RESUMEN
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.
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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
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
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
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
This study explored the mechanism of Huangbai liniment (HB) for the treatment of oral lichen planus (OLP) through network pharmacology and molecular docking techniques. The study identified HB' active ingredients, therapeutic targets for OLP, and associated signaling pathways. The chemical composition of HB was screened using the HERB database. The disease targets of OLP were obtained through the GeneCards and OMIM databases. A protein-protein interactions network was constructed with the String platform. Topological analysis was performed using Cytoscape software to identify core targets. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the Hiplot database, and the active ingredients and core targets were verified by molecular docking. Date analysis showed that the active composition of HB in the treatment of OLP were quercetin, wogonin, kaempferol, and luteolin. This survey identified 10 potential therapeutic targets, including TNF, CXCL8, IL-6, IL1B, PIK3R1, ESR1, JUN, AKT1, PIK3CA, and CTNNB1. Molecular docking revealed stable interactions between OLP' key targets and HB. These key targets were predominantly involved in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway. HB plays a crucial role in the treatment of OLP, acting on multiple targets and pathways, particularly the PI3K-Akt signaling pathway. It regulated biological processes like the proliferation of epithelial cells and lymphocytes and mediates the expression of transcription factors, cytokines, and chemokines. Therefore, this study provides a theoretical basis for the clinical trial and application of HB in the therapy of OLP.
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Medicamentos Herbarios Chinos , Liquen Plano Oral , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/metabolismo , Flavanonas/farmacología , Flavanonas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Quempferoles/farmacología , Quempferoles/uso terapéutico , Quercetina/farmacología , Quercetina/uso terapéutico , Luteolina/farmacología , Luteolina/uso terapéuticoRESUMEN
Although phytochemicals are plant-derived toxins that are primarily produced as a form of defense against insects or microbes, several lines of study have demonstrated that the phytochemical, quercetin, has several beneficial biological actions for human health, including antioxidant and inflammatory effects without side effects. Quercetin is a flavonoid that is widely found in fruits and vegetables. Since recent studies have demonstrated that quercetin can modulate neuronal excitability in the nervous system, including nociceptive sensory transmission via mechanoreceptors and voltage-gated ion channels, and inhibit the cyclooxygenase-2-cascade, it is possible that quercetin could be a complementary alternative medicine candidate; specifically, a therapeutic agent against nociceptive and pathological pain. The focus of this review is to elucidate the neurophysiological mechanisms underlying the modulatory effects of quercetin on nociceptive neuronal activity under nociceptive and pathological conditions, without inducing side effects. Based on the results of our previous research on trigeminal pain, we have confirmed in vivo that the phytochemical, quercetin, demonstrates (i) a local anesthetic effect on nociceptive pain, (ii) a local anesthetic effect on pain related to acute inflammation, and (iii) an anti-inflammatory effect on chronic pain. In addition, we discuss the contribution of quercetin to the relief of nociceptive and inflammatory pain and its potential clinical application.
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Fitoquímicos , Quercetina , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Animales , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/química , Dolor/tratamiento farmacológico , Dolor Nociceptivo/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/química , Inflamación/tratamiento farmacológico , Nocicepción/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/químicaRESUMEN
This study aimed to investigate the mechanism of quercetin increasing growth performance and decreasing incidence of diarrhea in weaned piglets. Forty-eight Duroc × Landrace × Large White weaned piglets with similar body weight (7.48 ± 0.20 kg, 28 days of age) were randomly divided into four treatments (control, 250 mg/kg quercetin, 500 mg/kg quercetin, and 750 mg/kg quercetin treatments) and fed with basal diet or experimental diet supplemented with quercetin. Performance, diarrhea rate and index, and content of serum anti-inflammatory factors were determined and calculated in weaned piglets; colonic flora and signaling pathways related to anti-inflammation were measured using 16S rDNA sequencing and RNA-seq, respectively. The results showed that compared with control, feed-to-gain ratio and content of serum interferon gamma (IFN-γ) were significantly decreased in the 500 and 750 mg/kg quercetin treatments (P < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index (P < 0.05) and significantly increased the content of serum transforming growth factor (TGF-ß) in weaned piglets (P < 0.05); the content of serum NF-κB was significantly decreased in the 750 mg/kg quercetin treatment (P < 0.05); moreover, quercetin significantly increased diversity of colonic flora (P < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased (P < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased (P < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of Clostridium-sensu-stricto-1, Turicibacter, unclassified_f_Lachnospiraceae, Phascolarctobacterium, and Family_XIII _AD3011_group was significantly increased (P < 0.05); the relative abundance of Subdollgranulum and Blautia was significantly decreased in the 500 and 750 mg/kg treatments (P < 0.05); the relative abundance of Eschericha-Shigella, Terrisporobacter, and Eubacterium-coprostanoligenes was significantly increased (P < 0.05); the relative abundance of Streptocococcus, Sarcina, Staphylococcus, and Ruminococcaceae_UCG-008 was significantly decreased in the three quercetin treatments (P < 0.05); the relative abundance of Ruminococcaceae_UCG_014 was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets (P < 0.05). The results of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differentially expressed genes (DEGs) from the quercetin treatments were significantly enriched in nuclear transcription factor-κB (NF-κB) signal pathway (P < 0.05); mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1R1 (IL-1R1), conserved helix-loop-helix ubiquitous kinase (CHUK), toll-like receptor 4 (TLR4), and IL-1ß from quercetin treatments were significantly decreased in colonic mucosa of weaned piglets (P < 0.05). In summary, quercetin increased feed conversion ratio and decreased diarrhea through regulating NF-κB signaling pathway, controlling the balance between anti-inflammatory and proinflammatory factors, and modulating intestinal flora, thus promoting the absorption of nutrients in weaned piglets. These results provided the theoretical foundation for applying quercetin in preventing weaning piglets' diarrhea and animal husbandry practices.
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Diarrea , Quercetina , Destete , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Porcinos , Diarrea/veterinaria , Diarrea/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/tratamiento farmacológico , IncidenciaRESUMEN
This study aimed to investigate the antioxidant and anti-inflammatory properties of quercetin on the cellular components of the Enteric Nervous System in the ileum of rats with arthritis. Rats were distributed into five groups: control (C), arthritic (AIA), arthritic treated with ibuprofen (AI), arthritic treated with quercetin (AQ) and arthritic treated with both ibuprofen and quercetin (AIQ). The ileum was processed for immunohistochemical techniques for HuC/D, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. Measurements in histological sections, chemiluminescence assays, and total antioxidant capacity were also performed. Rheumatoid arthritis resulted in a decrease in neuronal density, yet neuroplasticity mechanisms were evident through observed changes in varicosities size and neuronal area compared to the control group. Reduced paw edema and neuroprotective effects were predominantly noted in both plexuses, as evidenced by the increased density preservation of HuC/D-IR neurons in the AIQ group. The increase of lipoperoxidation levels and paw edema volume in the AQ group was observed compared to the arthritic, whereas the AIQ group mainly showed similar results to those observed in the control. The enteropathy associated with arthritis proved to be significant in the field of gastroenterology, and the combination of quercetin and ibuprofen demonstrated promising anti-inflammatory and neuroprotective effects.
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Antiinflamatorios , Antioxidantes , Ibuprofeno , Quercetina , Ratas Wistar , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Ratas , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Neuronas/efectos de los fármacos , Neuronas/patología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Sistema Nervioso Entérico/efectos de los fármacos , Sistema Nervioso Entérico/patología , Inmunohistoquímica , Íleon/efectos de los fármacos , Íleon/patologíaRESUMEN
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
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Quercetina , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Animales , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hepatopatías/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/lesiones , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/químicaRESUMEN
Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.
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Cartílago Articular , Condrocitos , Modelos Animales de Enfermedad , Ferroptosis , Factor 2 Relacionado con NF-E2 , Osteoartritis , Quercetina , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Osteoartritis/patología , Ratas , Quercetina/farmacología , Quercetina/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Ferroptosis/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Cartílago Articular/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Ratas Sprague-Dawley , Interleucina-1beta/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismoRESUMEN
Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 .
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Huesos , Posmenopausia , Quercetina , Humanos , Femenino , Posmenopausia/efectos de los fármacos , Persona de Mediana Edad , Anciano , Huesos/efectos de los fármacos , Huesos/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/administración & dosificación , Dasatinib/farmacología , Dasatinib/uso terapéutico , Dasatinib/administración & dosificación , Procolágeno/metabolismo , Procolágeno/sangre , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Senoterapéuticos/farmacología , Senoterapéuticos/uso terapéutico , Fragmentos de Péptidos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Densidad Ósea/efectos de los fármacos , Biomarcadores/metabolismo , Resorción Ósea/tratamiento farmacológico , Péptidos/farmacología , Senescencia Celular/efectos de los fármacosRESUMEN
Quercetin, a bioactive plant flavonoid, is an antioxidant, and as such it exhibits numerous beneficial properties including anti-inflammatory, antiallergic, antibacterial and antiviral activity. It occurs naturally in fruit and vegetables such as apples, blueberries, cranberries, lettuce, and is present in plant waste such as onion peel or grape pomace which constitute good sources of quercetin for technological or pharmaceutical purposes. The presented study focuses on the role of quercetin in prevention and treatment of dermatological diseases analyzing its effect at a molecular level, its signal transduction and metabolism. Presented aspects of quercetin potential for skin treatment include protection against aging and UV radiation, stimulation of wound healing, reduction in melanogenesis, and prevention of skin oxidation. The article discusses quercetin sources (plant waste products included), methods of its medical administration, and perspectives for its further use in dermatology and diet therapy.
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Quercetina , Enfermedades de la Piel , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/prevención & control , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Medicina Preventiva , Animales , Fitoquímicos/uso terapéutico , Fitoquímicos/química , Fitoquímicos/farmacología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Background: Mistletoe is an herb that grows on duku plants (Lancium demosticum) and is known as benalu duku (BD) in Indonesia. It is predicted to have benefits such as anticancer or antiviral properties, and it is also thought to have anti-diabetic pharmacological activity. Quercetin-like compounds (QLCs) are secondary metabolites with antidiabetic activity that are expected to lower blood sugar levels in animals after oral administration.Objective: This study aimed to analyze the ability of QLCs to reduce random blood sugar levels using experimental animals as clinical models.Material and methods: The research method used was exploratory, which used a before-after test model, and observations were made on the random blood sugar levels after treatment. Secondary metabolites were extracted from BD leaves, which were then screened. Diabetes was induced in 30 rats (Rattus norvegicus) by the administration of streptozotocin at 0.045 mg/g body weight daily for 2 days. The antidiabetic effects of the secondary metabolite at doses of 0.5 mg/kg body weight (twice a day) when administered orally for up to 5 days were tested in diabetic rats. The random sugar levels (mg/dL) were measured using a One Touch Ultra Plus medical device for observation of randomized blood sugar levels. Results and novelty: The results revealed that the secondary metabolite, as an analyte from the BD leaf extract, can significantly reduce random blood sugar levels.Conclusion: The secondary metabolite extracted from BD, could be used to treat diabetes in rats.
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Glucemia , Diabetes Mellitus Experimental , Hipoglucemiantes , Extractos Vegetales , Quercetina , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/sangre , Ratas , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/uso terapéutico , Glucemia/análisis , Glucemia/efectos de los fármacos , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Muérdago/química , Administración Oral , Hojas de la Planta/químicaRESUMEN
Introduction: With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need to discover effective therapeutic targets for this complex condition. Coding and non-coding RNAs, with traditional biochemical parameters, have shown promise as viable targets for therapy. Machine learning (ML) techniques have emerged as powerful tools for predicting drug responses. Method: In this study, we developed an ML-based model to identify the most influential features for drug response in the treatment of type 2 diabetes using three medicinal plant-based drugs (Rosavin, Caffeic acid, and Isorhamnetin), and a probiotics drug (Z-biotic), at different doses. A hundred rats were randomly assigned to ten groups, including a normal group, a streptozotocin-induced diabetic group, and eight treated groups. Serum samples were collected for biochemical analysis, while liver tissues (L) and adipose tissues (A) underwent histopathological examination and molecular biomarker extraction using quantitative PCR. Utilizing five machine learning algorithms, we integrated 32 molecular features and 12 biochemical features to select the most predictive targets for each model and the combined model. Results and discussion: Our results indicated that high doses of the selected drugs effectively mitigated liver inflammation, reduced insulin resistance, and improved lipid profiles and renal function biomarkers. The machine learning model identified 13 molecular features, 10 biochemical features, and 20 combined features with an accuracy of 80% and AUC (0.894, 0.93, and 0.896), respectively. This study presents an ML model that accurately identifies effective therapeutic targets implicated in the molecular pathways associated with T2DM pathogenesis.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Aprendizaje Automático , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Ratas Sprague-Dawley , Biomarcadores , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Resistencia a la Insulina , Quercetina/farmacología , Quercetina/uso terapéutico , Ácidos CafeicosRESUMEN
The escalating global incidence of cancer, which results in millions of fatalities annually, underscores the pressing need for effective pharmacological interventions across diverse cancer types. Long noncoding RNAs (lncRNAs), a class of RNA molecules that lack protein-coding capacity but profoundly impact gene expression regulation, have emerged as pivotal players in key cellular processes, including proliferation, apoptosis, metastasis, cellular metabolism, and drug resistance. Among natural compounds, quercetin, a phenolic compound abundantly present in fruits and vegetables has garnered attention due to its significant anticancer properties. Quercetin demonstrates the ability to inhibit cancer cell growth and induce apoptosis-a process often impaired in malignant cells. In this comprehensive review, we delve into the therapeutic potential of quercetin in cancer treatment, with a specific focus on its intricate interactions with lncRNAs. We explore how quercetin modulates lncRNA expression and function to exert its anticancer effects. Notably, quercetin suppresses oncogenic lncRNAs that drive cancer development and progression while enhancing tumor-suppressive lncRNAs that impede cancer growth and dissemination. Additionally, we discuss quercetin's role as a chemopreventive agent, which plays a crucial role in mitigating cancer risk. We address research challenges and future directions, emphasizing the necessity for in-depth mechanistic studies and strategies to enhance quercetin's bioavailability and target specificity. By synthesizing existing knowledge, this review underscores quercetin's promising potential as a novel therapeutic strategy in the ongoing battle against cancer, offering fresh insights and avenues for further investigation in this critical field.
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Neoplasias , Quercetina , ARN Largo no Codificante , Quercetina/farmacología , Quercetina/uso terapéutico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacosRESUMEN
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
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Apoptosis , Movimiento Celular , Melanoma , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Quercetina , Transducción de Señal , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones DesnudosRESUMEN
In intracerebral hemorrhage (ICH), the mechanical brain injury is a considerable and indispensable factor determining the neurological functions and poor outcomes. Previous studies indicate the mechanically gated ion channel-Piezo1 can transduce mechanical effects following ICH. Isoquercitrin (ISQ) is a well-studied ion channel inhibitor. Furthermore, whether the following Piezo1-mediated neurological impairment can be ameliorated by ISQ remains unclear. Herein, we constructed the hydrostatic pressure model and ICH rat model. Firstly, we found that Piezo1 agonists Yoda1 and Jedi1 facilitated extracellular calcium influx dramatically, but ISQ could depress intracellular Ca2+ overload under hydrostatic pressure in primary neurons. Then we detected the expression profile of Piezo1, NLRP3 and NF-κB p-p65 after ICH, and found that the expression of Piezo1 was much earlier than NLRP3 and NF-κB p-p65. Furthermore, by western blot and immunofluorescence, ISQ decreased the expression of Piezo1 and NLRP3 dramatically like GsMTx4, but Nigericin as a NLRP3 agonist failed to affect Piezo1. Besides, both ISQ and interfering Piezo1 suppressed the upregulated caspase-1, NF-κB p-p65, p-IκBα, Tunel-positive cells and inflammatory factors (IL-1ß, IL-6 and TNF-α) in ICH. At last, the hydrostatic pressure or hematoma induced disturbed neural viability, disordered neural cytomorphology, and increased neurobehavioral and cognitive deficits, but they were improved by ISQ and GsMTx4 strongly. Therefore, ISQ could alleviate neurological injuries induced by Piezo1 via NLRP3 pathway. These observations indicated that Piezos might be the new therapeutic targets, and blocking Piezos/NLRP3 pathway by ISQ could be an auspicious strategy for the treatment of ICH.
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Hemorragia Cerebral , Canales Iónicos , Proteína con Dominio Pirina 3 de la Familia NLR , Quercetina , Ratas Sprague-Dawley , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ratas , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/patología , Masculino , Canales Iónicos/metabolismo , Canales Iónicos/antagonistas & inhibidores , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Neuronas/efectos de los fármacos , Neuronas/metabolismoRESUMEN
Background: Cytokine release syndrome (CRS) is the leading cause of mortality in advanced stages of coronavirus patients. This study examined the prophylactic effects of fraxin, quercetin, and a combination of fraxin+quercetin (FQ) on lipopolysaccharide-induced mice. Methods: Sixty mice were divided into six groups (n=10) as follows: control, LPS only, fraxin (120 mg/Kg), quercetin (100 mg/Kg), dexamethasone (5 mg/Kg), and FQ. All treatments were administered intraperitoneally (IP) one hour before induction by LPS (5 mg/Kg) IP injection. Twenty-four hours later, the mice were euthanized. Interleukin one beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA), and lung and kidney tissues were examined for histopathological alterations. This study was conducted at Al-Nahrain University, Baghdad, Iraq, in 2022. Results: FQ reduced IL-1ß (P<0.001). All treatments significantly suppressed IL-6, fraxin, quercetin, dexamethasone, and FQ, all with P<0.001. The TNF-α level was reduced more with dexamethasone (P<0.001) and quercetin (P<0.001). Histopathological scores were significantly reduced mainly by quercetin and FQ in the lungs with scores of 12.30±0.20 (P=0.093), and 15.70±0.20 (P=0.531), respectively. The scores were 13±0.26 (P=0.074) and 15±0.26 (P=0.222) for quercetin and FQ in the kidneys, respectively. Conclusion: All used treatments reduced proinflammatory cytokine levels and protected against LPS-induced tissue damage.
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Síndrome de Liberación de Citoquinas , Lipopolisacáridos , Quercetina , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Ratones , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Lipopolisacáridos/farmacología , Tratamiento Farmacológico de COVID-19 , Masculino , COVID-19 , Dexametasona/farmacología , Dexametasona/uso terapéutico , Interleucina-6/sangre , Interleucina-6/análisis , Citocinas/efectos de los fármacos , Interleucina-1beta , Factor de Necrosis Tumoral alfa , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , CumarinasRESUMEN
Yinchenhao Decoction (YCHD) is a classic prescription in traditional Chinese medicine (TCM). It appears to play an important role in anti-inflammation and autoimmunity protection. As one of the key active ingredients in YCHD, quercetin is a novel anti-inflammatory metabolite that exerts protective effects in many autoimmune diseases. However, its role in autoimmune hepatitis (AIH)-related hepatic injury has not been studied. The aim of this study was to reveal the hepatocyte protective mechanism of quercetin. In this study, we used Concanavalin A (Con A) to establish an in vitro hepatocyte injury-associated AIH model. Brl3a hepatocyte injury was induced by the supernatant of J774A.1 cells treated with Con A. We found that quercetin mitigated Con A-induced via macrophage-mediated Brl3a hepatocyte injury. Quercetin administration reduced the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in the supernatant of Con A-treated Brl3a cells and attenuated the infiltration of J774A.1 macrophages induced by Con A. Moreover, quercetin effectively inhibited the expression of proinflammatory cytokines including interleukin-1ß (IL-1ß) by Con A. Furthermore, quercetin decreased hepatocyte apoptosis and ferroptosis levels in the macrophage-induced hepatocyte injury model. In conclusion, our study indicates that quercetin alleviates macrophage-induced hepatocyte damage by reducing the inflammatory response, apoptosis and ferroptosis. Our work suggests that quercetin might be a potential therapeutic strategy for AIH.