RESUMEN
Photodynamic inactivation is an emerging antimicrobial treatment that can be enhanced by employing exogenous photosensitizers to eradicate foodborne pathogens. This study investigated a novel combinatory strategy to eradicate Listeria monocytogenes using blackthorn fruit peel (BFP) and blue light (BL). Extracts of BFP were characterized in terms of polyphenolic content, individual constituents, and antioxidant and antimicrobial activity. The concentration of phenolic compounds and antioxidant activity were both found to be determinants of antimicrobial activity. It was further speculated that flavonols, predominantly quercetin and rutin, were responsible for the activity of BFP against L. monocytogenes. A combination of BFP and BL resulted in a rapid inactivation of the pathogen by up to 4 log CFU/mL at 58.5 J/cm2, corresponding to 15 min BL illumination. Flow cytometry analysis revealed that the bacterial cells lost activity and suffered extensive membrane damage, exceeding 90% of the population. After photosensitizing L. monocytogenes with the BFP constituents quercetin and rutin, a 1.3-log reduction was observed. When applied together, these compounds could inflict the same damaging effect on cells as they did individually when effects were added. Therefore, the results indicate that BFP represents a natural source of (pro-)photosensitizers, which act additively to create inactivation effects. This study may help identify more effective plant-based photosensitizers to control L. monocytogenes in food-related applications.
Asunto(s)
Frutas , Luz , Listeria monocytogenes , Fármacos Fotosensibilizantes , Extractos Vegetales , Polifenoles , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/efectos de la radiación , Listeria monocytogenes/crecimiento & desarrollo , Polifenoles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Frutas/química , Frutas/microbiología , Fármacos Fotosensibilizantes/farmacología , Crataegus/química , Antibacterianos/farmacología , Antioxidantes/farmacología , Quercetina/farmacología , Viabilidad Microbiana/efectos de los fármacos , Viabilidad Microbiana/efectos de la radiación , Luz AzulRESUMEN
Purpose: To investigate the renal pathophysiological processes and protective effect of quercetin on contrast-induced acute kidney injury (CI-AKI) in mice with type 1 diabetic mellitus(DM) using diffusion tensor imaging(DTI).Methods: Mice with DM were divided into two groups. In the diabetic + contrast medium(DCA) group, the changes of the mice kidneys were monitored at 1, 24, 48, and 72 h after the injection of iodixanol(4gI/kg). The mice in the diabetic + contrast medium + quercetin(DCA + QE) group were orally given different concentrations of quercetin for seven days before injection of iodixanol. In vitro experiments, renal tubular epithelial (HK-2) cells exposed to high glucose conditions were treated with various quercetin concentrations before treatment with iodixanol(250â mgI/mL).Results: DTI-derived mean diffusivity(MD) and fractional anisotropy(FA) values can be used to evaluate CI-AKI effectively. Quercetin significantly increased the expression of Sirt 1 and reduced oxidative stress by increasing Nrf 2/HO-1/SOD1. The antiapoptotic effect of quercetin on CI-AKI was revealed by decreasing proteins level and by reducing the number of apoptosis-positive cells. In addition, flow cytometry indicated quercetin-mediated inhibition of M1 macrophage polarization in the CI-AKI.Conclusions: DTI will be an effective noninvasive tool in diagnosing CI-AKI. Quercetin attenuates CI-AKI on the basis of DM through anti-oxidative stress, apoptosis, and inflammation.
Asunto(s)
Lesión Renal Aguda , Medios de Contraste , Diabetes Mellitus Tipo 1 , Imagen de Difusión Tensora , Quercetina , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/diagnóstico por imagen , Medios de Contraste/efectos adversos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/complicaciones , Masculino , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Riñón/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ácidos TriyodobenzoicosRESUMEN
Objective: The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)-like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. Methods: A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results: Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme-linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin-eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and Aß protein accumulation in AD mice. Western blot validated protein expression in the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO-1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO-1, caspase-3, Bcl-2, and Bax proteins in the Keap1/Nrf2/HO-1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Conclusion: Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.
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Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Apoptosis , Encéfalo , Disfunción Cognitiva , Modelos Animales de Enfermedad , Hemo-Oxigenasa 1 , Proteína 1 Asociada A ECH Tipo Kelch , Ratones Transgénicos , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Quercetina , Animales , Quercetina/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo/efectos de los fármacos , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Hemo-Oxigenasa 1/metabolismo , Apoptosis/efectos de los fármacos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Transducción de Señal/efectos de los fármacos , Presenilina-1/genética , Presenilina-1/metabolismo , Masculino , Ratones Endogámicos C57BL , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Antioxidantes/farmacología , Antioxidantes/metabolismoRESUMEN
Sarmentosin (SA) and Quercetin (QC) are two active components of Sedum Sarmentosum Bunge, which is a traditional Chinese herbal medicine. This study aimed to investigate the role and regulatory mechanism of SA and QC in fatty liver of Genetic Improvement of Farmed Tilapia (GIFT) tilapia. GIFT tilapia were randomly divided into two groups with three replicates per treatment (30 fish in each replicate): normal diet group (average weight 3.51±0.31 g) and high-fat diet group (average weight 3.44±0.09 g). After 8 weeks feeding trial, growth index, lipid deposition, and biochemical indexes were measured. Lipid deposition, and lipid and inflammation-related gene expression were detected in a primary hepatocyte model of fatty liver of GIFT tilapia treated with SA or QC. Our results showed that high-fat diet caused lipid deposition and peroxidative damage in the liver of GIFT tilapia. The cell counting kit-8 assay results indicated that 10 µM SA and 10 µM of QC both had the least effect on hepatocyte proliferation. Moreover, both 10 µM of SA and 10 µM of QC showed lipolytic effects and inhibited the expression of lipid-related genes (FAS, Leptin, SREBP-1c, and SREBP2) in fatty liver cells. Interestingly, QC induced autophagosome-like subcellular structure and increased the expression of IL-8 in fatty liver cells. In conclusion, this study confirmed that SA and QC improved fatty liver caused by high-fat diet, providing a novel therapeutic approach for fatty liver of GIFT tilapia.
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Hígado Graso , Hepatocitos , Metabolismo de los Lípidos , Quercetina , Animales , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Quercetina/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Cíclidos/metabolismo , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Tilapia/metabolismo , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/tratamiento farmacológico , Proliferación Celular/efectos de los fármacosRESUMEN
Difenoconazole (DIF) is frequently used for the management of fungal infections in fruit and vegetables and excessive residues in the aquatic environment can have adverse effects on fish such as growth inhibition. A treatment based on the dietary additive quercetin (QUE) is a promising approach to positively regulate the state of fish growth. This study focused on whether and how QUE alleviated DIF-induced growth inhibition in fish. In this study, carp were exposed to DIF (0.3906 mg/L) for consecutive 30 d, which showed growth inhibition. Disruption of the intestinal barrier led to elevated levels of intestinal lipopolysaccharide (LPS) and an inflammatory response. Through the intestinal-brain axis, LPS entered the brain where it disrupted the blood-brain barrier, triggered neuroinflammation, caused brain cell apoptosis, and damaged nerves in addition to other things. The dietary supplementation of QUE (400 mg/kg) reduced the levels of LPS in the intestinal and brain, while reducing inflammation and increasing the expression of appetite factors, thereby reducing growth inhibition in carp. This work provided evidence for QUE from the intestinal-brain axis perspective as a potential candidate for alleviating growth inhibition in fish.
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Encéfalo , Carpas , Dioxolanos , Intestinos , Quercetina , Animales , Carpas/metabolismo , Quercetina/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Intestinos/efectos de los fármacos , Dioxolanos/farmacología , Triazoles/farmacología , Lipopolisacáridos/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Fungicidas Industriales/farmacologíaRESUMEN
Neutrophil extracellular traps (NETs) are three-dimensional reticular structures that release chromatin and cellular contents extracellularly upon neutrophil activation. As a novel effector mechanism of neutrophils, NETs possess the capacity to amplify localized inflammation and have been demonstrated to contribute to the exacerbation of various inflammatory diseases, including cardiovascular diseases and tumors. It is suggested that lysophosphatidylcholine (LPC), as the primary active component of oxidized low-density lipoprotein, represents a significant risk factor for various inflammatory diseases, such as cardiovascular diseases and neurodegenerative diseases. However, the specific mechanism of NETs formation induced by LPC remains unclear. Quercetin has garnered considerable attention due to its anti-inflammatory properties, serving as a prevalent flavonoid in daily diet. However, little is currently known about the underlying mechanisms by which quercetin inhibits NETs formation and alleviates associated diseases. In our study, we utilized LPC-treated primary rat neutrophils to establish an in vitro model of NETs formation, which was subsequently subjected to treatment with a combination of quercetin or relevant inhibitors/activators. Compared to the control group, the markers of NETs and the expression of P2X7R/P38MAPK/NOX2 pathway-associated proteins were significantly increased in cells treated with LPC alone. Quercetin intervention decreased the LPC-induced upregulation of the P2X7R/P38MAPK/NOX2 pathway and effectively reduced the expression of NETs markers. The results obtained using a P2X7R antagonist/activator and P38MAPK inhibitor/activator support these findings. In summary, quercetin reversed the upregulation of the LPC-induced P2X7R/P38MAPK/NOX2 pathway, further mitigating NETs formation. Our study investigated the potential mechanism of LPC-induced NETs formation, elucidated the inhibitory effect of quercetin on NETs formation, and offered new insights into the anti-inflammatory properties of quercetin.
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Trampas Extracelulares , Lisofosfatidilcolinas , NADPH Oxidasa 2 , Neutrófilos , Quercetina , Receptores Purinérgicos P2X7 , Proteínas Quinasas p38 Activadas por Mitógenos , Quercetina/farmacología , Lisofosfatidilcolinas/metabolismo , Lisofosfatidilcolinas/farmacología , Trampas Extracelulares/metabolismo , Trampas Extracelulares/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Ratas , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Receptores Purinérgicos P2X7/metabolismo , NADPH Oxidasa 2/metabolismo , Transducción de Señal/efectos de los fármacos , MasculinoRESUMEN
Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1ß, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. In vivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.
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Condrocitos , Factor 2 Relacionado con NF-E2 , FN-kappa B , Osteoartritis , Quercetina , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Proteína ADAMTS5/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Ciclooxigenasa 2/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Osteoartritis/patología , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/química , Quercetina/uso terapéutico , Transducción de Señal/efectos de los fármacosRESUMEN
The present study deals with the in-silico analyses of several flavonoid derivatives to explore COVID-19 through pharmacophore modelling, molecular docking, molecular dynamics, drug-likeness, and ADME properties. The initial literature study revealed that many flavonoids, including luteolin, quercetin, kaempferol, and baicalin may be useful against SARS ß-coronaviruses, prompting the selection of their potential derivatives to investigate their abilities as inhibitors of COVID-19. The findings were streamlined using in silico molecular docking, which revealed promising energy-binding interactions between all flavonoid derivatives and the targeted protein. Notably, compounds 8, 9, 13, and 15 demonstrated higher potency against the coronavirus Mpro protein (PDB ID 6M2N). Compound 8 has a -7.2 Kcal/mol affinity for the protein and binds to it by hydrogen bonding with Gln192 and π-sulfur bonding with Met-165. Compound 9 exhibited a significant interaction with the main protease, demonstrating an affinity of -7.9 kcal/mol. Gln-192, Glu-189, Pro-168, and His-41 were the principle amino acid residues involved in this interaction. The docking score for compound 13 is -7.5 Kcal/mol, and it binds to the protease enzyme by making interactions with Leu-41, π-sigma, and Gln-189. These interactions include hydrogen bonding and π-sulfur. The major protease and compound 15 were found to bind with a favourable affinity of -6.8 Kcal/mol. This finding was further validated through molecular dynamic simulation for 1ns, analysing parameters such as RMSD, RMSF, and RoG profiles. The RoG values for all four of the compounds varied significantly (35.2-36.4). The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADME and drug-likeness properties, fulfilling all the necessary criteria. The findings of the study may support further efforts for the discovery and development of safe drugs to treat COVID-19.
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Antivirales , Proteasas 3C de Coronavirus , Diseño de Fármacos , Flavonoides , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , SARS-CoV-2 , Flavonoides/química , Flavonoides/farmacología , Antivirales/farmacología , Antivirales/química , SARS-CoV-2/efectos de los fármacos , Humanos , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/metabolismo , COVID-19/virología , Descubrimiento de Drogas/métodos , Enlace de Hidrógeno , Tratamiento Farmacológico de COVID-19 , Betacoronavirus/efectos de los fármacos , Pandemias , Quercetina/química , Quercetina/farmacología , Unión Proteica , Proteínas M de CoronavirusRESUMEN
Cytokine storm (CS) emerges as an exacerbated inflammatory response triggered by various factors such as pathogens and excessive immunotherapy, posing a significant threat to life if left unchecked. Quercetin, a monomer found in traditional Chinese medicine, exhibits notable anti-inflammatory and antiviral properties. This study endeavors to explore whether quercetin intervention could mitigate CS through a combination of network pharmacology analysis and experimental validation. First, common target genes and potential mechanisms affected by quercetin and CS were identified through network pharmacology, and molecular docking experiments confirmed quercetin and core targets. Subsequently, in vitro experiments of Raw264.7 cells stimulated by lipopolysaccharide (LPS) showed that quercetin could effectively inhibit the overexpression of pro-inflammatory mediators and regulate the AKT1-FoxO1 signaling pathway. At the same time, quercetin can reduce ROS through the Keap1-Nrf2 signaling pathway. In addition, in vivo studies of C57BL/6 mice injected with LPS further confirmed quercetin's inhibitory effect on CS. In conclusion, this investigation elucidated novel target genes and signaling pathways implicated in the therapeutic effects of quercetin on CS. Moreover, it provided compelling evidence supporting the efficacy of quercetin in reversing LPS-induced CS, primarily through the regulation of the AKT1-FoxO1 and Keap1-Nrf2 signaling pathways.
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Proteína Forkhead Box O1 , Proteína 1 Asociada A ECH Tipo Kelch , Lipopolisacáridos , Macrófagos , Factor 2 Relacionado con NF-E2 , Proteínas Proto-Oncogénicas c-akt , Quercetina , Transducción de Señal , Quercetina/farmacología , Animales , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína Forkhead Box O1/metabolismo , Células RAW 264.7 , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/metabolismo , Síndrome de Liberación de Citoquinas/prevención & control , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.
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Analgésicos , Neuropatías Diabéticas , Formaldehído , Quercetina , Animales , Ratones , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/inducido químicamente , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Modelos Animales de Enfermedad , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Yohimbina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Naloxona/farmacología , Naloxona/uso terapéutico , Estreptozocina , Dimensión del Dolor/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
Objectives: The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. Methods: Mice received intranasal Aß1-42 (5 µg/10 µL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg-1 and 100 mg kg-1 doses for one week starting from day five following Aß1-42 peptide administration. Following this, the animals were evaluated for neurobehavioral parameters using a Morris water maze test and a novel object recognition test. Further to this, the biomarkers for neuroinflammation and neurodegeneration were evaluated in the hippocampus and cortex regions of the brain in these animals. Results: Multiple exposures to intranasal Aß led to a significant decline in the learning and cognitive memory of the animals, whereas oral treatment with quercetin at dosages of 30 and 100 mg kg-1 alleviated Aß-induced effects. Quercetin treatment significantly reduced Aß accumulation, oxidative stress and proinflammatory cytokine biomarkers in the brain. In addition, it also alleviated the activation of astrocytic biomarkers, amyloid precursor protein and phosphorylated-tau proteins in the brain. Conclusion: Quercetin was found to be a potent antioxidant, anti-inflammatory compound with protection against neurodegenerative damage and improved learning and cognitive memory in a repeated Aß-exposure model of AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Encéfalo , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias , Quercetina , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Quercetina/farmacología , Quercetina/administración & dosificación , Ratones , Péptidos beta-Amiloides/metabolismo , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Administración Intranasal , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , HumanosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Every year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. AIM OF THE STUDY: This study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. MATERIALS AND METHODS: Bioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. RESULTS: QC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 µM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 µM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). CONCLUSION: Effective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.
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Anticoagulantes , Fibrinolíticos , Extractos Vegetales , Agregación Plaquetaria , Quercetina , Solanum , Animales , Quercetina/farmacología , Quercetina/aislamiento & purificación , Ratones , Fibrinolíticos/farmacología , Fibrinolíticos/aislamiento & purificación , Solanum/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Anticoagulantes/farmacología , Anticoagulantes/aislamiento & purificación , Humanos , Agregación Plaquetaria/efectos de los fármacos , Masculino , Plantas Medicinales/química , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Frutas/química , Trombina , Simulación del Acoplamiento Molecular , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Coagulación Sanguínea/efectos de los fármacosRESUMEN
Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of Qc. The developed alginate-modified quercetin-loaded ZIF-8 (Alg@Qc@ZIF-8) was characterized using scanning electron microscope (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy Thermogravimetric analysis, Brunauer-Emmett-Teller, and x-ray diffraction. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, -23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02%. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more Qc at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 h. Furthermore, the IC50value of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net Qc. Considering thein vitroandin vivooutcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management.
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Alginatos , Antineoplásicos , Estructuras Metalorgánicas , Nanocompuestos , Quercetina , Quercetina/farmacología , Quercetina/química , Animales , Nanocompuestos/química , Alginatos/química , Alginatos/farmacología , Ratones , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Femenino , Ratones Endogámicos BALB C , Liberación de Fármacos , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Humanos , ImidazolesRESUMEN
Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 µM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.
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Supervivencia Celular , Fumonisinas , Quercetina , Especies Reactivas de Oxígeno , Células de Sertoli , Quercetina/farmacología , Fumonisinas/toxicidad , Masculino , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Ratones , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Glucólisis/efectos de los fármacos , Sustancias Protectoras/farmacologíaRESUMEN
It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection.
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Acetaldehído , Antioxidantes , Glutatión , Hemo-Oxigenasa 1 , Hepatocitos , Quercetina , Especies Reactivas de Oxígeno , Acetaldehído/toxicidad , Acetaldehído/farmacología , Quercetina/farmacología , Animales , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Ratones , Hemo-Oxigenasa 1/metabolismo , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Línea Celular Tumoral , Glutamato-Cisteína Ligasa/metabolismo , Glutamato-Cisteína Ligasa/genéticaRESUMEN
BACKGROUND: Taxifolin (TAX), a flavonoid abundant in various medicinal plants, has gained attention for its multifaceted role in cancer therapy and cytoprotection against chemotherapy-induced toxicities. TAX modulates key signaling pathways to regulate several processes within tumors, thus potentially playing an important role in tumor suppression. PURPOSE: This review aims to explore the current understanding of TAX's role in cancer therapy including its antitumor mechanisms, synergistic combinations, and cytoprotective effects. The review also addresses the safety profile of TAX, highlights its pharmacokinetic (PK) properties limiting its use, and summarizes the suggested pharmaceutical and chemical solutions to overcome these limitations. METHODOLOGY: A literature review was conducted through searching online databases such as PubMed and Google Scholar using several combinations of relevant keywords related to TAX's potential in anticancer therapy. A total of 84 articles published within the last 15 years were included in this review and analyzed following the PRISMA guidelines. RESULTS: TAX inhibits tumor proliferation, migration, and invasion via the cGMP-PKG pathway, inducing G1-phase arrest and apoptosis. TAX's anti-angiogenic and pro-apoptotic effects are mediated by downregulating Hif1-α, VEGF, and AKT. Additionally, it can synergize the conventional chemotherapeutic agents, enhancing their efficacy and mitigating drug resistance by inhibiting P-glycoprotein expression. Additionally, TAX demonstrates cytoprotective effects against cisplatin-induced nephrotoxicity and neurotoxicity, cyclophosphamide/pazopanib-induced hepatotoxicity, methotrexate-induced oral mucositis, and doxorubicin-induced cardiotoxicity by inhibiting ferroptosis. TAX further has immunomodulatory effects in the tumor microenvironment, enhancing immune responses and sensitizing tumors to immune checkpoint inhibitors. Advancements in TAX's anticancer effects include introducing novel drug delivery systems and chemical modifications to generate derivatives with improved pharmacological effects. CONCLUSION: Clinical trials are needed to confirm TAX's safety and effectiveness in cancer therapy, optimize formulations, and investigate synergistic combinations. Overall, TAX holds promise as a versatile anticancer agent, offering direct anticancer effects and protective benefits against chemotherapy-induced toxicities.
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Sinergismo Farmacológico , Neoplasias , Quercetina , Humanos , Quercetina/farmacología , Quercetina/análogos & derivados , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Mycoplasma gallisepticum (MG) has long been a pathogenic microorganism threatening the global poultry industry. Previous studies have demonstrated that the mechanism by which quercetin (QUE) inhibits the colonization of MG in chicks differs from that of antibiotics. However, the molecular mechanism by which QUE facilitates the clearance of MG remains unclear. PURPOSE: The aim of this study was to investigate the molecular mechanism of MG clearance by QUE, with the expectation of providing new options for the treatment of MG. METHODS: A model of MG infection in chicks and MG-induced M1 polarization in HD-11 cells were established. The mechanism of QUE clearance of MG was investigated by evaluating the relationship between tracheal mucosal barrier integrity, antibody levels, Th1/Th2 immune balance and macrophage metabolism and M1/M2 polarization balance. Furthermore, network pharmacology and molecular docking techniques were employed to explore the potential molecular pathways connecting QUE, M2 polarization, and fatty acid oxidation (FAO). RESULTS: The findings indicate that QUE remodels tracheal mucosal barrier function by regulating tight junctions and secretory immunoglobulin A (sIgA) expression levels. This process entails the regulatory function of QUE on the Th1/Th2 immune imbalance that is induced by MG infection in the tracheal mucosa. Moreover, QUE intervention impeded the M1 polarization of HD-11 cells induced by MG infection, while simultaneously promoting M2 polarization through the induction of FAO. Conversely, inhibitors of the FAO pathway impede this effect. The results of computer network analysis suggest that QUE may induce FAO via the PI3K/AKT pathway to promote M2 polarization. Notably, inhibition of the PI3K/AKT pathway was found to effectively inhibit M2 polarization in HD-11 cells, while having a limited effect on FAO. CONCLUSIONS: QUE promotes M2 polarization of HD-11 cells to enhance Th2 immune response through FAO and PI3K/AKT pathways, thereby restoring tracheal mucosal barrier function and ultimately inhibiting MG colonization.
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Pollos , Infecciones por Mycoplasma , Mycoplasma gallisepticum , Enfermedades de las Aves de Corral , Quercetina , Células Th2 , Animales , Quercetina/farmacología , Mycoplasma gallisepticum/efectos de los fármacos , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/inmunología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Tráquea/efectos de los fármacos , Simulación del Acoplamiento Molecular , Uniones Estrechas/efectos de los fármacos , Inmunoglobulina A Secretora/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células TH1/efectos de los fármacos , Células TH1/inmunología , Macrófagos/efectos de los fármacos , Ácidos GrasosRESUMEN
BACKGROUND: Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented. Specifically, shed endometrial tissues (delivered to the pelvic cavity via retrograde menstruation) reveal that a subset of stromal cells exhibiting pro-inflammatory, pro-fibrotic, and pro-senescence-like phenotypes is enhanced in endometriosis patients compared to controls. Additionally, cultured biopsy-derived endometrial stromal cells from endometriosis patients exhibit impaired decidualization, a defined differentiation process required for human embryo implantation and pregnancy. Quercetin, a senolytic agent, shows therapeutic potential for pulmonary fibrosis, a disorder attributed to senescent pulmonary fibroblasts. In rodent models of endometriosis, quercetin shows promise, and quercetin improves decidualization in vitro. However, the exact mechanisms are not completely understood. Therefore, we investigated the effects of quercetin on menstrual effluent-derived endometrial stromal cells from endometriosis patients and unaffected controls to define the signaling pathways underlying quercetin's effects on endometrial stromal cells. METHODS: Menstrual effluent-derived endometrial stromal cells were collected and cultured from unaffected controls and endometriosis patients and then, low passage cells were treated with quercetin (25 µM) under basal or standard decidualization conditions. Decidualization responses were analyzed by measuring the production of IGFBP1 and PRL. Also, the effects of quercetin on intracellular cAMP levels and cellular oxidative stress responses were measured. Phosphokinase arrays, western blotting, and flow cytometry methods were performed to define the effects of quercetin on various signaling pathways and the potential mechanistic roles of quercetin. RESULTS: Quercetin significantly promotes decidualization of control- and endometriosis-endometrial stromal cells. Quercetin substantially reduces the phosphorylation of multiple signaling molecules in the AKT and ERK1/2 pathways, while enhancing the phosphorylation of p53 and total p53 levels. Furthermore, p53 inhibition blocks decidualization while p53 activation promotes decidualization. Finally, we provide evidence that quercetin increases apoptosis of endometrial stromal cells with a senescent-like phenotype. CONCLUSIONS: These data provide insight into the mechanisms of action of quercetin on endometrial stromal cells and warrant future clinical trials to test quercetin and other senolytics for treating endometriosis.
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Senescencia Celular , Endometriosis , Proteínas Proto-Oncogénicas c-akt , Quercetina , Células del Estroma , Proteína p53 Supresora de Tumor , Quercetina/farmacología , Femenino , Humanos , Endometriosis/metabolismo , Endometriosis/patología , Endometriosis/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adulto , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Senescencia Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Decidua/efectos de los fármacos , Decidua/metabolismo , Transducción de Señal/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células CultivadasRESUMEN
BACKGROUND: Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. METHODS AND RESULTS: DM was induced in eighteen rats through intraperitoneal injections of 50 mg/kg streptozotocin and 110 mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50 mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. CONCLUSIONS: TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50 mg/kg TXF was more effective than 25 mg/kg and is recommended for consumption.
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Apoptosis , Caspasa 3 , Diabetes Mellitus Experimental , Hígado , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-bcl-2 , Quercetina , Transducción de Señal , Proteína X Asociada a bcl-2 , Animales , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Transducción de Señal/efectos de los fármacos , Masculino , Caspasa 3/metabolismo , Caspasa 3/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Apoptosis/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Insulina/metabolismoRESUMEN
Styphnolobium japonicum leaves are considered a rich source of flavonoids, which are the prospective basis for various therapeutic effects. However, there has been a lack of comprehensive cytotoxic studies conducted on these leaves. Therefore, this ongoing investigation aimed to detect and isolate the flavonoids present in S. japonicum leaves, and assess their antioxidant and anticancer properties. The defatted extract from S. japonicum leaves was analyzed using HPLC, which resulted in the identification of seven phenolics and six flavonoids. Rutin and quercetin were found to be the most abundant. Furthermore, a comprehensive profile of flavonoids was obtained through UPLC/ESI-MS analysis in negative acquisition mode. Fragmentation pathways of the identified flavonoids were elucidated to gain relevant insights into their structural characteristics. Furthermore, genistein 7-O-glucoside, quercetin 3-O-rutinoside, and kaempferol 3-O-α-L-rhamnopyranosyl-(1 â 6)-ß-D-glucopyranosyl-(1 â 2)-ß-D-glucopyranoside were isolated and characterized. The defatted extract rich in flavonoids exhibited significant antioxidant, iron-reducing, free radicals scavenging impacts, and remarkable cytotoxicity against the liver cell line (IC50 337.9µg/ mL) and lung cell line (IC50 55.0 µg/mL). Furthermore, the antioxidant and anticancer capacities of the three isolated flavonoids have been evaluated, and it has been observed that their effects are concentration-dependent. The findings of this research highlight the promising impact of flavonoids in cancer therapy. It is recommended that future scientific investigations prioritize the exploration of the distinct protective and therapeutic characteristics of S. japonicum leaves, which hold significant potential as a valuable natural resource.