RESUMEN
Food intake influences neurofunction via the gut microbiota-brain axis. Monounsaturated fatty acid (MUFA) consumption is highly associated with neuroprotection; the mechanism behind the effects of olive oil and camellia oil on gut microbiota remains unclear. In this study, the objective was to compare the neuroprotective role of oleic acid-rich camellia oil and olive oil against AlCl3-induced mild cognitive impairment (MCI) in rats. Morris water maze tests revealed that learning and memory capacities improved in AlCl3-induced rats subjected to camellia oil administration better than olive oil treatment. Moreover, the results showed that the camellia oil- and olive oil-treated AlCl3-induced rat groups had significantly reduced oxidative stress and inflammatory cytokines. Notably, Spearman correlation analysis indicated that the inflammatory cytokines negatively correlated with the microbial strains (Bacteroides pectinophilus_group and Blautia) in response to camellia oil administration. Furthermore, Ruminococcaceae_UCG014 abundance was significantly enhanced by camellia oil intake, which was highly positively associated with antioxidant activity expression. In conclusion, the novel data suggest that the outcomes of camellia oil consumption were superior to those of olive oil intake as camellia oil may have a beneficial effect on MCI protection and improvement through the gut microbiota-brain communication.
Asunto(s)
Camellia , Disfunción Cognitiva , Microbioma Gastrointestinal , Animales , Encéfalo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Citocinas/farmacología , Aceite de Oliva/farmacología , Aceites de Plantas/farmacología , RatasRESUMEN
Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18ß-Glycyrrhetinic acid (18ß-GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18ß-GA on sRAGE secretion via TRPC channels in high glucose (HG)-induced THP-1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide-adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18ß-GA showed the dramatic effects similar to Pyr3 or 2-aminoethyl diphenyl borinate inhibitors and effectively reversed HG-elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18ß-GA provides a potential implication to diabetes mellitus and its complications.
Asunto(s)
Glucosa/antagonistas & inhibidores , Ácido Glicirretínico/análogos & derivados , Glycyrrhiza/química , Hipoglucemiantes/farmacología , Receptor para Productos Finales de Glicación Avanzada/genética , Canales Catiónicos TRPC/genética , Canal Catiónico TRPC6/genética , Compuestos de Boro/farmacología , Calcio/metabolismo , Regulación de la Expresión Génica , Glucosa/toxicidad , Ácido Glicirretínico/aislamiento & purificación , Ácido Glicirretínico/farmacología , Humanos , Hipoglucemiantes/aislamiento & purificación , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Pirazoles/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de Señal , Células THP-1 , Canales Catiónicos TRPC/antagonistas & inhibidores , Canales Catiónicos TRPC/metabolismo , Canal Catiónico TRPC6/antagonistas & inhibidores , Canal Catiónico TRPC6/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismoRESUMEN
Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.