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1.
Int Immunopharmacol ; 110: 108970, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35792271

RESUMO

Tannic acid (TA) is a natural compound present abundantly in fruit such as grapes and green tea. In this study, we have evaluated the therapeutic efficacy of TA against Lipopolysaccharide (LPS)-induced oxidative stress-mediated memory impairment, neuroinflammation, insulin signaling impairment, and Amyloid Beta (Aß) deposition in adult male mice. The LPS was administered once per week and TA twice a week to adult male mice for three months consecutively. Behavioral studies were performed using different behavioral models such as balance beam, novel object recognition (NOR), Morris water maze (MWM), and Y-maze tests. The protein expression of different mediators such as TNF-α, p-JNK, pIRS636, BACE1, APP, and Aß was evaluated through western blot and immunofluorescence staining techniques. Biochemical assays were carried out to assess the antioxidant activities of TA. The computational study was conducted to predict the binding mode of TA with target sites of TNF-α. Behavioral studies showed that the TA-treated mice exhibited gradual memory improvement. TA significantly inhibited BACE1 activity and reduced production and accumulation of Aß in the hippocampus of mice brains. Moreover, the TA significantly inhibited LPS-induced ROS production and enhanced the glutathione levels. Furthermore, we have shown via the computational method for the first time that TA inhibits LPS-triggered TNF-á½° and its downstream signaling to reduce AD pathology including memory impairment, neuroinflammation, insulin signaling impairment, and Aß deposition in adult mice. Taken together our current study demonstrates that TA is a potential candidate for the abrogation of LPS-induced neurotoxicity and AD pathology in rodent's models.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Insulinas , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/efeitos adversos , Ácido Aspártico Endopeptidases/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Insulinas/efeitos adversos , Lipopolissacarídeos/farmacologia , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Camundongos , Taninos/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo
2.
Pak J Pharm Sci ; 34(5(Supplementary)): 1861-1866, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34836851

RESUMO

Citrus limetta is well known for its anti-inflammatory, antimicrobial, antifungal, antidiabetic and antioxidant properties. Methanolic extract of Citrus limetta (MECL) was used to assess cellular and humoral immune responses in mice by carrying out cyclophosphamide-induced neutropenia, delayed-type hypersensitivity (DTH), carbon clearance assay, haemagglutination assay (HA) and mice lethality assay. Methanolic extract of Citrus limetta peel was administered orally to mice in two doses 200mg/kg and 400mg/kg.The extract treated groups showed improvement in neutropenia induced by cyclophosphamide and improvement in the WBC profile. Skin thickness was significantly (P<0.05) higher in 200mg/kg and 400mg/kg groups in comparison to control in DTH. The phagocytic index was significantly (P<0.05) more in 400mg/kg group in carbon clearance assay. Mice were vaccinated with hemorrhagic septicemia vaccine before challenge with Pasteurella multocida for mice lethality test. Percentage mortality was decreased in 400mg/kg treated group in comparison to negative control Antibody titre response to sheep red blood cells was significantly (P<0.05) higher with dose 400mg/kg in HA. Results suggested the effectiveness of the methanolic extract of Citrus limetta as an immunostimulating agent.


Assuntos
Citrus/química , Frutas/química , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anticorpos Antibacterianos/análise , Carbono/metabolismo , Ciclofosfamida , Contagem de Leucócitos , Metanol , Camundongos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Infecções por Pasteurella/imunologia , Infecções por Pasteurella/prevenção & controle , Pasteurella multocida/imunologia , Fagocitose/efeitos dos fármacos , Ovinos , Pele/efeitos dos fármacos , Solventes
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