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2.
J Diabetes Metab Disord ; 22(1): 205-215, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37255806

RESUMO

Background: Curcumin is active ingredient of turmeric The main purpose of this study is evaluating impact of curcumin on suger, hypoalgesia and inflammatory factors in diabetic mice. Materials and methods: Male mice divided into six groups of 6. One group as a negative and the other five groups injected with Streptozotocin (STZ) (200 mg/kg). Diabetic mice in each group given different treatments for twenty-one days.After that, blood sugar and neuroathy studies have been done and tissue samples the liver were studied for gene expression. Result: Curcumin reduced blood sugar, but the rate of hypoglycemia was significantly lower than metformin group P > 0.05, and the comparison of the synergistic effect of curcumin and metformin with metformin was not significant P > 0.05. Also, in neuropathy studies, the groups which recieved curcumin and metformin have shown a significant difference with diabetic group P < 0.01, Also, by evaluating inflammatory factors, there was a significant difference in the expression of TNF-a, IL-6 and NfkB, but there is no significant difference in the expression of Sirt1 P < 0.05. Conclusions: The analgesic effect of curcumin was quite evident, probably due to the significant impact of this herbal drug in reducing the expression of inflammatory genes NF-kB, IL6, and TNF-α. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01090-4.

3.
Life Sci ; 232: 116677, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31340166

RESUMO

AIMS: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence. MAIN METHODS: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA ß-gal expression. KEY FINDINGS: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA ß-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.


Assuntos
Senescência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Biomarcadores/metabolismo , Doxorrubicina/análogos & derivados , Glutationa Peroxidase/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
4.
Drug Chem Toxicol ; 42(2): 122-129, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29250976

RESUMO

Medicinal plants, as new drugs, are considered for treatment of insomnia, anxiety, depression, confusion, nausea, and vomiting symptoms. The current study aimed to evaluate the neuroprotective and antiemetic effects of Albizia. julibrissin Durazz. flower extract in the chickens. Emesis was induced by copper sulfate and ipecac (60 and 600 mg/kg, orally, respectively) and the methanolic extract (50, 100, and 200 mg/kg) were injected intraperitoneally (i.p.). Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC) content, and catalase activity as biomarkers of oxidative damage were evaluated in the brain mitochondria. All doses of extract showed significant (p < 0.001) antiemetic activity against induced emesis by copper sulfate and ipecac. Brain mitochondria function (by 50, 100, and 200 mg/kg of extract) were increased 48%, 85%, and 90% against emesis induced by ipecac and 32%, 18%, and 24% against emesis induced by copper sulfate, respectively. LPO and PC contents were significantly decreased after the administration of extract in emesis induced by copper sulfate and ipecac. A significant decrease (p < 0.01) of CAT activity was observed in the extract (200 mg/kg) group in emesis induced by copper sulfate in chickens brain mitochondria. The present study suggests that the extract had antiemetic effects against emesis induced by copper sulfate and ipecac in young chickens via peripheral and central mechanisms. Neuroprotective effect of the extract could be due to the increase in bioactive compounds, plasma antioxidants, or direct free radical scavenging that could prevent lipid and protein alteration and impede the formation of oxidative damage.


Assuntos
Albizzia/química , Antieméticos/farmacologia , Encéfalo/efeitos dos fármacos , Flores/química , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vômito/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Catalepsia/metabolismo , Galinhas , Sulfato de Cobre/farmacologia , Relação Dose-Resposta a Droga , Feminino , Flavonoides/análise , Ipeca/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fenóis/análise , Extratos Vegetais/química , Vômito/induzido quimicamente
5.
Bioorg Chem ; 75: 86-98, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28922629

RESUMO

Tubulin-targeting compounds have a broad anticancer spectrum and are an important class of chemotherapeutic agents. Due to the importance of 3-bromo-3,5-dimethoxyphenyl scaffold in the anticancer activity of microtubule inhibitors such as crolibulin (EPC2407), we introduced this functionality into the indole-derived chalcones. Thus, we describe here the synthesis and biological evaluation of new indole-based chalconoids as tubulin-targeting antiproliferative agents. The best result was obtained by compound 9b against A549 cell with IC50 of 4.3µg/mL, being more potent than the reference drug etoposide. Further biological evaluations revealed that compound 9b can inhibit tubulin polymerization and decrease the mitochondrial thiol content, resulting the induction of apoptosis in cancer cells. Docking studies with tubulin indicated that compound 9b could bind to the colchicine binding site.


Assuntos
Antineoplásicos/química , Colchicina/química , Indóis/química , Moduladores de Tubulina/química , Tubulina (Proteína)/química , Células A549 , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Colchicina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologia
6.
Cell Biol Toxicol ; 31(4-5): 231-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26493312

RESUMO

Nausea and vomiting are the most common symptoms in different diseases. Medicinal plants are considered as a reliable source of new drugs to control these symptoms. In this study, we evaluated the antiemetic and neuroprotective effects of the methanolic extract of Sambucus ebulus L. fruit and relationship between emesis (retching) and oxidative stress biomarkers in the mitochondria brain of young chickens. Emesis was induced by ipecac and copper sulphate (60 and 600 mg/kg, orally), respectively, and the methanolic extracts (50, 100, 200 mg/kg) were injected intraperitoneally (i.p.). The extract showed a significant antiemetic activity against ipecac and copper sulphate-induced emesis at all doses (p<0.001; percentages of retching inhibition 46, 96.5 and 83% against ipecac and 73, 79.5 and 69.2% against copper sulphate, respectively). Lipid peroxidation (LPO) was significantly decreased (p<0.001) at all doses of extract in retching induced by copper sulphate, and catalase (CAT) activity significantly increased (p<0.05) in the extract (50 mg/kg) and metoclopromide groups in retching induced by ipecac in the chickens' brain mitochondria. Protein carbonyl (PC) contents significantly (p<0.05) decreased only in extract (100 mg/kg) group in retching induced by ipecac. Mitochondria function (MTT assay) significantly increased by extract (100 mg/kg) as compared to control group in retching induced by ipecac. The results of this study suggests that the extract has protective effects, possibly by central and peripheral mechanisms, and neuroprotective effect by increasing plasma antioxidants or scavenging of free radicals induced by retching. It seems that extract could prevent protein modification and improve oxidative stress in the early stages.


Assuntos
Antieméticos/farmacologia , Náusea/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sambucus/química , Vômito/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Galinhas , Modelos Animais de Doenças , Feminino , Frutas/química , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Náusea/metabolismo , Estresse Oxidativo/fisiologia , Vômito/metabolismo
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