Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array ...Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase(MAPK) and nuclear factor(NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187(PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent(ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin(IL)-6, IL-8, IL-1β, and tumor necrosis factor(TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase(ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.展开更多
Isoquercitrin(IQ)exhibits diverse biological activities,particularly strong antioxidant capacity.However,its poor water solubility and instability limit its widespread application in the food and pharmaceutical indust...Isoquercitrin(IQ)exhibits diverse biological activities,particularly strong antioxidant capacity.However,its poor water solubility and instability limit its widespread application in the food and pharmaceutical industries.To address these challenges,this study encapsulated IQ in gliadin(Gli)and fucoidan(FU)composite nanoparticles(GIF NPs)fabricated via anti-solvent precipitation method.The results showed that hydrophobic interactions promoted the encapsulation of IQ within the hydrophobic core of gliadin nanoparticles(Gli NPs),while FU was adsorbed on the surface of Gli NPs through electrostatic interactions,ultimately forming a multi-layered IQ delivery nanoparticle with good stability.The GIF NPs with a Gli:FU mass ratio of 2:1 possessed a small size(232.87±8.32 nm),appropriate zeta potential(26.22±2.79 mV),and high encapsulation efficiency(78.33±1.87%).The addition of FU not only improved the hydrophilicity of Gli but also enhanced the environmental stability of Gli NPs and their protective effect on IQ.Meanwhile,in vitro simulated digestion studies demonstrated that GIF NPs exhibited good controlled release capability and improved the in vitro bioaccessibility of IQ.These results indicate that Gli/FU nanoparticles could be a potential delivery carrier for hydrophobic bioactive components such as IQ.展开更多
Objective To explore the molecular mechanism by which protein tyrosine phosphatase 1B(PTP1B)enzyme regulates insulin resistance(IR)in diabetes mellitus,and the regulation of isoquercitrin(IS)on PTP1B in vitro and in v...Objective To explore the molecular mechanism by which protein tyrosine phosphatase 1B(PTP1B)enzyme regulates insulin resistance(IR)in diabetes mellitus,and the regulation of isoquercitrin(IS)on PTP1B in vitro and in vivo.Methods In vitro,PTP1B overexpression plasmid was constructed and transiently transfected into human hepatocellular liver carcinoma(HepG2)cells.A co-inducer was prepared by mixing a 0.125 mmol/L palmitic acid solution with a 1.0×10^(-7)mol/L insulin solution to induce IR cell mode.Glucose oxidase assay,quantitative real-time-polymerase chain reaction(qRT-PCR),and Western blot were used to detect the effects of 40µmol/L IS on glucose uptake and mRNA and protein expressions of related factors on the insulin receptor substrate(IRS)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signal pathway in the PTP1B overexpressed IR cell model,respectively.In vivo,PTP1B overexpression adeno-associated virus(Aav-PTP1B)was constructed and injected into the tail vein of mice(200µL/piece).The metabolic indicators of mice were measured after 14-d intragastric administration of IS(40 mg/kg).The pancreas tissue was excised to observe the morphology via hematoxylin-eosin staining.Additionally,qRT-PCR and Western blot assays were performed on the liver tissue of mice to determine the expressions of related factors on the IRS/PI3K/AKT signal pathway of db/db and wild type mice after the intervention of IS on Aav-PTP1B.Results In both in vivo and in vitro experiments,IS significantly improved IR,reduced levels of blood glucose,total cholesterol,triglycerides,and other metabolic indicators in mice,effectively controlled body weight,and restored pancreatic cell morphology(P<0.05 or P<0.01).At the genomic level,IS improved the expressions of related factors in the IRS/PI3K/AKT signaling pathway by regulating the expression of PTP1B(P<0.05 or P<0.01),thereby maintaining the homeostasis of the pathway.Conclusion IS can improve IR by inhibiting the IRS/PI3K/AKT signaling pathway through PTP1B intervention.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
基金Foundation of Beijing Superiority People(D classification,2014000020124G034)
文摘Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase(MAPK) and nuclear factor(NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187(PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent(ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin(IL)-6, IL-8, IL-1β, and tumor necrosis factor(TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase(ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(Grant No.2021A1515110159)the Medical Scientific Research Foundation of Guangdong Province of China(A2024095).
文摘Isoquercitrin(IQ)exhibits diverse biological activities,particularly strong antioxidant capacity.However,its poor water solubility and instability limit its widespread application in the food and pharmaceutical industries.To address these challenges,this study encapsulated IQ in gliadin(Gli)and fucoidan(FU)composite nanoparticles(GIF NPs)fabricated via anti-solvent precipitation method.The results showed that hydrophobic interactions promoted the encapsulation of IQ within the hydrophobic core of gliadin nanoparticles(Gli NPs),while FU was adsorbed on the surface of Gli NPs through electrostatic interactions,ultimately forming a multi-layered IQ delivery nanoparticle with good stability.The GIF NPs with a Gli:FU mass ratio of 2:1 possessed a small size(232.87±8.32 nm),appropriate zeta potential(26.22±2.79 mV),and high encapsulation efficiency(78.33±1.87%).The addition of FU not only improved the hydrophilicity of Gli but also enhanced the environmental stability of Gli NPs and their protective effect on IQ.Meanwhile,in vitro simulated digestion studies demonstrated that GIF NPs exhibited good controlled release capability and improved the in vitro bioaccessibility of IQ.These results indicate that Gli/FU nanoparticles could be a potential delivery carrier for hydrophobic bioactive components such as IQ.
基金Supported by National Natural Science Foundation of China(No.82160701)Guangxi Natural Science Foundation(No.2025GXNSFAA069059)+1 种基金Medical Science Research Fund of Beijing Health Alliance Charitable Foundation(No.KM226002)Guilin Medical University Master’s Research Project(No.GYYK2022004)。
文摘Objective To explore the molecular mechanism by which protein tyrosine phosphatase 1B(PTP1B)enzyme regulates insulin resistance(IR)in diabetes mellitus,and the regulation of isoquercitrin(IS)on PTP1B in vitro and in vivo.Methods In vitro,PTP1B overexpression plasmid was constructed and transiently transfected into human hepatocellular liver carcinoma(HepG2)cells.A co-inducer was prepared by mixing a 0.125 mmol/L palmitic acid solution with a 1.0×10^(-7)mol/L insulin solution to induce IR cell mode.Glucose oxidase assay,quantitative real-time-polymerase chain reaction(qRT-PCR),and Western blot were used to detect the effects of 40µmol/L IS on glucose uptake and mRNA and protein expressions of related factors on the insulin receptor substrate(IRS)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signal pathway in the PTP1B overexpressed IR cell model,respectively.In vivo,PTP1B overexpression adeno-associated virus(Aav-PTP1B)was constructed and injected into the tail vein of mice(200µL/piece).The metabolic indicators of mice were measured after 14-d intragastric administration of IS(40 mg/kg).The pancreas tissue was excised to observe the morphology via hematoxylin-eosin staining.Additionally,qRT-PCR and Western blot assays were performed on the liver tissue of mice to determine the expressions of related factors on the IRS/PI3K/AKT signal pathway of db/db and wild type mice after the intervention of IS on Aav-PTP1B.Results In both in vivo and in vitro experiments,IS significantly improved IR,reduced levels of blood glucose,total cholesterol,triglycerides,and other metabolic indicators in mice,effectively controlled body weight,and restored pancreatic cell morphology(P<0.05 or P<0.01).At the genomic level,IS improved the expressions of related factors in the IRS/PI3K/AKT signaling pathway by regulating the expression of PTP1B(P<0.05 or P<0.01),thereby maintaining the homeostasis of the pathway.Conclusion IS can improve IR by inhibiting the IRS/PI3K/AKT signaling pathway through PTP1B intervention.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
