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1.
Food Funct ; 9(11): 5891-5902, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30375606

RESUMO

Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate d-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.

2.
PLoS One ; 13(3): e0194069, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29538417

RESUMO

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC.


Assuntos
Berberina/análogos & derivados , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Animais , Berberina/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo
3.
Mol Med Rep ; 17(1): 789-800, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115625

RESUMO

Silymarin has been used in the treatment of a number of liver diseases for a long time, but its efficacy in preventing triptolide induced acute hepatotoxicity has not been reported previously. The present study aimed to assess the protective effect of silymarin against triptolide (TP)-induced hepatotoxicity in rats. Rats were orally administrated with silymarin (50, 100 and 200 mg/kg) for 7 days and received intraperitoneal TP (2 mg/kg) on the day 8. Hepatic injuries were comprehensively evaluated in terms of serum parameters, morphological changes, oxidative damage, inflammation and apoptosis. The results demonstrated that TP-induced increases in serum parameters, including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total cholesterol and γ-glutamyl transpeptidase, which were determined using a biochemical analyzer, and histopathological alterations and hepatocyte apoptosis as determined by hematoxylin and eosin and TUNEL staining, respectively, were prevented by silymarin pretreatment in a dose-dependent manner. TP-induced depletions in the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione S-transferase and catalase, and glutathione levels, were also significantly reversed by silymarin, as determined using specific kits. Additionally, silymarin dose-dependently exhibited inhibitory effects on malonaldehyde content in the liver. The production of proinflammatory cytokines was investigated using ELISA kits, and the results demonstrated that silymarin dose-dependently inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-1ß in the liver. To determine the mechanism of silymarin, western blot analysis was performed to investigate the protein expression of phosphorylated (p)-p38 and p-c-Jun N-terminal kinase (JNK) of the TNF-α induced inflammatory response and apoptotic pathways. Silymarin significantly blocked p38 and JNK phosphorylation and activation. Additionally, the expression of the proapoptotic proteins cytochrome c, cleaved caspase-3 and Bcl-2-associated X was also reduced following treatment with silymarin, as determined by ELISA, western blotting and immunohistochemistry, respectively. In conclusion, silymarin was demonstrated to dose-dependently protect rat liver from TP-induced acute hepatotoxicity, with the high dose (200 mg/kg) achieving a superior effect. This protective effect may be associated with the improvement of antioxidant and anti-inflammatory status, as well as the prevention of hepatocyte apoptosis. Therefore, silymarin may have the potential to be applied clinically to prevent TP-induced acute hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diterpenos/toxicidade , Fenantrenos/toxicidade , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Diterpenos/química , Compostos de Epóxi/química , Compostos de Epóxi/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/química , Substâncias Protetoras/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Silimarina/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-29250126

RESUMO

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-28424738

RESUMO

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPS via inhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

6.
Int J Mol Sci ; 18(3)2017 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-28245556

RESUMO

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-ß1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Bleomicina/farmacologia , Chrysanthemum/química , Extratos Vegetais/farmacologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Bleomicina/efeitos adversos , Dióxido de Carbono , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Citocinas/biossíntese , Modelos Animais de Doenças , Sinergismo Farmacológico , Fibrose , Extração Líquido-Líquido/métodos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Med Food ; 20(2): 180-188, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28146409

RESUMO

Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d50) of UDO obtained by ball milling was 6.56 µm. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.


Assuntos
Constipação Intestinal/tratamento farmacológico , Dendrobium/química , Laxantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Feminino , Gastrinas/metabolismo , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Laxantes/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Motilina/metabolismo , Extratos Vegetais/química , Substância P/metabolismo
8.
Rejuvenation Res ; 20(3): 231-243, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28056664

RESUMO

This study was designed to explore how supercritical fluid CO2 extract of Ligusticum chuanxiong Hort (CX) protects mouse liver and kidney from d-galactose-induced injury. The antioxidant capacity of CX was confirmed both in vitro and in vivo. The d-galactose-induced malondialdehyde increase was attenuated by CX, as well as the increase in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine level. In addition, the activities of antioxidant enzymes were markedly renewed, and the gene expressions of these enzymes were upregulated in CX groups. The results of histological analysis suggested that CX could effectively attenuate the d-galactose-induced structure damage. Furthermore, results of Western blotting analysis showed that CX significantly inhibited the upregulation of nuclear factor protein expression caused by d-galactose. In conclusion, CX could attenuate the liver and kidney injury in d-galactose-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response.


Assuntos
Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico , Rim/lesões , Ligusticum/química , Fígado/lesões , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Envelhecimento/patologia , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Ciclo-Oxigenase 2/metabolismo , Galactose , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Concentração Inibidora 50 , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Especificidade de Órgãos , Extratos Vegetais/química
9.
Artigo em Inglês | MEDLINE | ID: mdl-27847530

RESUMO

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is commonly used to treat kidney diseases in traditional Chinese medicine for its prominent anti-inflammatory effect and nourishing function to kidneys. In this study, aqueous extract of CS was assessed for its protective effect on UV-induced skin damage of mice. The chemical compositions of CS aqueous extract were determined by HPLC-ESI-MS/MS, in which 10 components were identified. During the experimental period, CS (0.9, 1.8, and 3.6 g/mL) was externally applied to shaved dorsal skins of mice prior to UV irradiation, daily for ten weeks. The results presented that CS (3.6 g/mL) apparently improved photodamaged skin appearance such as erythema, edema, and coarseness. The abnormal epidermal thickening was significantly reduced, and the dermal structures became more complete. The underlying protective mechanisms were associated with improving antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), downregulating inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2, and PGE2) expressions, recovering collagen density, and reducing matrix metalloproteinases productions. Sun protection factor of CS (3.6 g/mL) was 16.21 ± 0.03. Our findings for the first time demonstrated that CS had therapeutic effect on the photoaged skin. The results indicated that CS is a potential agent for photoprotective cosmetics.

10.
Food Funct ; 7(11): 4545-4555, 2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27714005

RESUMO

Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury. Oxidative stress and apoptosis play a vital role in the aging process. In this study, the antioxidant ability of polydatin (PD) was investigated using four established in vitro systems. An in vivo study was also conducted to investigate the possible protective effect of PD on d-gal-induced liver and brain damage. The results showed that PD had remarkable in vitro free radical scavenging activity on 2,2-diphenyl-1-picryl-hydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS+˙) radical ions, and hydroxyl and superoxide anions. Results in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably decreased the depression of body weight and organ indexes, reduced the levels of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated alterations in liver and brain histopathology. PD also significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity and T-AOC levels in the liver and brain. In addition, the levels of inflammatory mediators, such as TNF-α, IL-1ß and IL-6 in serum were markedly reduced after PD treatment. Western blotting results revealed that PD treatment noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase-3 protein expression in liver and brain. Overall, our findings indicate that PD treatment could effectively attenuate d-gal-induced liver and brain damage, and the mechanism might be associated with decreasing the oxidative stress, inflammation and apoptosis caused by d-gal. PD holds good potential for further development into a promising pharmaceutical candidate for the treatment of age-associated diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Encefalopatias/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Galactose/toxicidade , Glucosídeos/farmacologia , Estilbenos/farmacologia , Envelhecimento , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Encefalopatias/prevenção & controle , Citocinas , Relação Dose-Resposta a Droga , Glucosídeos/administração & dosagem , Glucosídeos/química , Fígado , Malondialdeído , Camundongos , Estrutura Molecular , Estresse Oxidativo , Estilbenos/administração & dosagem , Estilbenos/química
11.
Exp Gerontol ; 77: 76-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26929999

RESUMO

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.


Assuntos
Óleos Voláteis/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Pele/patologia , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Feminino , Hiperplasia/tratamento farmacológico , Malondialdeído/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Óleos Voláteis/farmacologia , Pele/enzimologia , Raios Ultravioleta
12.
Int Immunopharmacol ; 32: 55-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26800098

RESUMO

Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. The inflammatory cytokines in the BALF were determined by ELISA assay. Moreover, the expressions of p65 and phosphorylated p65 subunit of NF-κB, and Nrf2 in the nucleus in lung tissues were measured by Western blot analysis, and meanwhile the dependent genes of NF-κB and Nrf2 were assessed by RT-qPCR. The results showed that pretreatment with pogostone markedly improved survival rate, attenuated the histological alterations in the lung, reduced the MPO and MDA levels, decreased the wet/dry weight ratio of lungs, down-regulated the level of pro-inflammatory mediators including TNF-a, IL-1ß and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-κB regulated genes including TNF-α, IL-1ß and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-κB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/imunologia , Proteínas do Citoesqueleto/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Peroxidase/metabolismo , Transdução de Sinais/efeitos dos fármacos
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