Toxics
·
2024
·Vol. 12
·期 11
·810
·
IF 3.9
Xiangsheng Tian,Yiquan Ou,Shengyuan Shi,Qiuhua Zhou,Sihong Long,Yao Xiang,Weichao Zhao,Dingxin Long
This study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) stress and impaired autophagy. In this experiment, adult hens were assigned to one of four groups: Control, Resv, TOCP, and TOCP + Resv. The spinal cord tissues were examined through transmission electron microscopy, hematoxylin and eosin (HE) staining, Nissl staining, and Western blotting to evaluate key proteins associated with ER stress and autophagy. Additionally, RT-qPCR and immunofluorescence were employed to measure sirtuin1 (SIRT1) expression. The findings revealed that TOCP induced severe ultrastructural damage, including disrupted myelin sheaths, dilated ER, and extensive neurodegeneration, as confirmed by histological evaluations. The expression levels of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, Beclin-1, P62, and LC3-II were also significantly elevated by TOCP. However, Resv treatment markedly attenuated these pathological changes by reducing ER stress, restoring autophagic flux, and upregulating SIRT1 expression, preserving spinal cord integrity. These results indicate that Resv can effectively counteract TOCP-induced neurotoxicity by modulating ER stress and autophagy, underscoring its potential as a therapeutic agent for neuroprotection.
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ACS Pharmacology & Translational Science
·
2024
·
IF 4.9
Shuo Yu,Lu Zhang,Yanshen Yang,Meijuan Wang,Tingting Liu,Wenwen Ji,Yang Liu,Hao Lv,Yang Zhao,Xi Chen,Tinghua Hu
The dense storm microenvironment formed by an excessively cross-linked extracellular matrix, such as hyaluronic acid and collagens, serves as a major barrier that prevents drugs from reaching the deeper tumor. Current traditional two-dimensional (2D) cultures are not capable of modeling this drug delivery barrier in vitro. Thus, tumor spheroids have become increasingly important in cancer research due to their three-dimensional structure. Currently, various methods have been developed to construct tumor spheroids. However, there are still challenges, such as lengthy construction time, complex composition of added growth factors, and high cultivation costs. To address this technical bottleneck, our study combined the GelMA hydrogel system to develop a rapid and high-yield method for tumor spheroids generation. Additionally, we proposed an evaluation scheme to assess the effects of drugs on tumor spheroids. Building on the hyaluronic acid-rich pathological tumor microenvironment, we constructed a resveratrol-loaded nano-drug delivery system with tumor stroma modulation capability and used a three-dimensional (3D) tumor sphere model to simulate in vivo tumor conditions. This process was utilized to completely evaluate the ability of the nano-drug delivery system to enhance the deep penetration of resveratrol in the tumor microenvironment, providing new insights into future oncology drug screening, efficacy assessment, and drug delivery methods.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Congyi Nie,Qian Liang,Qunyu Gao
Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-β-cyclodextrin (HPβCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPβCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability , and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.
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ACS Sustainable Chemistry & Engineering
·
2024
·
IF 7.1
Xingwei Xun,Dongping Chen,Xi-Cun Wang,Xiaofeng Wu,Zheng-Jun Quan
Organic polysulfides have garnered significant attention recently as functional materials due to their abundant S–S bonds and strong chemical bonding structures, with potential applications in heavy metal adsorption, antimicrobials, and lithium–sulfur batteries. However, the environmental concerns associated with petroleum-based polymers and the flammability of sulfur pose challenges for their applications. This study describes the successful preparation of an inverse vulcanization sulfur-rich polymer using biobased resveratrol allyl ether as a copolymerization monomer. The polymer exhibits an ultrahigh glass transition temperature (Tg = 148 °C) and thermal stability, excellent flame retardancy, highly efficient silver absorption (removal rate >99.9%), outstanding silver-regenerative antimicrobial properties (complete inhibition of the growth and propagation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)), as well as excellent specific discharge capacity (1198 mAh g–1), cycling performance, and rate capability. In situ battery infrared and DFT studies indicate that during the electrochemical redox process, the structure of the polymer undergoes a reorganization. The high active sulfur loading electrodes (∼5 mg cm–2) are also prepared to exhibit a certain practical potential with good discharge capacity and capacity retention.
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Journal of Integrative Medicine-JIM
·
2024
·
IF 4.2
Chun-yan Feng,Cheng-song Cai,Xiao-qian Shi,Zhi-juan Zhang,Dan Su,Yun-qing Qiu
Objective Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. Methods HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting analysis were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. Results Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. Conclusion Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis.
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FOOD HYDROCOLLOIDS
·
2019
·
IF 5.839
Xulin Huang,Ye Liu,Yan Zou,Xiao Liang,Yaqi Peng,David Julian McClements,Kun Hu
Zein-pectin core/shell nanoparticles loaded with resveratrol were fabricated using a combination of the antisolvent precipitation and electrostatic deposition methods. These nanoparticles were stable to aggregation from pH 2 to 7 and had good heat stability (80 °C for 1 h). The nanoparticles were exposed to a simulated gastrointestinal tract (GIT) containing stomach and small intestine phases, and their bioaccessibility and antioxidant capacity were then measured. The bioaccessibility of the encapsulated resveratrol was higher than that of free resveratrol. Moreover, the in vitro antioxidant capacity of resveratrol was greatly enhanced when it was encapsulated inside the biopolymer nanoparticles, as shown by more potent ABTS + · radical scavenging and ferric ion reducing power. The gastrointestinal fluids collected after digestion of the encapsulated resveratrol also exhibited strong intracellular reactive oxygen species scavenging activity. Our results suggest that the biopolymer nanoparticles produced in this study may be an effective oral delivery system for resveratrol that could be used in functional foods or nutraceutical supplements.
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BIOMACROMOLECULES
·
2022
·
IF 6.978
Xin-Chuang Wang,Hai-Bo Huang,Wei Gong,Wan-Ying He,Xiang Li,Yu Xu,Xiao-Jie Gong,Jiang-Ning Hu
Programing self-assembly of naturally bioactive molecules has been a wide topic of great significance for biomedical uses. Despite the fact that plant-derived polyphenols with catechol or pyrogallol moieties have been widely studied to construct nanocomplexes or nanocoatings via self-polymerization, there is no report on the self-assembly of these polyphenols into therapeutic hydrogels for potential applications. Here, we reported that adding a very small amount of resveratrol (Res) into the gallic acid (GA) aqueous solution could trigger the quick self-assembly of GA to form a fibrous hydrogel within 5 min through hydrogen bonds and π–π interactions. The length of GA/Res (GR) fibrils in gels varied from 100 to 1000 microns, with a diameter of around 1 μm. Notably, these GR hydrogels showed excellent colloid stability, providing better slow release and outstanding biocompatibility. Also, in vivo experiments indicated the hydrogels had high antibacterial effects and excellent wound healing capabilities in a total skin defect model via regulating the expression of inflammatory factors (IL-6, IL-1β, and TNF-α) due to the release of therapeutic agents (GA and Res) into the matrix. Overall, our results provide a new strategy to accelerate self-assembly of GA by adding Res to form hydrogels, which is further proved as a promising therapeutic carrier for wound healing.
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AAPS PHARMSCITECH
·
2021
·Vol. 22
·期 7
·1-7
·
IF 3.246
Wang Beilei,Shan Xiaoxiao,Lv Shujie,Zha Liqiong,Zhang Caiyun,Dong Qiannian,Chen Weidong
3-O-β-D-galactosylated resveratrol (Gal-Res) was synthesized from resveratrol (Res) and 3-O-β-D-galactose (Gal) in our previous study. In order to improve the pH sensitivity and bioavailability of Gal-Res, Gal-Res nanoparticles (Gal-Res NPs) were prepared using polydopamine (PDA) as a drug carrier. The drug loading (DL %) and entrapment efficiency (EE %) of Gal-Res NPs were 46.80% and 88.06%. The average particle size, polydispersity index (PDI), and Zeta potential of Gal-Res NPs were 179.38 ± 2.83 nm, 0.129 ± 0.013, and − 28.05 ± 0.36 mV, respectively. The transmission electron microscope (TEM) showed that Gal-Res NPs had uniform spherical morphology. Compared with the fast release of raw Gal-Res, the in vitro release of Gal-Res NPs was slow and pH-sensitive. The results of the blood vessel irritation and hemolysis test demonstrated that Gal-Res NPs had good hemocompatibility. The pharmacokinetics study in rats showed that area under the curve of plasma drug concentration time (AUC 0→600 ) and half-life (t 1/2 ) of Gal-Res NPs were enhanced 1.82-fold and 2.19-fold higher than those of raw Gal-Res. The in vivo biodistribution results showed that Gal-Res NPs were more distributed in liver tissue than Gal-Res. Gal-Res NPs with high bioavailability and liver accumulation were hopeful drug delivery systems (DDS) to treat liver diseases. Graphical abstract
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FOOD SCIENCE AND TECHNOLOGY INTERNATIONAL
·
2023
·
IF 2.3
Mingru Wang,Lei Ma,Peng Xie,Cuiping Li,Xiaoxi Yang,Yumiao Lang
The characterization and antioxidant ability of Res-loaded MP-CS stabilized Pickering emulsion, and its effects of fat reduction (25%, 50%, 75%, and 100%) in meat patties on pH, color, texture, cooking yield and antioxidant activity were investigated. Fat substitute using emulsion had no significant effect on pH and cooking yield. The addition of emulsion increased L* value and reduced a* value. a* value of meat patties with resveratrol added were higher than those without resveratrol group. Hardness and chewiness of meat patties with 25% and 100% fat replacement was lower than 50% and 75% fat replacement. The addition of emulsion could improve the network structure of meat patties and enhance oxidative stability. Oxidative stability of meat patties was improved by Res-loaded MP-CS stabilized Pickering emulsion. The results showed that MP-CS stabilized Pickering emulsion had great potential to be used as fat substitute for developing low-fat meat products, and the addition of resveratrol can improve the antioxidant ability of substitute fat meat products.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Wuyang Hua,Yu Cheng,Fenglin Li,Yanhui Li,Zhongkui Lu,Li Li,Dan Wang,Jingxue Liu
Hepatocellular carcinoma remains a fatal disease with a high metastasis risk. Matrix metalloproteinases (MMPs) are key mediators of metastasis and are potential therapeutic targets. Using a natural product derivatization strategy, we designed novel anticancer agents based on resveratrol─a dietary polyphenol found in grapes and other food sources with known MMP-suppressive effects. Although the resveratrol derivative amino-Res (5) showed promising in vitro activity, its poor metabolic stability limited its in vivo efficacy. To address this, we synthesized 14 urea-containing derivatives of amino-Res. Among them, compound 6k exhibited improved metabolic stability and potent anticancer activity both in vitro and in vivo. Mechanism studies revealed that 6k arrests the cell cycle in the G2/M phase, induces intrinsic apoptosis, and inhibits migration and invasion through MMP suppression. This work demonstrates the value of derivatizing dietary natural products for developing novel anticancer agents.
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JOURNAL OF FOOD SAFETY
·
2020
·Vol. 40
·期 3
·e12777
·
IF 1.133
Yingchang Li,Qian Zou,Suzhen Song,Tong Sun,Jianrong Li
The effects of combined application of lysozyme and resveratrol with chitosan coatings on the quality of Sciaenops ocellatus during refrigerated storage were studied. Physical and chemical indices were periodically analyzed. The chitosan composite coatings were characterized, and the mechanical properties and gas permeability were also measured. The results showed that chitosan coatings could significantly reduce the total viable count (TVC), maintain tissue hardness, chewiness and sensory quality, slow the rate of fat oxidation, and restrain the increases in pH and total volatile basic nitrogen (TVB-N). Compared with chitosan coatings, the addition of resveratrol and lysozyme had increased the tensile strength and reduced the gas permeability. The lysozyme–resveratrol–chitosan coatings had good preservation properties. The study indicated that the 0.1% lysozyme + 0.2% resveratrol + 1% chitosan group of composite coatings could maintain the quality and extend the shelf life for 8 days compared with the control group during refrigerated storage.
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BMC Complementary Medicine and Therapies
·
2024
·Vol. 24
·期 1
·1-15
·
IF 3.3
He Yu,Liu Fei,He Mingjuan,Long Fayu,Hu Ding,Chen Jingwen,Fang Miao,Wang Zhenlong
The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.
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