查找使用阿拉丁产品的科研文献

Novel Reductive Responsive Chrysin-Oligomeric Hyaluronic Acid Nanomaterials to Curcumin Delivery for Cancer Therapy

Wang Bingjie,Ma Chuanjiang,Guo Chunjing,Wang Kaili,Yuan Dehao,Cheng Haoran,Liu Mengna,Fang Lei,Fan Xinxin,Chen Daquan

Drug resistance, perplexing a lot of doctors and patients, was an inevitable challenge in the field of effective cancer therapy. Poor water solubility, inefficient aggregation at tumor site and killing normal cells were also the great obstacles, which gave rise to failure in the tumor clinical treatment. In order to overcome these difficulties, modified targeting nano-micelles (MT-NMs) loading Curcumin (Cur) and Chrysin (Chr) were designed. In this work, dithiodipropionic acid (DA), a reduction-sensitive material, acted as a "messenger" linker connecting Chr and oligomeric hyaluronic acid (oHA). Then, the amphiphilic polymer, oligomeric hyaluronic acid-dithiodipropionic acid-Chrysin (oHA-DA-Chr), was synthesized. What's more, combinational therapy is a better way to cripple cancer drug-resistant and reinforce the therapeutic efficacy. In this study, 1H-NMR was used to authenticate the structure of oHA-DA-Chr. The amphiphilic oHA-DA-Chr could self-assemble into nano-micelles (NMs) in water. The NMs with small size (223.2±2.4 nm) could concentrate well at tumor sites by enhancing permeability and retention effect (EPR) and CD44 receptor targeting property of oHA. The Cur could release well from NMs when disulfide bond (S–S) of DA was exposed to tumor environment containing high concentration of glutathione (GSH).

Effects of Baicalein and Chrysin on the Structure and Functional Properties of β-Lactoglobulin

Ang Li,Lei Chen,Weijie Zhou,Junhui Pan,Deming Gong,Guowen Zhang

Two flavonoids with similar structures, baicalein (Bai) and chrysin (Chr), were selected to investigate the interactions with β-lactoglobulin (BLG) and the influences on the structure and functional properties of BLG by multispectral methods combined with molecular docking and dynamic (MD) simulation techniques. The results of fluorescence quenching suggested that both Bai and Chr interacted with BLG to form complexes with the binding constant of the magnitude of 105L·mol−1. The binding affinity between BLG and Bai was stronger than that of Chr due to more hydrogen bond formation in Bai–BLG binding. The existence of Bai or Chr induced a looser conformation of BLG, but Chr had a greater effect on the secondary structure of BLG. The surface hydrophobicity and free sulfhydryl group content of BLG lessened due to the presence of the two flavonoids. Molecular docking was performed at the binding site of Bai or Chr located in the surface of BLG, and hydrophobic interaction and hydrogen bond actuated the formation of the Bai/Chr–BLG complex. Molecular dynamics simulation verified that the combination of Chr and BLG decreased the stability of BLG, while Bai had little effect on it. Moreover, the foaming properties of BLG got better in the presence of the two flavonoids compounds and Bai improved its emulsification stability of the protein, but Chr had the opposite effect. This work provides a new idea for the development of novel dietary supplements using functional proteins as flavonoid delivery vectors.Keywords:baicalein;chrysin;β-lactoglobulin;functional property;spectrophotometry;molecular dynamics simulation

Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives

Xiangping Deng,Zihao Zhao,Shujuan Xiong,Runde Xiong,Juan Liu,Zhe Wang,Liu Zou,Xiaoyong Lei,Xuan Cao,Zhizhong Xie,Yanming Chen,Xing Zheng,Yunmei Liu,Guotao Tang

Sodium Oleate-Based Nanoemulsion Enhances Oral Absorption of Chrysin through Inhibition of UGT-Mediated Metabolism

Dong Dong,Enxi Quan,Xue Yuan,Qian Xie,Zhijie Li,Baojian Wu

Oral bioavailability of flavonoids (and many phenolic drugs) is severely limited by extensive first-pass glucuronidation. Here we aimed to determine the modulatory effects of commonly used pharmaceutical excipients (PEs) on UDP-glucuronosyltransferase (UGT) activities and to evaluate the potential of nanoemulsions containing a UGT-inhibitory PE for oral absorption enhancement of chrysin, a model flavonoid. The effects of PEs on glucuronidation were determined using tissue (liver and intestine) microsomes, expressed UGT1A1 enzyme, and UGT1A1-overexpressing HeLa cells. Nanoemulsions were prepared using a modified emulsification technique and subsequently characterized by particle size, zeta-potential, morphology, and in vitro drug release. Pharmacokinetic studies were performed with rats to assess the effects of nanoemulsions on the metabolism and pharmacokinetics of chrysin. Of 21 PEs, five (i.e., Brij 35, Brij 58, labrasol, sodium oleate, and Tween 20) significantly inhibited chrysin glucuronidation. Of note, sodium oleate was the most potent inhibitor of glucuronidation. Eight PEs including Tween 80 had no effects on glucuronidation of chrysin. The chrysin nanoemulsions prepared with sodium oleate (named SO-NE) were spherical or near-spherical (particle size, 83.2 nm; zeta-potential, −43.7 mV; entrapment efficiency, 89.5%). The reference nanoemulsions prepared with Tween 80 (T80-NE) were highly similar to SO-NE in terms of particle size, zeta-potential, and drug release. It was demonstrated in pharmacokinetic studies that SO-NE led to a 4.3-fold increase in systemic exposure of chrysin and a 3.5-fold increase in Cmax value, whereas T80-NE did not cause any changes in chrysin pharmacokinetics. In conclusion, sodium oleate-based nanoemulsions greatly enhanced oral absorption of chrysin. Oral absorption enhancement of chrysin was attained through targeted inhibition of first-pass glucuronidation by sodium oleate.

Fluorescent molecularly imprinted polymer based on sugarcane-derived carbon quantum dots for the detection of Chrysin

Ao Qian,Zhenyang Rao,Jiaqi Guo,Yi Kuang,Shengxiang Yang,Xu Han

Chrysin (5,7-dihydroxyflavone) is a bioactive flavonoid whose selective detection in complex matrices remains challenging. Herein, a green fluorescent molecularly imprinted polymer (SCQDs@FMIPs) was developed using sugarcane bagasse–derived carbon quantum dots (SCQDs) as the core. SCQDs with excellent fluorescence were synthesized hydrothermally and functionalized with KH550 to enhance surface reactivity. Using chrysin as the template, SCQDs@FMIPs were prepared via a sol–gel process, exhibiting high photostability and specific recognition. The sensor achieved rapid fluorescence quenching within 5 min and a low detection limit of 2.54 × 10 −4  g/L, surpassing non-imprinted polymers. Mechanistic studies revealed dynamic quenching with partial FRET contribution. SCQDs@FMIPs displayed strong selectivity against structural analogs and ions, with satisfactory recoveries (73.43–128.06%) in real samples. This work demonstrates a sustainable, low-cost, and efficient strategy for chrysin detection, highlighting the value of agricultural waste in advanced sensing applications.

Sensitive, simultaneous determination of chrysin and baicalein based on Ta2O5-chitosan composite modified carbon paste electrode

Zhengkun Xie,Gaiping Li,Yamin Fu,Mengjiao Sun,Baoxian Ye

Chrysin and baicalein are the major flavonoids found in oroxylum indicum, an essential herb in traditional Chinese medicine (TCM). Owing to their similar characteristics and physiochemical property, it is a great challenge to detect both of them simultaneously. In this work, tantalum oxide (Ta 2 O 5 ) particles and chitosan modified carbon paste electrode (Ta 2 O 5 -CTS-CPE) was prepared and characterized by scanning electron microscope (SEM), X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV) and electrochemical impedance spectrum(EIS). Under the optimum conditions, the prepared Ta 2 O 5 -CTS-CPE exhibited excellent electrocatalytic activity toward the oxidation of chrysin and baicalein, and it could serve as the sensor for highly sensitive and simultaneous determination both of them. The linear range is 0.08–4.0   μM for both of them, and the detection limits were determined to be 0.03 and 0.05   μM (S/N=3) for chrysin and baicalein, respectively. Furthermore, the proposed electrochemical sensor displayed high sensitivity, excellent stability and got satisfactory results in oroxylum indicum samples analysis.

Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction

Yang Mei,Xiong Jun,Zou Qiang,Wang Dan-Dan,Huang Cong-Xin

Interstitial fibrosis after acute myocardial infarction (MI) leads to cardiac structural remodeling and dysfunction. The peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist chrysin has been shown to protect injured myocardium through suppression of oxidative stress and inflammation. This study was designed to investigate the effect and mechanism of chrysin on myocardial fibrosis. A rat MI model was created by ligating the left coronary artery. The rats with MI were treated with chrysin (40 mg/kg/day) or 0.5% carboxymethylcellulose sodium by intragastric administration for 4 weeks after operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed in vitro. Echocardiography showed that cardiac function was significantly improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up-regulated PPAR-γ and inhibited the nuclear factor-kappa B (NF-κB) pathway by suppressing inhibitor kappa B kinase β phosphorylation. Immunohistochemistry analysis and PCR detected downregulated expression of AP-1 after chrysin treatment. Chrysin also markedly reduced the increased α-SMA, typeland type III collagen expression of CFs mediated by AngII in vitro. In conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct peripheral zone after MI. The underlined mechanism may be the up-regulation of PPAR-γ and inhibition of the NF-κB and AP1 pathway.

Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide

Enxi Quan,Huailing Wang,Dong Dong,Xingwang Zhang,Baojian Wu

Active transport of glucuronide out of cells is a critical process in elimination of drugs via the glucuronidation pathway. Here, HeLa cells were stably transfected with UGT1A1 and the contributions of BCRP and MRP family transporters to the cellular efflux of chrysin glucuronide (CG) were determined. The cDNA of UGT1A1 was introduced into HeLa cells using the lentiviral transfection method. The modified cells were functional in generation of the glucuronide from chrysin. Ko143 at 10–20 μM (a dual inhibitor of BCRP and UGT1A1) caused a marked decrease (51.3%–59.7%, P < 0.01) in the excretion rate and efflux clearance of CG. Likewise, MK-571 at 5–20 μM (an inhibitor of MRPs but an activator of UGT1A1) resulted in a significant reduction in the excretion rate (18.2%–64.0%, P < 0.01) and efflux clearance (37.0%–90.2%, P < 0.001). By contrast, dipyridamole and leukotriene C4 showed no inhibitory effects on CG excretion. The chemical inhibition indicated that excretion of CG was contributed by the MRP family transporters, whereas the role of BCRP was unclear. Furthermore, short hairpin RNA–mediated silencing of a target transporter led to a marked reduction in the excretion rate of CG (38.6% for BCRP, 39.3% for MRP1, 36.4% for MRP3, and 28.7% for MRP4; P < 0.01). Transporter silencing also led to substantial decreases in the efflux clearance (44.7% for BCRP, 60.4% for MRP1, 36.7% for MRP3, and 28.7% for MRP4; P < 0.01). The gene silencing results suggested that BCRP, MRP1, MRP3, and MRP4 were significant contributors to excretion of CG.

GSH-Responsive Co-Delivery of Chrysin and 3-Methyladenine Disrupts Tumor Adaptive Stress for Synergistic Antitumor Therapy

Kong Wenbin,Su Baoqiang,Gu Han,Huang Weiqiang,Wang Jing,Zhu Yaqi,Xu Rongrong,Tong Dali,Xu Weiping

Cancer remains a major global health challenge, and conventional therapies are still limited by poor tumor specificity, therapeutic resistance, and systemic side effects. Herein, we developed a glutathione (GSH)-responsive FFSSFF coacervate system for the codelivery of chrysin (CH) and the autophagy inhibitor 3-methyladenine (3-MA) to induce tumor-selective autophagic stress. CH activated endoplasmic reticulum stress and promoted autophagy through the GRP78/PERK and Akt/mTOR signaling pathways, while 3-MA simultaneously disrupted autophagic flux, leading to intracellular homeostasis imbalance, mitochondrial dysfunction, excessive reactive oxygen species accumulation, and tumor cell death. The resulting CH/3-MA@FFSSFF coacervates exhibited favorable physicochemical properties, GSH-responsive behavior, efficient intracellular uptake, and selective accumulation in tumor cells. Both in vitro and in vivo experiments demonstrated potent antitumor activity of the CH/3-MA@FFSSFF system. In particular, in an orthotopic lung cancer model, CH/3-MA@FFSSFF effectively suppressed tumor growth, prolonged median survival time, and inhibited tumor cell migration and invasion. Collectively, this study presents a promising liquid–liquid phase separation-derived coacervate platform for targeted combinational cancer therapy through the induction of autophagic stress, with enhanced therapeutic efficacy and reduced off-target toxicity.

Inhibitory mechanism of chrysin and diosmetin to α-glucosidase: insights from kinetics, multispectroscopy and molecular docking investigations

Yuqing Zhang,Yaping Li,Yuhan Zhai,Xing Zhao,Mingxing Lv,Shaoxuan Yu,Haifang Xiao,Yuanda Song

Inhibition of α-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on α-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited α-glucosidase activity with IC50 value of 26.445 ± 1.406 μmol L−1 and 18.380 ± 1.264 μmol L−1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against α-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 ± 0.04) ×10−4 mol L−1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of α-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of α-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-α-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma

Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway

Yu Li,Ximei Wang

Purpose High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment.Materials and Methods Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2’-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability.Results Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway.Conclusion Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.

Synthesis, characterization and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and EGFR downregulation

Yun-Mei Liu,Yang Li,Rong-Fang Liu,Jie Xiao,Bin-Ning Zhou,Qi-Zhi Zhang,Jian-Xin Song

Chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities. Among them, N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)valeryl)-L-leucine (8c) displayed the most remarkable inhibitory activities against MCF-7 cells with IC50 values of 16.6 μM. Preliminary mechanistic studies showed that 8c could inhibit the colony formation and migration of MCF-7 cells. Flow cytometry analysis demonstrated that 8c mediated cell apoptosis and the prolongation of cell cycle progression in G1/S-phase against MCF-7 cells. Besides, 8c displayed the moderate inhibition against EGFR. Western blot assay suggested that 8c significantly inhibited EGFR phosphorylation. Molecular docking showed that 8c can bind the EGFR kinase well.