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1.
Environ Sci Pollut Res Int ; 29(53): 80910-80925, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35729379

RESUMO

The aim of the current study was to assess the potential cardiopreventive effect of the methanolic extract of S. molle L. (MESM) on isoproterenol-induced infarction in rats. The biomolecules content was evaluated using HPLC-DAD-ESI-QTOF-MS/MS analysis. On the 29th and 30th days, two successive injections of isoproterenol (ISO) were given to Wistar rats to provoke myocardial infarction following pretreatment with either MESM (60 mg/kg b.w) or Pidogrel (Pid; 2 mg/kg b.w.). A total of sixteen phenolics were identified with masazino-flavanone as the most prevalent compound (1726.12 µg/g dm). Results showed that MESM offered cardioprevention by normalizing the ST segment and reducing the elevated cardiac risk parameters. The altered lipid biomarkers together with the plasma ionic levels were improved. Additionally, MESM inhibited the cardiac oxidative stress generated by ISO injection though enhancing antioxidant enzymes (GSH, CAT, SOD and GPX) which reduced lipid peroxidation and protein oxidation. MESM reduced myocardial apoptosis by significantly repressing mRNA expressions of Caspase-3 and Bax, with an upregulated Bcl-2 expression. Moreover, MESM reduced DNA fragmentation as well as the infarct size observed by TTC staining. In addition, MESM exhibited an antifibrotic effect by downregulating TGF-1ß expression and reducing collagen deposition in myocardial tissue, as confirmed by Trichrom Masson analysis. The histopathological findings revealed less muscle separation and fewer inflammatory cells in the ISO + MESM-treated rats. Results of the docking simulation indicated that catechin in MESM was inhibitory mainly due to hydrogen bonding interactions with PDI, ACE and TGF-ß1 proteins which could highlight the antithrombotic and antifibrotic capacity of MESM.


Assuntos
Anacardiaceae , Catequina , Infarto do Miocárdio , Extratos Vegetais , Animais , Ratos , Anacardiaceae/química , Antioxidantes/metabolismo , Proteína X Associada a bcl-2/metabolismo , Biomarcadores/metabolismo , Caspase 3/metabolismo , Catequina/metabolismo , Fibrinolíticos/metabolismo , Frutas/química , Isoproterenol/toxicidade , Lipídeos/toxicidade , Simulação de Acoplamento Molecular , Infarto do Miocárdio/induzido quimicamente , Miocárdio/metabolismo , Estresse Oxidativo , Extratos Vegetais/farmacologia , Ratos Wistar , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Espectrometria de Massas em Tandem , Fator de Crescimento Transformador beta1/metabolismo
2.
Phytother Res ; 35(11): 6170-6180, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33908658

RESUMO

It is widely known that breast cancer cells eventually develop resistance to hormonal drugs and chemotherapies, which often compromise fertility. This study aimed to investigate the effect of the flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl (KARP), on 1) the viability of MCF-7 breast cancer cells and 2) ovarian function in rats. A dose-dependent decrease in MCF-7 cell survival was observed, and the IC50 value was found to be 48 µg/ml. Cells in the control group or those exposed to increasing concentrations of KARP experienced a similar generation of reactive oxygen species and induction of apoptosis. For the rats, estradiol levels correlated negatively to KARP dosages, although a recovery was obtained at administration of 30 mg/kg per day. Noteworthily, when compared against the control, this dosage led to significant increases in mRNA levels for CYP19, CYP17a, CCND2, GDF9, and INSL3 among the treatment groups, and ER1 and ER2 mRNA levels decreased in a dose-dependent manner. KARP shows great promise as an ideal therapy for breast cancer patients since it induced apoptosis and autophagy in cancerous cells without harming fertility in our animal model. Future investigations on humans are necessary to substantiate these findings and determine its efficacy as a general line of treatment.


Assuntos
Neoplasias da Mama , Flavonoides , Animais , Apoptose , Aromatase/genética , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Ciclina D2 , Feminino , Fator 9 de Diferenciação de Crescimento/genética , Humanos , Insulina/genética , Quempferóis/farmacologia , Proteínas/genética , Ratos , Esteroide 17-alfa-Hidroxilase/genética
3.
Toxicol Mech Methods ; 29(1): 26-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30064281

RESUMO

Previous studies have brought to light the toxic effect of cerium chloride (CeCl3) but very little is known about the oxidative brain injury caused by this metal. Medical plants have a well-recognized role in the management of damage caused by pollutants such as CeCl3. Syzygium aromaticum, a potent natural source of bioactive compounds and rich in secondary metabolites, has a broad range of biological functions. The aim of this study is to investigate the capacity of Syzygium aromaticum ethanol extract (ESA) to improve the adverse effects of CeCl3 in the brain tissue. Adult mice were exposed to CeCl3 (20 mg/kg body weight [BW]), with or without ESA, for 60 days. We investigate mice's behavior, damages of cholinergic system and oxidative stress parameters in mice brain. In the present study, in vitro test confirmed that ESA has antioxidant capacity attributed to the presence of flavonoids, polyphenols, and tannins contents. In vivo study showed that CeCl3 caused brain injuries manifested in memory impairment, increase in acetylcholinesterase activity, oxidative stress biomarkers (lipid, proteins, enzymatic and non-enzymatic antioxidant systems), and histopathological alteration in brain tissue. Addition of ESA repaired memory impairment, decreased acetylcholinesterase activity, restored oxidative state, and prevented histopathological alteration. In conclusion, the experimental results showed the protective effects of ethanol extract of Syzygium aromaticum against cerium-induced brain damage.


Assuntos
Encéfalo/efeitos dos fármacos , Cério/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Syzygium/química , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Camundongos , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação
4.
Environ Sci Pollut Res Int ; 25(20): 19555-19565, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29732511

RESUMO

Cerium chloride (CeCl3) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl3, 20 mg/kg BW) along with Curcuma longa extract, administrated by gavage (100 mg/kg BW), into mice for 60 days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl3-treated mice. In addition, CeCl3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl3-treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl3-induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl3-damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl3-induced damage in the brain.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cério/toxicidade , Poluentes Ambientais/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Encéfalo/enzimologia , Curcuma , Masculino , Camundongos , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação
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