RESUMEN
Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca2+, and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca2+, higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes.
Asunto(s)
Criopreservación , Mitocondrias , Oocitos , Rutina , Vitrificación , Animales , Rutina/farmacología , Oocitos/efectos de los fármacos , Oocitos/fisiología , Ovinos/fisiología , Mitocondrias/efectos de los fármacos , Vitrificación/efectos de los fármacos , Criopreservación/veterinaria , Especies Reactivas de Oxígeno/metabolismo , Femenino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Antioxidantes/farmacología , Desarrollo Embrionario/efectos de los fármacosRESUMEN
BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Pruebas de Sensibilidad Microbiana , Nanopartículas , Rutina , Staphylococcus aureus , Xantófilas , Staphylococcus aureus/efectos de los fármacos , Quitosano/farmacología , Quitosano/química , Rutina/farmacología , Rutina/química , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Xantófilas/farmacología , Xantófilas/química , Hemólisis/efectos de los fármacos , Factores de Virulencia , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Peróxido de Hidrógeno/farmacologíaRESUMEN
The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20â min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.
Asunto(s)
Analgésicos , Arginina , GMP Cíclico , Canales KATP , NG-Nitroarginina Metil Éster , Óxido Nítrico , Receptores Opioides , Rutina , Transducción de Señal , Animales , Masculino , Ratones , Arginina/farmacología , Óxido Nítrico/metabolismo , Rutina/farmacología , Analgésicos/farmacología , Transducción de Señal/efectos de los fármacos , Receptores Opioides/metabolismo , Receptores Opioides/efectos de los fármacos , Canales KATP/metabolismo , GMP Cíclico/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Gliburida/farmacología , Citrato de Sildenafil/farmacología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Naloxona/farmacología , Sulfonas/farmacología , Piperazinas/farmacología , Purinas/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , Dolor/tratamiento farmacológico , Dolor/metabolismo , Antagonistas de Narcóticos/farmacología , Relación Dosis-Respuesta a Droga , Donantes de Óxido Nítrico/farmacologíaRESUMEN
Tyrosinase is a binuclear copper-containing enzyme that catalyzes the conversation of monophenols to diphenols via o-hydroxylation and then the oxidation of o-diphenols to o-quinones which is profoundly linked to eukaryotic melanin synthesis and fruits browning. The hyperpigmentation due to unusual tyrosinase activity has gained growing health concern. Plants and their metabolites are considered promising and effective sources for potent antityrosinase enzymes. Hence, searching for potent, specific tyrosinase inhibitor from different plant extracts is an alternative approach in regulating overproduction of tyrosinase. Among the tested extracts, the hydro-alcoholic extract of Moringa oleifera L. leaves displayed the potent anti-tyrosinase activity (IC50 = 98.93 µg/ml) in a dose-dependent manner using L-DOPA as substrate; however, the kojic acid showed IC50 of 88.92 µg/ml. The tyrosinase-diphenolase (TYR-Di) kinetic analysis revealed mixed inhibition type for the Ocimum basilicum L. and Artemisia annua L. extracts, while the Coriandrum sativum L. extract displayed a non-competitive type of inhibition. Interestingly, the extract of Moringa oleifera L. leaves exhibited a competitive inhibition, low inhibition constant of free enzyme ( K ii app ) value and no Pan-Assay Interfering Substances, hinting the presence of strong potent inhibitors. The major putative antityrosinase compound in the extract was resolved, and chemically identified as rutin based on various spectroscopic analyses using UV-Vis, FTIR, mass spectrometry, and 1H NMR. The in silico computational molecular docking has been performed using rutin and A. bisporus tyrosinase (PDB code: 2Y9X). The binding energy of the predicted interaction between tropolone native ligand, kojic acid, and rutin against 2Y9X was respectively - 5.28, - 4.69, and - 7.75 kcal/mol. The docking simulation results revealed the reliable binding of rutin to the amino acid residues (ASN260, HIS259, SER282) in the tyrosinase catalytic site. Based on the developed results, rutin extracted from M. oleifera L. leaves has the capability to be powerful anti-pigment agent with a potential application in cosmeceutical area. In vivo studies are required to unravel the safety and efficiency of rutin as antityrosinase compound.
Asunto(s)
Agaricus , Inhibidores Enzimáticos , Simulación de Dinámica Molecular , Monofenol Monooxigenasa , Moringa oleifera , Extractos Vegetales , Rutina , Moringa oleifera/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/química , Agaricus/enzimología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Rutina/química , Rutina/farmacología , Rutina/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Simulación del Acoplamiento Molecular , Hojas de la Planta/química , CinéticaRESUMEN
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.
Asunto(s)
Antioxidantes , Flavonoides , Extractos Vegetales , Hojas de la Planta , Hojas de la Planta/química , Flavonoides/farmacología , Flavonoides/química , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Egipto , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Fenoles/farmacología , Fenoles/química , Rutina/farmacología , Rutina/química , Sophora japonicaRESUMEN
Digital light processing (DLP) bioprinting, known for its high resolution and speed, enables the precise spatial arrangement of biomaterials and has become integral to advancing tissue engineering and regenerative medicine. Nevertheless, inherent light scattering presents significant challenges to the fidelity of the manufactured structures. Herein, we introduce a photoinhibition strategy based on Rutin nanoparticles (Rnps), attenuating the scattering effect through concurrent photoabsorption and free radical reaction. Compared to the widely utilized biocompatible photoabsorber tartrazine (Tar), Rnps-infused bioink enhanced printing speed (1.9×), interlayer homogeneity (58% less overexposure), resolution (38.3% improvement), and print tolerance (3× high-precision range) to minimize trial-and-error. The biocompatible and antioxidative Rnps significantly improved cytocompatibility and exhibited resistance to oxidative stress-induced damage in printed constructs, as demonstrated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). The related properties of Rnps facilitate the facile fabrication of multimaterial, heterogeneous, and cell-laden biomimetic constructs with intricate structures. The developed photoinhibitor, with its profound adaptability, promises wide biomedical applications tailored to specific biological requirements.
Asunto(s)
Bioimpresión , Luz , Nanopartículas , Rutina , Humanos , Rutina/química , Rutina/farmacología , Nanopartículas/química , Ingeniería de Tejidos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.
Asunto(s)
Neoplasias Colorrectales , Biología Computacional , Especies Reactivas de Oxígeno , Rutina , Rutina/farmacología , Rutina/química , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory skin disease that can cause systemic inflammation in various organs. Rutin has been suggested to fight psoriasis, but the signaling pathways by which it works need to be explored. MATERIALS AND METHODS: HaCaT cells co-stimulated with interleukin (IL)-17, IL-22, tumor necrosis factor-alpha (TNF-α), IL-1α, and oncostatin M (M5) were used as an in vitro cell model of psoriasis. The proliferation and viability of HaCaT cells were determined by 5-ethynyl-2'-deoxyuridine and cell counting assays. Relative mRNA levels of IL-6, TNF-α, chemokines (CXCL1 and CXCL2), and anti-microbial peptides (S100A7 and S100A8) were detected by reverse transcriptase-quantitative PCR. Release of IL-6 and TNF-α from HaCaT cells was measured by enzyme-linked immunosorbent assay. Keratin1, Keratin5, p-JAK2, and p-STAT3 protein levels were estimated with western blotting. Molecular docking predicted binding sites for Rutin and STAT3. RESULTS: Rutin treatment undercut M5-urged viability increase and proliferation boost in HaCaT cells. Moreover, M5 stimulation mediated upregulation of IL-6, TNF-α, CXCL1, CXCL2, S100A7, and S100A8 was partially reversed after Rutin treatment. In addition, M5 stimulation induced downregulation of Keratin1 and Keratin5 proteins as well as upregulation of p-JAK2 and p-STAT3 proteins were attenuated in response to Rutin treatment, manifesting that Rutin treatment inhibited M5-promoted aberrant differentiation and impaired M5-mediated activation of the JAK2/STAT3 signaling in HaCaT cells. Molecular docking discovered that residues GLN326 and ASP334 in STAT3 might bind to Rutin. CONCLUSION: Rutin treatment blocked the JAK2/STAT3 signaling, thus attenuating psoriasis-related inflammation and anomalous differentiation in keratinocytes.
Asunto(s)
Janus Quinasa 2 , Queratinocitos , Psoriasis , Rutina , Factor de Transcripción STAT3 , Transducción de Señal , Humanos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células HaCaT , Inflamación/metabolismo , Janus Quinasa 2/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Simulación del Acoplamiento Molecular , Psoriasis/metabolismo , Psoriasis/tratamiento farmacológico , Rutina/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismoRESUMEN
BACKGROUND: The vulnerability of buffalo sperm to cryoinjury necessitates the improvement of sperm cryo-resistance as a critical strategy for the widespread use of assisted reproductive technologies in buffalo. OBJECTIVES: The main aim of the present study was to evaluate the effects of different concentrations of rutin and chlorogenic acid (CGA) on buffalo semen quality, antioxidant activity and fertility during cryopreservation. METHODS: The semen was collected and pooled from the 3 buffaloes using an artificial vagina (18 ejaculations). The pooled sperm were divided into nine different groups: control (Tris-based extender); 0.4, 0.6, 0.8 and 1 mM rutin (rutin + Tris-based extender); and 50, 100, 150 and 200 µM CGG (CGA + Tris-based extender). Sperm kinematics, viability, hypo-osmotic swelling test, mitochondrial activity, antioxidant activities and malondialdehyde (MDA) concentration of frozen and thawed buffalo sperm were evaluated. In addition, 48 buffalo were finally inseminated, and pregnancy was rectally determined 1 month after insemination. RESULTS: Compared to the control group, adding R-0.4, R-0.6, CGA-100 and CGA-150 can improve total and progressive motility, motility characteristics, viability, PMF and DNA damage in buffalo sperm. In addition, the results showed that R-0.4, R-0.6, CGA-50, CGA-100 and CGA-150 increased total antioxidant capacity, catalase, glutathione peroxidase and glutathione activities and decreased MDA levels compared to the control group. Furthermore, it has been shown that adding 150 µM CGA and 0.6 mM rutin to an extender can increase in vivo fertility compared to the control group. CONCLUSIONS: In conclusion, adding rutin and CGA to the extender improves membrane stability and in vivo fertility of buffalo sperm by reducing oxidative stress.
Asunto(s)
Antioxidantes , Búfalos , Ácido Clorogénico , Criopreservación , Fertilidad , Estrés Oxidativo , Rutina , Análisis de Semen , Preservación de Semen , Animales , Búfalos/fisiología , Masculino , Rutina/farmacología , Estrés Oxidativo/efectos de los fármacos , Ácido Clorogénico/farmacología , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Antioxidantes/farmacología , Análisis de Semen/veterinaria , Fertilidad/efectos de los fármacos , Criopreservación/veterinaria , Semen/efectos de los fármacos , Semen/fisiología , Femenino , Espermatozoides/efectos de los fármacos , Espermatozoides/fisiología , Relación Dosis-Respuesta a DrogaRESUMEN
Effective wound care remains a significant challenge due to the need for infection prevention, inflammation reduction, and minimal tissue damage during dressing changes. To tackle these issues, we have developed a multifunctional hydrogel (CHI/CPBA/RU), composed of chitosan (CHI) modified with 4-carboxyphenylboronic acid (CPBA) and the natural flavonoid, rutin (RU). This design endows the hydrogel with body temperature-responsive adhesion and low temperature-triggered detachment, thus enabling painless removal during dressing changes. The CHI/CPBA/RU hydrogels exhibit excellent biocompatibility, maintaining over 97 % viability of L929 cells. They also demonstrate potent intracellular free radical scavenging activity, with scavenging ratios ranging from 53 % to 70 %. Additionally, these hydrogels show anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, and iNOS) and increasing anti-inflammatory markers (Arg1 and CD206) in RAW 264.7 macrophages. Notably, they possess robust antimicrobial properties, inhibiting over 99.9 % of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth. In vivo testing on a murine full-thickness skin defect model shows that the hydrogel significantly accelerates wound healing by reducing inflammation, increasing collagen deposition, and promoting angiogenesis, achieving 98 % healing by day 10 compared to 78 % in the control group. These attributes make the polysaccharide-based hydrogel a promising material for advanced wound care.
Asunto(s)
Antibacterianos , Antiinflamatorios , Quitosano , Hidrogeles , Rutina , Piel , Staphylococcus aureus , Cicatrización de Heridas , Animales , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Células RAW 264.7 , Antibacterianos/farmacología , Antibacterianos/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Piel/efectos de los fármacos , Rutina/farmacología , Rutina/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.
Asunto(s)
Acrilamida , Daño del ADN , Inflamación , Estrés Oxidativo , Rutina , Animales , Rutina/farmacología , Femenino , Estrés Oxidativo/efectos de los fármacos , Acrilamida/toxicidad , Daño del ADN/efectos de los fármacos , Ratas , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Ratas Wistar , Simulación por Computador , Antioxidantes/farmacología , Antioxidantes/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.
Asunto(s)
Antiinflamatorios , Carragenina , Edema , Simulación del Acoplamiento Molecular , Corteza de la Planta , Extractos Vegetales , Hojas de la Planta , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Hojas de la Planta/química , Corteza de la Planta/química , Masculino , Relación Estructura-Actividad , Peroxidasa/metabolismo , Fabaceae/química , Antivenenos/farmacología , Antivenenos/química , Ratas Wistar , Venenos de Crotálidos/toxicidad , Ratones , Bothrops , Citocinas/metabolismo , Zimosan , Biomarcadores/metabolismo , Rutina/farmacologíaRESUMEN
Lead (Pb) is harmful to almost all organs, particularly the developmental neural system, and previous studies revealed oxidative stress played an important role in Pb neurotoxicity. Rutin, a type of flavonoid glycoside found in various plants and fruits, is widely used as a dietary supplement due to its antioxidant and anti-inflammatory properties, but whether rutin could protect against Pb neurotoxicity is unclear. In this study, we found rutin treatment significantly alleviated Pb-induced cell death, oxidative stress, and inflammation, resulting in cell survival. Moreover, rutin treatment promoted nuclear factor erythroid 2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and subsequently activated antioxidant and detoxifying enzymes expression including HO-1. Knocking down Nrf2 by siRNA transfection abolished this protection of rutin against Pb. Overall, rutin could alleviate Pb-induced oxidative stress, inflammation, and cell death by activating the Nrf2/antioxidant response elements (ARE) system.
Asunto(s)
Elementos de Respuesta Antioxidante , Muerte Celular , Plomo , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Rutina , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Rutina/farmacología , Humanos , Muerte Celular/efectos de los fármacos , Plomo/toxicidad , Línea Celular Tumoral , Elementos de Respuesta Antioxidante/efectos de los fármacos , Inflamación/metabolismo , Inflamación/inducido químicamente , Fármacos Neuroprotectores/farmacología , Supervivencia Celular/efectos de los fármacos , Antioxidantes/farmacologíaRESUMEN
Inhibition of pancreatic lipase (PL) is a strategy to prevent obesity. The inhibitory effects of Flos Sophorae Immaturus (FSI) extract and its main flavonoid components, rutin and quercetin, on PL were investigated. The contents of rutin and quercetin in FSI extract were 44.10 ± 1.33 % and 6.07 ± 1.62 %, respectively. The IC50 values of FSI extract, rutin and quercetin on PL were 322, 258 and 71 µg/mL, respectively. Rutin and quercetin inhibited PL in a reversible and noncompetitive manner. The combination of rutin and quercetin exhibited synergistic inhibitory effects at low concentration. The binding of rutin/quercetin with PL caused the fluorescence quenching of protein. Fluorescence titration showed the binding affinity of quercetin with PL protein was stronger than that of rutin. Circular dichroism analysis showed the binding changed the secondary structure of PL with an increase in random coil and a decrease in α-Helix and ß-Sheet. Molecular docking revealed that rutin and quercetin could interact with the amino acid residues around the catalytic site through multiple secondary interactions. In vivo studies showed that FSI extract can reduce fat absorption and promote fecal fat excretion through inhibition of PL activity, and the effects were mainly due to rutin and quercetin.
Asunto(s)
Flavonoides , Lipasa , Simulación del Acoplamiento Molecular , Páncreas , Extractos Vegetales , Quercetina , Rutina , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Lipasa/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Quercetina/farmacología , Quercetina/química , Páncreas/enzimología , Páncreas/efectos de los fármacos , Flavonoides/farmacología , Flavonoides/química , Rutina/farmacología , Rutina/química , Animales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Masculino , Sophora/químicaRESUMEN
The blood-brain barrier (BBB) prevents the use of many drugs for the treatment of neurological disorders. Recently, nitrogen-doped carbon dots (NCDs) have emerged as promising nanocarriers to cross BBB. The primary focus of our study was to evaluate the effectiveness of NCDs for the symptomatic treatment of Alzheimer's disease (AD). In this study, we developed and characterized NCDs bound to rutin, a flavonoid with known benefits for AD. Despite its benefits, the transportation of rutin via NCDs for AD therapy has not been explored previously. We characterized the particles using FTIR and UV-visible spectroscopy followed by atomic force microscopy. Once the design was optimized and validated, we performed in vivo testing via a hemolytic assay to optimize the dosage. Preliminary in vitro testing was performed in AlCl3-induced rat models of AD whereby a single dose of 10 mg/kg NCDs-rutin was administered intraperitoneally. Interestingly, this single dose of 10 mg/kg NCDs-rutin produced the same behavioral effects as 50 mg/kg rutin administered intraperitoneally for 1 month. Similarly, histological and biomarker profiles (SOD2 and TLR4) also presented significant protective effects of NCDs-rutin against neuronal loss, inflammation, and oxidative stress. Hence, NCDs-rutin are a promising approach for the treatment of neurological diseases.
Asunto(s)
Enfermedad de Alzheimer , Carbono , Glucosa , Nitrógeno , Rutina , Rutina/farmacología , Rutina/química , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Carbono/química , Carbono/farmacología , Nitrógeno/química , Ratas , Glucosa/metabolismo , Masculino , Puntos Cuánticos/química , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , HumanosRESUMEN
This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.
Asunto(s)
Antioxidantes , Neoplasias de la Mama , Daño del ADN , Flavanonas , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Rutina , Humanos , Flavanonas/farmacología , Rutina/farmacología , Daño del ADN/efectos de los fármacos , Antioxidantes/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Estrés Oxidativo/efectos de los fármacos , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Supervivencia Celular/efectos de los fármacosRESUMEN
Zearalenone (ZEN) poses a potential threat on human and animal health partly through the nuclear factor (NF)-κB signaling pathway. In silico study suggested that rutin effective against TLR4 and NF-κB. A wetting test was designed to evaluate the effect and underlying mechanism of rutin in alleviating ZEN-induced inflammation in animals. Twenty-four female mice were randomly divided into 4 groups: control (basal diet), ZEN group (basal diet + ZEN), rutin group (basic diet + rutin), Z + R group (basal diet + rutin + ZEN). Results showed that rutin effectively alleviated ZEN-induced inflammation and damage of liver and jejunum in mice. Rutin addition reduced the content of lipopolysaccharide (LPS) in serum and liver mainly by improving the intestinal barrier function resulted from the production increase of short-chain fatty acids (SCFA). In sum, this study showed that rutin alleviated ZEN-induced liver inflammation and injury by modulating the gut microbiota, increasing the production of SCFA and improving intestinal barrier function, leading to the decrease of LPS in liver and the inhibition of MyD88 independent NF-κB signaling pathway in mice. Specifically, these findings may provide useful insights into the screening of functional natural compounds and its action mechanism to alleviate ZEN induced liver inflammation.
Asunto(s)
Lipopolisacáridos , FN-kappa B , Rutina , Transducción de Señal , Zearalenona , Animales , Zearalenona/toxicidad , Rutina/farmacología , Lipopolisacáridos/toxicidad , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.
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Lesión Pulmonar Aguda , Cerio , Manitol , Nanopartículas , Polímeros , Quercetina , Lesión Pulmonar Aguda/tratamiento farmacológico , Quercetina/farmacología , Quercetina/química , Animales , Manitol/química , Manitol/uso terapéutico , Nanopartículas/química , Ratones , Polímeros/química , Cerio/química , Cerio/farmacología , Cerio/uso terapéutico , Rutina/química , Rutina/farmacología , Rutina/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/química , Humanos , Sinergismo Farmacológico , Modelos Animales de Enfermedad , LipopolisacáridosRESUMEN
Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the ligand-binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through an eco-pharmaco-economic analysis (EPEA). The results revealed that the binding affinities of chemical disinfectants to viral proteins varied significantly (p < 0.005). Rutin demonstrated promising broad-spectrum antiviral efficacy with an LBE of -8.49 ± 0.92 kcal/mol across all tested proteins. Additionally, rutin showed a superior eco-pharmaco-economic profile compared to the other chemicals, effectively balancing high antiviral effectiveness, moderate environmental impact, and affordability. These findings highlight rutin as a key phytochemical for use in remediating viral contaminants.
Asunto(s)
Antivirales , Desinfectantes , Rutina , Desinfectantes/farmacología , Desinfectantes/química , Antivirales/farmacología , Antivirales/química , Rutina/química , Rutina/farmacología , Humanos , Simulación por Computador , Virus/efectos de los fármacos , Proteínas Virales/química , Proteínas Virales/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/química , Unión ProteicaRESUMEN
Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M-1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel ß-sheet, and ß-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.