RESUMO
Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.
Assuntos
Proteína HMGB1 , NF-kappa B , Animais , Antidepressivos/farmacologia , Depressão , Furanos , Glucosídeos , Camundongos , Receptores Tipo I de Fatores de Necrose Tumoral , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfaRESUMO
Toxoplasmosis is a parasitic zoonosis with the highest incidence in humans. Severe lesions due to acute toxoplasmosis have been recorded in the visceral organs including the liver, where hepatocytes and Kupffer cells are important innate immune cells. Arctigenin (AG) is a bioactive ingredient of Arctium lappa L. and increasing evidence suggests that AG exhibits anti-oxidant, anti-inflammatory and anti-Toxoplasma gondii (T. gondii) effects. However, the role of AG in acute liver damage induced by T. gondii infection remains unclear. In this study, we analyzed the effects of AG against T. gondii-induced liver damage by establishing an in vitro infection model using a murine liver cell line (NCTC-1469 cells) and an in vivo mouse model with acute T. gondii infection of virulent RH strain. In the current study, AG effectively attenuated hepatocytes apoptosis and inhibited the reproduction of T. gondii. The results of in vitro and in vivo studies showed that AG significantly reduced alanine aminotransferase/aspartate aminotransferase activities and lessened pathological damage of liver. Moreover, AG suppressed T. gondii-induced inducible nitric oxide synthase production. AG also attenuated liver inflammation by inhibiting T. gondii-induced activation of the high-mobility group box1/toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway. These findings demonstrated that AG exhibited prominent hepatoprotective activities in toxoplasmic liver injury with anti-inflammatory effects by inhibiting the HMGB1/TLR4/NF-κB signaling axis. Thus, this study provides the basis for the development of new drugs to treat toxoplasmic hepatitis.
Assuntos
Furanos/uso terapêutico , Lignanas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Toxoplasmose/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Linhagem Celular , Feminino , Furanos/farmacologia , Proteína HMGB1/imunologia , Lignanas/farmacologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/imunologia , Toxoplasma , Toxoplasmose/imunologiaRESUMO
Toxoplasma gondii (T. gondii) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti-T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii-infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii-induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii. AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.
RESUMO
Previously, we have shown that the fatty acid composition of Altay sheep tail fat is of reasonable value and is suitable for further development of possible commercial products. Changes in lipids of Altay sheep tail fat during 50 days of 4°C refrigerated storage were investigated. Lipid oxidation and lipolysis occurred during the storage. The pH showed a continually decreased from first day to the end of the storage (p < 0.05). The lipid oxidation was determined by peroxide value (PV) and thiobarbituric acid-reactive substances (TBARS). The increase PV was observed in Altay sheep fat up to 24 days of storage and decreased from then to the day 30 (p < 0.05). The increase in TBARS was significantly throughout the refrigerated storage (p < 0.05). The changes of the fatty acids identified by GS-MS demonstrated that saturated fatty acids increased from 43.6% to 56.3% and that polyunsaturated fatty acids and monounsaturated fatty acids decreased form 51.2% to 43.7% and from 2.4% to 2.1%, respectively. The content of the functional fatty acids except (C18:2 n-9), started to decrease after 20 days of storage. Those changes indicated that lipid oxidation occurred in Altay sheep tail fat during a long time of low temperature storage. In addition, the good correlation between PV/TBARS values and changes of individual fatty acids could be used as an indicator to monitor the changes of the unsaturated fatty acid during the development process of Altay sheep tail fat-related commercial products.
Assuntos
Ácidos Graxos/química , Peroxidação de Lipídeos , Triglicerídeos/química , Animais , Concentração de Íons de Hidrogênio , Lipólise , Peróxidos/análise , Refrigeração , Ovinos , Temperatura , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Lectins are the tools for the determination of sugar chain structure. Recently, lectin arrays have become a popular new technology; therefore, lectins with specific sugar-binding properties are required. The objective of the study was to isolate a novel lectin from Pleurotus ferulae mushrooms and characterize its various biological activities. A novel lectin was extracted with deionized water, precipitated from the aqueous extract using 75% saturated (NH4)2SO4, and subjected on DEAE-cellulose followed by affinity chromatography on sepharose-6B. The activity was tested using hemagglutination assays, and carbohydrate-binding specificity was determined by glycan microarray analysis. Its effects on the mitogenic activity of mouse splenocytes were determined by MTT assay. The novel lectin was adsorbed on ion-exchange chromatography DEAE-cellulose and shown as a band with the molecular mass of 17.5 kDa on a SDS-PAGE and as a single 35.0-kDa peak in gel filtration on Superdex G-75. The hemagglutinating activity of the lectin was inhibited by D-glucose, lactose, D-galactose, and galactosamine. The lectin was stable on 60°C. The hemagglutinating activity of lectin was reduced by 50% at 70°C. At 80°C, it was further reduced to 6.25% of its original activity. The hemagglutinating activity was the highest at pH 6-9. Moreover, its hemagglutinating activity was inhibited by Mg2+ and Ca2+ ions. The lectin isolated from P. ferulae in the current study possessed highly potent hemagglutinating and proliferative activities toward mouse splenocytes.