RESUMO

BACKGROUND: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. METHODS: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. RESULTS: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. CONCLUSION: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.

Assuntos

Autofagia , Diabetes Mellitus Experimental , Neuropatias Diabéticas , Estresse do Retículo Endoplasmático , Flavonoides , Lipossomos , Animais , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Polietilenoglicóis/farmacologia , Aloxano , Ratos Wistar , Ratos Sprague-Dawley

RESUMO

The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses. Blood was collected for serological analysis. Chrysin did not interfere with the blood pressure. Morphologically, the epithelial height increased in TW and decreased in TSHR. Stereology showed an increase in the epithelial and stromal relative frequency, and a decrease in the lumen of TW, whereas the epithelium in TSHR was reduced. Normal alveoli decreased, and hyperplastic alveoli had an increment in TW, whereas in TSHR normal alveoli increased and intense hyperplasia decreased. The secretion area was reduced in TW. Immunohistochemical analysis showed a smaller number of PCNA-positive cells in TW. Finally, the biochemical analysis showed a reduction in malondialdehyde, carbonylated proteins, superoxide dismutase, and catalase in TW and TSHR. We concluded that the chrysin effect is dependent on the context in which this flavonoid is employed. In normal conditions, the anabolic potential of the chrysin was favored, disrupting the morphology of the prostate. However, when used in animals predisposed to develop hyperplasia, this flavonoid attenuates the hyperplastic status, improving the morphology of the gland.

Assuntos

Flavonoides , Próstata , Hiperplasia Prostática , Ratos Endogâmicos SHR , Ratos Wistar , Animais , Masculino , Flavonoides/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Ratos , Próstata/efeitos dos fármacos , Próstata/patologia , Próstata/metabolismo , Superóxido Dismutase/metabolismo , Pressão Sanguínea/efeitos dos fármacos

RESUMO

BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated. METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance. RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine. CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.

Assuntos

Fluoxetina , Receptores de GABA-A , Ratos , Masculino , Animais , Fluoxetina/farmacologia , Pregnanolona , Ratos Wistar , Receptores de GABA , Picrotoxina , Estudos Longitudinais , Antidepressivos/farmacologia , Flavonoides/farmacologia , Ácido gama-Aminobutírico

RESUMO

OBJECTIVES: To evaluate whether the glycosylation of chrysin (CHR) enhances its protective effects against aluminum-induced neurotoxicity. METHODS: To compare the antioxidant, anticholinesterase, and behavioral effects of CHR with its glycosylated form (CHR bonded to ß-d-glucose tetraacetate, denoted as LQFM280), we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (aluminum-induced neurotoxicity in Swiss mice) models. KEY FINDINGS: LQFM280 demonstrated higher antioxidant activity than CHR in both models. Specifically, LQFM280 exhibited the ability to exert antioxidant effects in the cytoplasm of SH-SY5Y cells, indicating its competence in traversing neuronal membranes. Remarkably, LQFM280 proved more effective than CHR in recovering memory loss and counteracting neuronal death in the aluminum chloride mice model, suggesting its increased bioavailability at the brain level. CONCLUSIONS: The glycosylation of CHR with ß-d-glucose tetraacetate amplifies its neuroprotective effects, positioning LQFM280 as a promising lead compound for safeguarding against neurodegenerative processes involving oxidative stress.

Assuntos

Flavonoides , Neuroblastoma , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Camundongos , Animais , Humanos , Alumínio/toxicidade , Glucose/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Antioxidantes/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Linhagem Celular Tumoral

RESUMO

Chrysin is a natural flavonoid that despite having numerous biological properties, its therapeutic value is limited due to its very low solubility in aqueous media. In this work, chrysin was conjugated with methoxypolyethylene glycols (mPEGs) of different molecular weights (350, 500, 750, and 2000 g/mol), affording PEGylated chrysins with high yields and excellent purities. In all cases, an increase in the water solubility of the conjugates was observed, which was highest when 500 g/mol of mPEG was used in the PEGylation reaction. Furthermore, in aqueous solution, PEGylated chrysins formed aggregates of ellipsoid shape. Electrochemical studies showed that the redox properties were conserved after PEGylation. While in vitro antibacterial and antifungal studies probed that the intrinsic activity was conserved, in vitro antitumor activities against HepG2 (liver carcinoma cells) and PC3 (prostate cancer cell) showed that PEGylated chrysins retained the cytotoxic activity and the ability of induction of apoptosis for the evaluated human cancer cells.

Assuntos

Polietilenoglicóis , Neoplasias da Próstata , Masculino , Humanos , Solubilidade , Polietilenoglicóis/química , Flavonoides/farmacologia , Água

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 20% of cases. Due to the lack of a molecular target, limited options are available for TNBC treatment. Radiation therapy (RT) is a treatment modality for the management of TNBC following surgery; however, it has a detrimental effect on surrounding healthy tissues/cells at a higher rate. METHODS: We examined the effect of RT in combination with chrysin as a possible radiosensitizing agent in an MDA-MB-231 cell line as a model of a TNBC. The growth inhibitory effects of chrysin were examined using an MTT assay. Flow cytometry was performed to evaluate apoptosis and expression of hypoxia-induced factor-1α (HIF-1α). The protein expression of p-STAT3/STAT3 and Cyclin D1 was examined using western blotting. Real-time PCR determined apoptotic-related genes (Bax, BCL2, p53). RESULTS: Treatment of MDA-MB-231 cells with chrysin in combination with RT caused synergistic antitumor effects, with an optimum combination index (CI) of 0.495. Our results indicated that chrysin synergistically potentiated RT-induced apoptosis in MDA-MB-231 compared with monotherapies (chrysin and/or RT alone). Expression of HIF-1α was decreased in the cells exposed to combinational therapy. The apoptotic effect of combinational therapy was correlated with increased Bax (pro-apoptotic gene) and p53 levels along with reduced expression of Bcl-2 (anti-apoptotic gene). Increased apoptosis was associated with reduced expression of Cyclin D1, p-STAT3. CONCLUSION: These findings highlight the potential effect of chrysin as a radiosensitizer, indicating the synergistic anti-cancer effect of chrysin and RT in TNBC. Further investigation is warranted in this regard.

Assuntos

Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/genética , Ciclina D1/metabolismo , Linhagem Celular Tumoral , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2/metabolismo , Proliferação de Células , Apoptose

RESUMO

Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as Passiflora coerulea, Passiflora incarnata, and Matricaria chamomilla. This natural molecule exerts diverse pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects. Additionally, in brain structures, such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum, involved in the physiopathology of anxiety and depression disorders, several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors, such as brain-derived neurotrophic factor and the nerve growth factor, and some signaling pathways are affected. The results showed that the anxiolytic and antidepressant-like effects of chrysin occurs through its interaction with specific neurotransmitter systems, principally the GABAergic and the serotonergic, and activation of other neurotrophic factors. However, it is not possible to discard the antioxidant and anti-inflammatory activities of chrysin while producing its anxiolytic- and antidepressant-like effects. Although these results have been obtained principally from pre-clinical research, they consistently demonstrate the potential therapeutic use of flavonoid chrysin as an anxiolytic and antidepressant agent. Therefore, this flavonoid could be considered as a promising novel therapy for anxiety and depression disorders.

Assuntos

Ansiolíticos , Passiflora , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico

RESUMO

We have previously synthesized and characterized the chrysin coordination complex with the oxidovanadium(IV) cation (VIVO(chrys)2) and characterized in ethanolic solution and in solid state. Because suitable single crystals for X-ray diffraction determinations could not be obtained, in the present work, we elucidate the geometrical parameters of this complex by computational methodologies. The optimization and vibrational investigation were carried out both in ethanolic solution and in gas phase. The computational results support the experimentally proposed geometries of the VIVO(chrys)2 complex, thus leading to the conclusion that the complex exists as conformers with trans-octahedral geometry in ethanolic solution and as conformers with cis-octahedral geometry in the solid state. The complex also exists as conformers with trans-octahedral geometry in aqueous media. The active species formed after dissolution in DMSO showed anticancer and antimetastatic behavior in human lung cell line A549 with moderate binding (Kaca. 105 M-1) to bovine serum albumin (BSA). The interaction through hydrogen bonding and van der Waals forces resulted in a spontaneous process. Site marker competitive experiments showed binding sites for chrysin mainly located in site II (subdomain IIIA) and in site I (subdomain IIIA) for the complex. FT-IR spectral measurements showed evidences of the alterations of protein secondary structure in the presence of chrysin and VIVO(chrys)2.

Assuntos

Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Flavonoides/farmacologia , Soroalbumina Bovina/metabolismo , Compostos de Vanádio/farmacologia , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Sítios de Ligação , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Humanos , Estrutura Molecular , Ligação Proteica , Conformação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Compostos de Vanádio/química , Compostos de Vanádio/metabolismo

RESUMO

Chronic exposure to aluminium (Al) can contribute to the progression of several neurological and neurodegenerative diseases. Al is a metal that promotes oxidative damage leading to neuronal death in different brain regions with behavior, cognition, and memory deficits. Chrysin is a flavonoid found mainly in honey, passion fruit, and propolis with antioxidant, anti-inflammatory, and cytoprotective properties. In this study, we used an integrated approach of in vitro and in vivo studies to evaluate the antioxidant and neuroprotective effects of chrysin against the neurotoxicity elicited by aluminium chloride (AlCl3). In in vitro studies, chrysin (5 µM) showed the ability to counteract the early oxidative stress elicited by tert-butyl hydroperoxide, an oxidant that mimics the lipid peroxidation and Fenton reaction in presence of AlCl3 as well as the late necrotic death triggered by AlCl3 in neuronal SH-SY5Y cells. In vivo studies in a mouse model of neurotoxicity induced by chronic exposure to AlCl3 (100 mg/kg/day) for ninety days then corroborated the antioxidant and neuroprotective effect of chrysin (10, 30, and 100 mg/kg/day) using the oral route. In particular, chrysin reduced the cognitive impairment induced by AlCl3 as well as normalized the acetylcholinesterase and butyrylcholinesterase activities in the hippocampus. In parallel, chrysin counteracted the oxidative damage, in terms of lipid peroxidation, protein carbonylation, catalase, and superoxide dismutase impairment, in the brain cortex and hippocampus. Lastly, necrotic cells frequency in the same brain regions was also decreased by chrysin. These results highlight the ability of chrysin to prevent the neurotoxic effects associated with chronic exposure to Al and suggest its potential use as a food supplement for brain health.

Assuntos

Encéfalo/efeitos dos fármacos , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Acetilcolinesterase/metabolismo , Cloreto de Alumínio , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Butirilcolinesterase/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Proteínas Ligadas por GPI/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Necrose , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Células THP-1

RESUMO

Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.

RESUMO

Brazilian propolis (AF-08) is a dietary supplement containing a variety of flavonoids. It is used worldwide as a folk medicine. Flavonoids and a diet of fruits and vegetables containing them have been shown to reduce the risk of cardiovascular diseases (CVDs). Most of CVDs are caused by arterial thrombus formation. A thrombus is formed by the interaction between adhesion and aggregation of platelets to damaged blood vessels and blood coagulation consisting of extrisic and intrinsic pathways. Platelet aggregation and blood coagulation are closely linked to thrombosis. Therefore, we evaluated the effectiveness of AF-08 or its component flavonoids against thrombosis by examining their inhibition of platelet aggregation and blood coagulation. Human platelet-rich plasma was incubated with serial dilutions of AF-08 for 10 min to assess its inhibitory effect on platelet aggregation caused by collagen. The inhibitory effect of AF-08 on blood coagulation was evaluated by the prothrombin time (PT) and activated partial thromboplastin time (APTT), which reflect the coagulation function of extrinsic and intrinsic pathways, respectively. AF-08 significantly inhibited collagen-induced platelet aggregation but not PT and APTT, indicating that AF-08 inhibited platelet aggregation but not blood coagulation. Among three flavonoids contained in AF-08, apigenin and chrysin obviously inhibited platelet aggregation but the inhibitory effect of kaempferol was less effective. The three flavonoids did not affect PT and APTT. The inhibitory activity of AF-08 on human platelet aggregation without affecting blood coagulation was suggested to be partially due to apigenin and chrysin. AF-08 may be effective in suppressing platelet-based arterial thrombus formation and reducing the risk of CVDs.

Assuntos

Agregação Plaquetária , Própole , Coagulação Sanguínea , Plaquetas , Colágeno , Humanos , Própole/farmacologia

RESUMO

Chrysin (5,7-dihydroxyflavone), a nutraceutical flavonoid present in diverse plants, has a backbone structure shared with the flavone backbone, with additional hydroxyl groups that confers its antioxidant properties and effects at the GABAA receptor complex. However, whether these effects are due to the hydroxyl groups is unknown. Here we report the effects of chrysin or the flavone backbone (1 mg/kg) in rats subjected to the elevated plus-maze and the locomotor activity test, as well as in the zebrafish evaluated in light/dark model. Chrysin, but not flavone, increased entries and time in the open arms of the elevated plus-maze, as well as time on white compartment of the light/dark model in zebrafish. These effects were comparable to diazepam, and were devoid of motor effects in both tests, as well as in the locomotor activity test. On the other hand, flavone decreased risk assessment in the light/dark test but increased rearing in the locomotor activity test in rats, suggesting effects threat information gathering; important species differences suggest new avenues of research. It is suggested that the specific effects of chrysin in relation to flavone include more of a mechanism of action in which in addition to its action at the GABAA/benzodiazepine receptor complex also could be involved its free radical scavenging abilities, which require specific research. Preprint: https://doi.org/10.1101/575514; Data and scripts:https://github.com/lanec-unifesspa/chrysin.

Assuntos

Ansiedade/tratamento farmacológico , Flavonas/uso terapêutico , Flavonoides/uso terapêutico , Locomoção/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Ansiedade/psicologia , Avaliação Pré-Clínica de Medicamentos/métodos , Flavonas/farmacologia , Flavonoides/farmacologia , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar , Peixe-Zebra

RESUMO

Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.

Assuntos

Ácido Glutâmico , Hipotireoidismo , Animais , Feminino , Flavonoides , Hipocampo/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , ATPase Trocadora de Sódio-Potássio/metabolismo

RESUMO

RATIONALE: The absence of ovarian hormones that is characteristic of natural and surgical postmenopause in women is frequently related to such disorders as depression and anxiety. Chronic treatment with the flavonoid chrysin was previously shown to exert antidepressant-like effects in rodents subjected to validate behavioral models. Chrysin has also been shown to have anxiolytic-like properties, but its antidepressant-like effects and mechanism of action in the absence of ovarian hormones remain unknown. OBJECTIVES: To compare the effects of the flavonoid chrysin with the effects of the neurosteroids progesterone and allopregnanolone on depression-like behavior in ovariectomized rats and evaluate the participation of γ-aminobutyric acid-A (GABAA) receptors in these actions. METHODS: Ovariectomized female Wistar rats were subjected to the locomotor activity test and forced swim test. The animals were assigned to eight treatment groups: vehicle, chrysin (1 mg/kg), progesterone (1 mg/kg), allopregnanolone (1 mg/kg), bicuculline (1 mg/kg), and pretreatment with bicuculline followed by chrysin, progesterone or allopregnanolone, respectively. After the treatments, the rats underwent the behavioral tests. RESULTS: Chrysin, progesterone, and allopregnanolone increased the latency to the first immobility and decreased the total immobility time in the forced swim test. The number of crossings and the time spent rearing and grooming decreased from the pretest to test sessions in the locomotor activity test. Chrysin, progesterone, and allopregnanolone only prevented the decreases in rearing and grooming. Bicuculline blocked the effects of chrysin, progesterone, and allopregnanolone in both behavioral tests. CONCLUSIONS: These results show that the GABA-binding site at GABAA receptors participates in the acute antidepressant-like effects of chrysin, similar to neurosteroids, in ovariectomized rats.

Assuntos

Depressão/fisiopatologia , Flavonoides/farmacologia , Neurônios GABAérgicos/metabolismo , Animais , Antidepressivos/farmacologia , Bicuculina/farmacologia , Depressão/tratamento farmacológico , Feminino , Flavonoides/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Locomoção/efeitos dos fármacos , Neuroesteroides , Ovariectomia , Pregnanolona/farmacologia , Progesterona/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos

RESUMO

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.

Assuntos

Antiulcerosos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Apoptose/genética , Caspase 3/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Etanol/toxicidade , Flavonoides/farmacocinética , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Inflamação , Interleucina-10/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/enzimologia

RESUMO

Chrysin (5,7-dihydroxyflavone) (Chrys) is a natural flavone extracted from many plants, and it has been proposed as a bioactive agent for cancer therapy. Nevertheless, its use is limited mainly due to its poor water solubility. Bovine serum albumin (BSA) is a water soluble, biocompatible and non-toxic protein with a promising application in lipophilic bioactive compound delivery. Moreover, BSA is heat sensitive, feature that could be used for producing self-assembled nanoparticle with tailor-made properties. In this contribution, we studied the formation of BSA nanoparticles (BSAnp) by thermal treatment at different conditions of temperature (70 °C/5 min and 85 °C/5 min), protein concentration (1.0-4.0%wt.) and aqueous medium pH values (9.0 and 11.0) in which it is known that BSA is found in different unfolded conformations. Binding of Chrys dissolved in dimethyl sulfoxide (DMSO) was studied by fluorescence titration experiments. Characterization of Chrys-loaded and unloaded BSAnp was performed in phosphate buffered saline (PBS) pH 7.4 by applying a set of complementary techniques: dynamic light scattering (DLS), size exclusion fast protein liquid chromatography (SEC-FPLC) and transmission electron microscopy (TEM). Different populations of BSAnp were obtained, which showed different diameters in the range of 1328 nm, ζ potentials around -10.0 mV, molecular weight in the range of 400-1000 kDa and spherical shape. Chrys encapsulation efficiency (EE. %) was also determined, and values between 44-84% were obtained, which mainly depended on the mode of Chrys binding and physicochemical BSAnp properties. Results highlight the ability of self-assembled BSAnp for Chrys vehiculization in an aqueous medium which could found potential application in antitumor therapies.

Assuntos

Antineoplásicos Fitogênicos/química , Portadores de Fármacos , Flavonoides/química , Nanopartículas/química , Soroalbumina Bovina/química , Animais , Soluções Tampão , Bovinos , Temperatura Alta , Concentração de Íons de Hidrogênio , Peso Molecular , Nanopartículas/ultraestrutura , Tamanho da Partícula , Solubilidade , Água/química

RESUMO

Abstract The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5 ± 0.20 mg/g), ethyl acetate (16.5 ± 0.37 mg/g) and n-butanol (8.85 ± 0.11 mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95 ± 0.04 and 1.04 ± 0.01 mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC = 0.42 mg/mL), Pseudomonas aeruginosa (MIC = 34.37 mg/mL), Paenibacillus apiarus (MIC = 4.29 mg/mL) and Paenibacillus thiaminolyticus (MIC = 4.29 mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625 µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.

Assuntos

Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Chenopodium ambrosioides/química , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação

RESUMO

The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5 ± 0.20 mg/g), ethyl acetate (16.5 ± 0.37 mg/g) and n-butanol (8.85 ± 0.11 mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95 ± 0.04 and 1.04 ± 0.01 mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC = 0.42 mg/mL), Pseudomonas aeruginosa (MIC = 34.37 mg/mL), Paenibacillus apiarus (MIC = 4.29 mg/mL) and Paenibacillus thiaminolyticus (MIC = 4.29 mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625 µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.(AU)

RESUMO

The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5±0.20mg/g), ethyl acetate (16.5±0.37mg/g) and n-butanol (8.85±0.11mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95±0.04 and 1.04±0.01mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC=0.42mg/mL), Pseudomonas aeruginosa (MIC=34.37mg/mL), Paenibacillus apiarus (MIC=4.29mg/mL) and Paenibacillus thiaminolyticus (MIC=4.29mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.

Assuntos

Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Chenopodium ambrosioides/química , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação

RESUMO

Abstract The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5 ± 0.20 mg/g), ethyl acetate (16.5 ± 0.37 mg/g) and n-butanol (8.85 ± 0.11 mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95 ± 0.04 and 1.04 ± 0.01 mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC = 0.42 mg/mL), Pseudomonas aeruginosa (MIC = 34.37 mg/mL), Paenibacillus apiarus (MIC = 4.29 mg/mL) and Paenibacillus thiaminolyticus (MIC = 4.29 mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625 µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.