mol L−1 at 298 K. Analysis of thermodynamic parameters revealed that hydrophobic and hydrogen bond interactions were the dominant intermolecular force in the complex formation. The primary binding site of RA in BSA (site I) had been identified by site marker competitive experiments. The distance between RA and the tryptophan residue of BSA was evaluated at 3.12 nm based on Förster's theory of non-radiation energy transfer. The UV-vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectra confirmed that the conformation and structure of BSA were altered in the presence of RA. Moreover, the nuclear magnetic spectroscopy showed that the aromatic groups of RA took part in the binding reaction during the BSA–RA complexation. In addition, the molecular picture of the interaction mechanism between BSA and RA at the atomic level was well examined by molecular docking and dynamics studies. In brief, RA can bind to BSA with noncovalent bonds in a relatively stable way, and these findings will be beneficial to the functional food research of RA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2015
·
IF 3.391
Xin Peng,Xiangchao Wang,Wei Qi,Rongxin Su,Zhimin He
Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. The interaction between RA and human serum albumin (HSA) was investigated by multi-spectroscopic, electrochemistry, molecular docking and molecular dynamics simulation methods. The fluorescence emission of HSA was quenched by RA through a combined static and dynamic quenching mechanism, but the static quenching was the major constituent. Fluorescence experiments suggested that RA was bound to HSA with moderately strong binding affinity through hydrophobic interaction. The probable binding location of RA was located near site I of HSA. Additionally, as shown by the Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra, RA can result in conformational and structural alterations of HSA. Furthermore, the molecular dynamics studies were used to investigate the stability of the HSA and HSA–RA system. Altogether, the results can provide an important insight for the applications of RA in the food industry.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
·
IF 5.3
Xiao-Lin Xie,Zhao Zhang,Wen Xiong,Jie Wang,Wei Gong,Wen Xu,Shuang Cai,Jing Li
Carbon dots (CDs) prepared from biomass usually produce poor quantum yield and reproducibility. A fine separation of raw materials may enhance the fluorescence performance. In this work, embryos of cumin seeds were precisely chosen as the carbon source to prepare (CDs) through hydrothermal method. The obtained product (CDs-E) possessed a higher quantum yield of 10.60 % than those synthesized with testas or whole seeds, which may be due to the relatively smaller particle size and more C-N functional groups. Rutin, as a common natural active component, could quench the fluorescence of CDs-E notably through internal filtering effect. Herein, a highly selective fluorescent sensor based on CDs-E for detecting rutin was proposed with a linearity range of 0.05 ∼ 30 μM and a detection limit of 0.015 μM obtained. Additionally, the developed method was successfully applied for the detection of rutin in Flos Sophorae , rutin tablets and capsules. This work showed the significance of fine classification for natural carbon source in preparation of CDs and provided a feasible method for quality monitoring of rutin-related pharmaceuticals, health care products and traditional Chinese medicinal materials.
✓ 已验证
产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Huilin Liu,Chao Huang,Zhenni Liu,Yuhan Li,Yanan Zhu,Min Gao,Jing Chen,Hui Zhang,Zhengtao Xiao,Wei Zhao
Background and Purpose Cardiac glycosides (CGs), traditionally prescribed for heart failure and arrhythmias, show anticancer potential. However, their mechanisms for preferential inhibition of tumour tissue and constituent malignant cells are not fully elucidated. This study aims to elucidate the therapeutic benefits of CGs in targeting specific tumours and dissect their multi-targeting mechanisms that confer their cytotoxicity against malignant cells. Experimental Approach We designed an integrated workflow to identify therapeutic CGs with high toxicity to certain cancers, investigating their multi-target effects, assessing their toxicity to malignant cells and analysing the prognostic relevance of CGs' target genes. The computational findings were confirmed through gene knockdown, cell viability assays, reactive oxygen species (ROS) measurements and so forth. Key Results CGs modulate multiple genes crucial for ion homeostasis, oxidative stress and apoptosis, with a particularly strong inhibitory effects on uveal melanoma (UVM). Notably, digitoxin suppresses UVM cell proliferation and induces ROS levels by simultaneously targeting STAT3 and KLF5. Single-cell transcriptomic analysis revealed that malignant cells are likely more vulnerable to CGs due to their higher expression of CG target genes compared with surrounding cells in the UVM microenvironment. Conclusions and Implications Given UVM's limited options, our study highlights the potential of digitoxin as a promising novel therapeutic agent for this aggressive and rare ocular cancer. Our comprehensive approach is effective in identifying the potent, cancer-specific therapeutic agents from herbal plants.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
·
IF 3.8
Wu Huaxin,Huang Ting,Zhang Wei,Yao Huan,Li Xueyao,Su Ping,Yang Yi
In the biomedical and chemical fields, purity assessment of compounds is a critical step in ensuring product quality and safety. In this study, a method for purity quantification was proposed as two-signal suppression–internal standard correction–high-performance liquid chromatography–quantitative nuclear magnetic resonance (TSS-ISC-HPLC-qNMR). The two-signal suppression effectively suppresses the interference of solvent signals in the NMR spectra, and the internal standard correction eliminates the influence of many variables during sample preparation and analysis. The purity result (99.89%) of the quantification of certified reference material of acesulfame (AF) by this method matched with the certified value (99.88%), which verified the accuracy of the method. The purity result (with standard deviation) of 94.42% ± 0.10% for the quantification of the low-purity drug digitoxin by the method matched with the purity result of 94.42% ± 0.11% by qNMR with deconvolution (as a validated method), which proved that the method could be used for the quantification of low-purity compounds. The methodology achieved a substantial reduction in total analysis time, from 28 to 4 h (considering only the routine analysis time after optimization), in contrast to the ISC-HPLC-qNMR approach. Additionally, it effectively decreased bias to undetectable with a standard deviation of 0.10%, while the bias of the TSS-HPLC-qNMR method was 0.93%. The present method ensures the accuracy of the quantitative results while demonstrating a low economic burden and significant time efficiency, which shows great potential for application in the accurate quantitative analysis of low-purity organic compounds. Graphical
✓ 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）