Frontiers in Pharmacology
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2021
·
IF 5.811
Li Pengfei,Peng Jun,Li Yuexin,Gong Lili,Lv Yali,Liu He,Zhang Tianhong,Yang Song,Liu Hongchuan,Li Jinglai,Liu Lihong
Background: Akebia saponin D (ASD) has a variety of biological activities and great medicinal potential, but its oral bioavailability is so low as to limit its development. Its pharmacokinetic profiles and excretion and metabolism in vivo have not been fully elucidated. This study was an attempt in this area.Methods: A simple LC-MS/MS method to simultaneously quantify ASD and its metabolites M1∼M5 in rat plasma, feces, urine and bile was established with a negative ESI model using dexketoprofen as the internal standard. Meanwhile, the UPLC-HR/MS system was used to screen all possible metabolites in the urine, feces and bile of rats, as compared with blank samples collected before administration. Absolute quantitative analysis was for M0, M3, M4, and M5, while semi-quantitative analysis was for M1, M2, and Orbitrap data.Results: The AUC0-t values after intravenous administration of 10 mg/kg and intragastrical administration of 100 mg/kg ASD were 19.05 ± 8.64 and 0.047 ± 0.030 h*μg/ml respectively. The oral bioavailability was determined to be extremely low (0.025%) in rats. The exposure of M4 and M5 in the oral group was higher than that of M0 in the terminal phase of the plasma concentration time profile, and ASD was stable in the liver microsome incubation system of rats, but metabolism was relatively rapid during anaerobic incubation of intestinal contents of rats, suggesting that the low bioavailability of ASD might have been attributed to the poor gastrointestinal permeability and extensive pre-absorption degradation rather than to the potent first pass metabolism. This assertion was further verified by a series of intervention studies, where improvement of lipid solubility and intestinal permeability as well as inhibition of intestinal flora increased the relative bioavailability to different extents without being changed by P-gp inhibition. After intravenous administration, the cumulative excretion rates of ASD in the urine and bile were 14.79 ± 1.87%, and 21.76 ± 17.61% respectively, but only 0.011% in feces, suggesting that the urine and bile were the main excretion pathways and that there was a large amount of biotransformation in the gastrointestinal tract. Fifteen possible metabolites were observed in the urine, feces and bile. The main metabolites were ASD deglycosylation, demethylation, dehydroxylation, decarbonylation, decarboxylation, hydroxylation, hydroxymethylation, hydroxyethylation and hydrolysis.Conclusion: The pharmacokinetics, bioavailability, metabolism and excretion of ASD in rats were systematically evaluated for the first time in this study. It has been confirmed that the ultra-low oral bioavailability is due to poor gastrointestinal permeability, extensive pre-absorption degradation and biotransformation. ASD after iv administration is not only excreted by the urine and bile, but possibly undergoes complex metabolic elimination.
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JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Hongjun Zang,Jing Lou,Shuolei Jiao,Huanxin Li,Yannan Du,Jiao Wang
Chitin and its derivatives contain biologically fixed nitrogen elements, which can provide nitrogen sources for N-containing chemicals. Herein, a series of pyridinium-based ionic liquids were synthesized to directly catalyze the conversion of N -acetyl-D-glucosamine (NAG, the monomer of chitin) to 3-acetamido-5-acetylfuran (3A5AF). The yield of 3A5AF in 1-carboxymethyl pyridinium chloride ionic liquid reached 37.49%, without any additives. Using B 2 O 3 and CaCl 2 as additives, the optimum yield increased to 67.37% at 180 °C in 20 min. In addition, HPLC-MS analysis has been utilized to elucidate the reaction mechanism. This research on turning “waste” into “wealth” opens up new ways for the utilization of biomass waste, which not only reduces environmental pollution but also has potential economic value.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2020
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IF 4.192
Xutian Zheng,Chaolun Liu,Jiye Hu
Since 2,4-dichlorophenoxy acetic acid (2,4-D) was discovered in the 1940s, 2,4-D and its derivatives remain among most commonly used herbicides in the world. There have been recent increases in using 2,4-D products in a combination with other herbicides such as metribuzin and acetochlor to control noxious weeds. However, accurate analysis of 2,4-D isooctyl ester remains to be improved due to long analysis time and rapid conversion of the ester to acid (i.e., under-reporting residues). In this work, a simple hydrolysis procedure was introduced to provide a quantitative hydrolytic rate of the ester (>95%) and did not affect the other pH-sensitive compounds. Analysis parameters and sample pretreatments were optimized for improved selectivity and accuracy. The hydrolysis-QuEChERS (quick, easy, cheap, effective, rugged, and safe) technique for multidetermination of 2,4-D isooctyl ester, metribuzin, acetochlor, and 2-ethyl-6-methylaniline in corn and soybeans via high performance liquid chromatography–tandem mass spectrometry was established. The method had average recoveries of 74–109% with relative standard deviations ≤13.5% and limits of quantifications (LOQs) of 0.05 mg/kg. The terminal residues of these compounds found in real edible matrixes were less than the corresponding LOQs at harvest time. The risk quotients were far below 100%, indicating a low health risk to consumers.
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BMC Complementary Medicine and Therapies
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2020
·Vol. 20
·期 1
·1-13
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IF 0
Xie Dandan,Jiang Liqin,Lin Yao,Liu Zhenwei
Background The purpose of this study was to assess the antioxidative activity of selenium-enriched Chrysomyia Megacephala (Fabricius) ( C. megacephala ) larvae powder (SCML) and its impact on the diversity and structure of intestinal microflora in a mouse model of D-galactose (D-gal)-induced oxidative damage. Methods Sixty male ICR mice were equally randomized to a normal control (NC) group, a model group, a positive group, a low-dose SCML (L-SCML) group, a mid-dose SCML (M-SCML) group, and a high-dose SCML (H-SCML) group. Animals in NC and model groups received water, animals in the positive group received 40 mg/Kg vitamin E (VE), and those in the three SCML groups received SCML which include 300, 1000 and 3000 μg/Kg selenium (Se) respectively. An oxidative damage model induced by subcutaneous injection of D-gal for 6 weeks via the neck was established. Serum oxidative stress levels and tissue appearance were evaluated. Tissues oxidative stress levels were detected by commercially available kit. Nuclear erythroid 2-related factor (Nrf2) and gut microbiota were determined by western blot and high throughput sequencing 16S rRNA gene respectively. Results An oxidative damage model was established successfully as represented by a significant elevation of malondialdehyde (MDA) and protein carbonylation, and inhibition of the antioxidants including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and glutathione (GSH). It was found that oxidative damage and histological alterations were attenuated, the expression of Kelch-like ECH-associated protein (Keap1) was decreased, and the expression of Nrf2 and hemeoxygenase-1 (HO-1) was increased after SCML treatment. In addition, significant changes were observed in the gut microbiota, including Proteobacteria and the ratio of Bacteroidetes to Firmicutes at the phylum level, as well as Helicobacter , Clostridium and Lactobacillus at the genus level. Conclusion SCML exerted an antioxidative effect in vivo, probably by increasing the antioxidant activity and reducing the production of oxidation products via the Nrf2 signaling pathway. SCML could also redress the intestinal flora imbalance induced by oxidative stress. All these findings suggest that SCML could serve as a functional food and natural drug additive to protect the human body against oxidative damage.
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ChemSusChem
·
2019
·Vol. 13
·期 4
·803-810
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IF 7.804
Chengyi Zhu,Yannan Zhang,Xiaohua Yu,Peng Dong,Jianguo Duan,Jiaming Liu,Jianxiong Liu,Yingjie Zhang
Graphical Progress towards the positive : A facile strategy through manipulating KMnO 4 concentration is introduced to precisely fabricate 1 D LiMn 2 O 4 nanorods with four distinct diameter gradients. The LiMn 2 O 4 nanorod with a critical diameter of approximately 70–80 nm displays the highest discharge capacity and promising cycling performance. The role of 1 D crystal size in effecting interface chemical species and electrochemical performance is elucidated by comparative characterization methods. The morphology and size of nanoelectrode materials determine their properties. Compared to the bulk structure electrodes, 1 D electrode materials for Li-ion batteries have been intensively studied owing to their excellent Li + diffusion kinetics. It is generally accepted that smaller-sized electrode materials lead to better Li storage kinetics. In this study, this is found to not be the case in 1 D LiMn 2 O 4 positive materials. A facile strategy of manipulating the KMnO 4 concentration is introduced to precisely fabricate 1 D LiMn 2 O 4 nanorods with four distinct diameter gradients from 30 to 170 nm. The role of 1 D crystal size in effecting interface chemical species and electrochemical performance is elucidated by comparative characterization methods. X-ray photoelectron spectroscopy (XPS) Ar-ion etching technology shows that the Mn 2+ is electrochemically inactive on the surface of the sample, which explains the adverse effects observed on LiMn 2 O 4 nanorods with the minimum diameter of 30–40 nm, such as decreased discharge capacity. The LiMn 2 O 4 nanorod with a critical diameter of approximately 70–80 nm displays the highest discharge capacity and promising cycling performance. This work clarifies an important property that has previously been neglected and deepens the understanding for design of Mn-based positive materials.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Chao Zhang,Huai Lan,Liming Yu,Jikai Zhao,Tao Huang,Boxuan Sun,Shan Meng,Jinfeng Duan,Jing Liu,Zijun Zhou,Zhishang Wang,Jiahui Li,Xinyi Huang,Huishan Wang
First to report that radiation-induced atrial fibrillation is driven by cellular senescence. • The GATA4-NF-κB-SASP axis is the key signaling pathway mediating this process. • Senolytic therapy with D/Q (Dasatinib+Quercetin) rescues atrial remodeling and reduces AF susceptibility. • Targeting senescence with senolytics offers a promising strategy to prevent radiation-induced AF. Radiation-induced heart disease is a well-recognized complication of thoracic radiotherapy, with atrial fibrillation (AF) being a particularly notable sequela. The mechanisms by which ionizing radiation (IR) heightens susceptibility to AF remain inadequately understood. This study seeks to elucidate the role of cellular senescence and the GATA4-NF-κB signaling pathway in radiation-induced atrial remodeling and the pathogenesis of AF. An in vivo mouse model was developed through localized cardiac irradiation using 20 Gy X-rays. The irradiated mice demonstrated dose-dependent atrial structural and electrophysiological remodeling. Transcriptomic analysis revealed significant enrichment in DNA damage response (DDR), NF-κB signaling, and aging-related pathways. IR exposure induced substantial DNA damage, activated ATM/ATR pathways, and enhanced autophagic flux. These responses culminated in the accumulation of GATA4 and phosphorylation of NF-κB, which drove the expression of the senescence-associated secretory phenotype (SASP), coinciding with increased senescence-associated β-galactosidase (SA-β-gal) activity. In vitro , these crucial findings were recapitulated using irradiated HL-1 atrial cardiomyocytes, whereas the knockdown of GATA4 effectively suppressed both cellular senescence and SASP expression. Notably, treatment with the senolytic combination of dasatinib and quercetin (D/Q) alleviated DNA damage, inhibited excessive autophagy, and suppressed the GATA4-NF-κB pathway in irradiated mice, thereby reducing SASP levels. These improvements resulted in the reversal of atrial structural and electrophysiological remodeling and a marked reduced susceptibility to AF. Overall, our findings demonstrate that IR promotes atrial remodeling by inducing DNA damage-mediated cellular senescence via the GATA4-NF-κB-SASP axis. Targeting this pathway with senolytics such as D/Q thus identifies a promising therapeutic strategy for preventing radiation-induced atrial fibrillation.
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Journal of Oleo Science
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2023
·
IF 1.5
Ting Wu,Yueqing Xie,Zhikai Wu,Yifei Li,Mingzhen Jiang,Hongsen Yu,Xuhai Li,Jingjing Wang,Ershun Zhou,Zhengtao Yang
Acute liver injury (ALI), posing a serious threaten to our life, has emerged as a public health issue around the world. β-carotene has plenty of pharmacologic effects, such as anti-inflammatory, antioxidant, and antitumor activities. In this study, we focused on studying the protective role and potential molecular mechanisms of β-carotene against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced ALI. Our results indicated that β-carotene pretreatment effectively hindered abnormal changes induced by LPS/D-GalN in liver histopathology. Meanwhile, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were downgraded with β-carotene pretreatment. β-carotene pretreatment also decreased malondialdehyde content and myeloperoxidase activity, increased glutathione peroxidase and superoxide dismutase levels, and reduced the levels of tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) in liver tissues. Further investigations found that β-carotene mediated multiple signaling pathways in LPS/D-GalN-induced ALI, inhibiting NF-κB and MAPK signaling and upregulating the expression of Nrf2 and HO-1 proteins. All findings indicate that β-carotene appears to protect mice against LPS/D-GalN induced ALI by reducing oxidative stress and inflammation, possibly via regulating NF-κB, MAPK, and Nrf2 signaling.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Yanli Wang,Siwei Zhong,Ke Yang,Ruifeng Luo,Linxin Dai,Wenzhen Zhong,Yan Ye,Chaomei Fu,Dasheng Lin,Nan Li,Jianping Chen,Chuan Zheng,Shu Fu,Fei Gao
Herein, a β-1,3- D -glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral “nano-in-micro” advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the “nests”-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of β-1,3- D -glucan by β-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.
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Advanced Healthcare Materials
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2023
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IF 10
Hanru Zhang,Zhiyu Wu,Jingjing Zhou,Zhaopeng Wang,Changyan Yang,Panpan Wang,Muhammad Subaan Fareed,Yuhang He,Jie Su,Ruitao Cha,Kairong Wang
Peptide hydrogels were believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and three-dimensional (3D) printability. Most of the previously reported polypeptide hydrogels are composed of L-peptides, while the hydrogels formed by self-assembly of D-peptides are rarely reported. Herein, we reported a peptide hydrogel constructed by D-J-1, which was the all-D-enantiomer of antimicrobial peptide Jelleine-1. Field emission scanning electron microscope (FE-SEM) and rheologic study were performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies were carried out to evaluate its biofunction. Our results showed that D-J-1 hydrogel was formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π-π stacking force of aromatic ring in the structure of D-J-1. It exhibited promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibited good biocompatibility. Notably, D-J-1 hydrogel showed improved in vitro and in vivo stability when compared with its L-enantiomer J-1 hydrogel. Therefore, the present study would provide new insight into the application of D-peptide hydrogel, and provide a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use. This article is protected by copyright. All rights reserved
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OPTICS AND LASER TECHNOLOGY
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2023
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IF 5
Ke Yang,Zhengkun Wang,Jie Zhang
To address the non-uniformity of hotspots and large background noise signals in the Raman spectrum of traditional surface-enhanced Raman scattering (SERS) probes, this paper presents a high-sensitivity and high-uniformity D-shaped fiber (DSF) SERS probe. The probe is prepared by transferring monolayer silver nanoparticles (AgNPs) with different particle sizes onto the DSF using a liquid-liquid interface method. The electromagnetic distribution on the DSF SERS probe is analyzed with FDTD (finite difference time domain) Solutions simulation software, and the corresponding theoretical enhancement factors are calculated. The DSF SERS probe decorated by AgNPs with a diameter of 100 nm exhibits the largest electric field value among our prepared samples. The experiments are conducted to compare two collection methods with backward and vertical directions The results show that vertical collection offers better Raman enhancement due to the suppression of background noise of the fiber, with a limit of detection (LOD) of 10 −11 mol/L for Rhodamine 6G (R6G). The experimental analytical enhancement factor (AEF) at 611 cm −1 is 1.7 × 10 9 . Furthermore, the multi-molecular detection performance of the DSF SERS probe is experimentally studied and realized successfully.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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2019
·Vol. 46
·期 12
·1194-1200
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IF 2.336
Di Wu,Wei Zhang,Ying Chen,Hong Ma,Mengchang Wang
Multiple myeloma (MM) is a malignancy characterized by the proliferation of malignant plasma cells. Platycodin D (PLD) is a triterpenoid saponin that exerts anti-tumour activity through multiple mechanisms. However, the role of PLD in MM remains unknown. Here, we investigated the effect of PLD on MM cell lines NCI-H929 and U266B1, and elucidated the underlying molecular mechanism. Cell Counting Kit-8 assay showed that the proliferation of NCI-H929 and U266B1 cells was significantly decreased after PLD treatment. Transwell assay confirmed that PLD treatment suppressed migration of NCI-H929 and U266B1 cells. Flow cytometry results indicated that the apoptotic rates of bortezomib (BTZ)-treated NCI-H929 and U266B1 cells were markedly increased after PLD treatment. Western blot analysis revealed that bcl-2 expression was decreased, while bax expression was increased in PLD-treated NCI-H929 and U266B1 cells compared with that in BTZ-treated cells. Furthermore, PLD treatment blocked the activation of nuclear factor-kappa B (NF-κB) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling pathways in NCI-H929 cells. Taken together, these data showed that PLD inhibited proliferation and migration, and enhanced chemosensitization to BTZ through inactivation of the NF-κB and JAK2/STAT3 pathways in MM cell lines. These findings indicated that PLD might serve as a novel therapeutic agent for the treatment of MM.
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PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2018
·Vol. 20
·期 26
·17942-17951
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IF 3.906
Muge Niu,Yucui Hou,Weize Wu,Shuhang Ren,Ru Yang
Vanadium(V)-catalyzed aerobic oxidation in aqueous solution shows high selectivity in the field of C–C bond cleavage of carbohydrates for chemicals with less carbon atoms. However, the pathway of C–C bond cleavage from carbohydrates and the conversion mechanism are unclear. In this work, we studied the pathway and the mechanism of D-glucose oxidation to formic acid (FA) in NaVO3–H2SO4 aqueous solution using isotope-labeled glucoses as substrates. D-Glucose is first transformed to FA and D-arabinose via C1–C2 bond cleavage. D-Arabinose undergoes similar C1–C2 bond cleavage to form FA and the corresponding D-erythrose, which can be further degraded by C1–C2 bond cleavage. Dimerization and aldol condensation between carbohydrates can also proceed to make the reaction a much more complicated mixture. However, the fundamental reaction, C1–C2 bond cleavage, can drive all the intermediates to form the common product FA. Based on the detected intermediates, isotope-labelling experiments, the kinetic isotope effect study and kinetic analysis, this mechanism is proposed. D-Glucose first reacts with a vanadium(V) species to form a five-membered-ring complex. Then, electron transfer occurs and the C1–C2 bond weakens, followed by C1–C2 bond cleavage (with no C–H bond cleavage), to generate the H3COO˙–vanadium(IV) complex and D-arabinose. FA is generated from H3COO˙ that is oxidized by another vanadium(V) species. The reduced vanadium species is oxidized by O2 to regenerate to its oxidation state. This finding will provide a deeper insight into the process of C–C bond cleavage of carbohydrates for chemical synthesis and provide guidance for screening and synthesizing new highly-efficient catalyst systems for FA production.
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