Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer...Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.展开更多
Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here...Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)reuptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antidepressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protection,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor receptor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.展开更多
Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger i...Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger individuals.Luteolin,a common flavonoid compound,exhibits multiple biological effects,including inhibition of tumor proliferation and inflammatory responses.It also suppresses the activity of urate transporter 1(URAT1),promoting uric acid excretion.This study is the first to integrate network toxicology and network pharmacology approaches to systematically analyze the multi-target mechanisms of adenine-induced HUA and luteolin-treated HUA,with molecular docking validation of interaction targets.We constructed compound-pathway-intersection gene networks and a dual-group PPI network to analyze the mechanisms of adenine-induced HUA and luteolin-treated HUA.The dual-group PPI network identified 7 shared targets,namely XDH,PYGL,IL10,PPARG,TNF,VEGFA,and MAOA,involving core intersecting pathways such as purine-xanthine metabolism and insulin resistance.Luteolin may activate PPARG to regulate inflammation and uric acid excretion modules in the adenine network.GO-KEGG analysis indicates that intersection genes for adenine pathogenesis involve diverse biological processes,cellular components,and molecular functions,with core target KEGG analysis revealing 15 signaling pathways.Luteolin’s therapeutic targets are associated with more entries,and its core target KEGG analysis identified 46 signaling pathways.Molecular docking shows TNF,PPARG,and PYGL bind to both luteolin and adenine with negative binding energies,and luteolin’s binding energies are all below 5 kJ/mol,confirming stable binding.Luteolin’s anti-HUA mechanism is characterized by inhibition of production,promotion of excretion,anti-inflammation and metabolic regulation,but interactions with gut microbiota metabolites require further study.展开更多
During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many...During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.展开更多
This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through mic...This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through micro-flotation testing.At pH=9,with LUT concentration of 50 mg·L^(-1) and NaOL concentration of 50 mg·L^(-1),scheelite recovery reaches 80.3%.Calcite,on the other hand,exhibits a recovery rate of 17.6%,indicating a significant difference in floatability between the two minerals.Subsequently,the surface modifica-tions of scheelite and calcite following LUT treatment are characterized using adsorption capacity testing,Zeta potential analysis,Fourier transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),and atomic force microscopy(AFM).The study in-vestigates the selective depressant mechanism of LUT on calcite.Adsorption capacity testing and Zeta potential analysis demonstrate sub-stantial absorption of LUT on the surface of calcite,impeding the further adsorption of sodium oleate,while its impact on scheelite is min-imal.FT-IR and XPS analyses reveal the selective adsorption of LUT onto the surface of calcite,forming strong chemisorption bonds between the hydroxyl group and calcium ions present.AFM directly illustrates the distinct adsorption densities of LUT on the two miner-al types.Consequently,LUT can effectively serve as a depressant for calcite,enabling the successful separation of scheelite and calcite.展开更多
The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and ...The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2%DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol^(-1 )in mouse,respectively;the affinity of luteolin for Notch1 and RBPJ was respectively scored to be-6.4 kcal·mol^(-1) and-7.7 kcal·mol^(-1) homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.展开更多
Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods...Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species elevation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-a demonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.Please cite this article as:Zhai P,Ouyang XH,Yang ML,Lin L,Li JY,Li YM,Cheng X,Zhu R,Hu DS.Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.J Integr Med.2024;22(6):652–664.展开更多
Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Lut...Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.展开更多
Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuropro...Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.展开更多
Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its str...Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.展开更多
基金the financial support from Henan Province Natural Science Foundation(No.252300420583)Henan Provincial Science and Technology Research Project(Nos.242102310455,242102310473,242102310517)the Key Project of Science and Technology Research funded by the Henan Provincial Department of Education(No.24A350002)。
文摘Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.
基金supporting by the National Nature Science Foundation of China(Grant No.:82071215)the Outstanding Scientific Fund of Shengjing Hospital,China(Grant No.:202208).
文摘Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)reuptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antidepressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protection,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor receptor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.
基金supported by the National College Student Innovation and Entrepreneurship Project.
文摘Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger individuals.Luteolin,a common flavonoid compound,exhibits multiple biological effects,including inhibition of tumor proliferation and inflammatory responses.It also suppresses the activity of urate transporter 1(URAT1),promoting uric acid excretion.This study is the first to integrate network toxicology and network pharmacology approaches to systematically analyze the multi-target mechanisms of adenine-induced HUA and luteolin-treated HUA,with molecular docking validation of interaction targets.We constructed compound-pathway-intersection gene networks and a dual-group PPI network to analyze the mechanisms of adenine-induced HUA and luteolin-treated HUA.The dual-group PPI network identified 7 shared targets,namely XDH,PYGL,IL10,PPARG,TNF,VEGFA,and MAOA,involving core intersecting pathways such as purine-xanthine metabolism and insulin resistance.Luteolin may activate PPARG to regulate inflammation and uric acid excretion modules in the adenine network.GO-KEGG analysis indicates that intersection genes for adenine pathogenesis involve diverse biological processes,cellular components,and molecular functions,with core target KEGG analysis revealing 15 signaling pathways.Luteolin’s therapeutic targets are associated with more entries,and its core target KEGG analysis identified 46 signaling pathways.Molecular docking shows TNF,PPARG,and PYGL bind to both luteolin and adenine with negative binding energies,and luteolin’s binding energies are all below 5 kJ/mol,confirming stable binding.Luteolin’s anti-HUA mechanism is characterized by inhibition of production,promotion of excretion,anti-inflammation and metabolic regulation,but interactions with gut microbiota metabolites require further study.
文摘During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.
基金supported by the National Natural Science Foundation of China (No.52164022).
文摘This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through micro-flotation testing.At pH=9,with LUT concentration of 50 mg·L^(-1) and NaOL concentration of 50 mg·L^(-1),scheelite recovery reaches 80.3%.Calcite,on the other hand,exhibits a recovery rate of 17.6%,indicating a significant difference in floatability between the two minerals.Subsequently,the surface modifica-tions of scheelite and calcite following LUT treatment are characterized using adsorption capacity testing,Zeta potential analysis,Fourier transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),and atomic force microscopy(AFM).The study in-vestigates the selective depressant mechanism of LUT on calcite.Adsorption capacity testing and Zeta potential analysis demonstrate sub-stantial absorption of LUT on the surface of calcite,impeding the further adsorption of sodium oleate,while its impact on scheelite is min-imal.FT-IR and XPS analyses reveal the selective adsorption of LUT onto the surface of calcite,forming strong chemisorption bonds between the hydroxyl group and calcium ions present.AFM directly illustrates the distinct adsorption densities of LUT on the two miner-al types.Consequently,LUT can effectively serve as a depressant for calcite,enabling the successful separation of scheelite and calcite.
基金supported by the National Natural Science Foundation of China(No.82074092)the Natural Science Foundation of Guangdong Province(No.2021A1515012219)Guangzhou University of Chinese Medicine“Double First-Class”and High-level University Discipline Collaborative Innovation Team Project(No.2021xk81).
文摘The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2%DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol^(-1 )in mouse,respectively;the affinity of luteolin for Notch1 and RBPJ was respectively scored to be-6.4 kcal·mol^(-1) and-7.7 kcal·mol^(-1) homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.
基金financially supported by grants from the National Natural Science Foundation of China(No.82104488,81974249,82274317,and 82161138003)。
文摘Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species elevation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-a demonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.Please cite this article as:Zhai P,Ouyang XH,Yang ML,Lin L,Li JY,Li YM,Cheng X,Zhu R,Hu DS.Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.J Integr Med.2024;22(6):652–664.
基金supported by the Korea Research Institute of Bioscience and Biotechnology(KRIBB)Research Initiative Program(KGM4252331,KGM5382322),Republic of Korea.
文摘Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yang YXAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Lu QX.
文摘Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.
文摘Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.
