ABSTRACT
Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/423533v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1be5b38org.highwire.dtl.DTLVardef@56e061org.highwire.dtl.DTLVardef@1a52040org.highwire.dtl.DTLVardef@1e86751_HPS_FORMAT_FIGEXP M_FIG C_FIG SummaryInfections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show a number of non-neural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood, so we developed three models to investigate the impact of neuroinflammation on muscle performance. We found that bacterial infection, COVID-like viral infection, and expression of a neurotoxic protein associated with Alzheimer' s disease promoted the accumulation of reactive oxygen species (ROS) in the brain. Excessive ROS induces the expression of the cytokine Unpaired 3 (Upd3) in insects, or its orthologue IL-6 in mammals, and CNS-derived Upd3/IL-6 activates the JAK/Stat pathway in skeletal muscle. In response to JAK/Stat signaling, mitochondrial function is impaired and muscle performance is reduced. Our work uncovers a brain-muscle signaling axis in which infections and chronic diseases induce cytokine-dependent changes in muscle performance, suggesting IL-6 could be a therapeutic target to treat muscle weakness caused by neuroinflammation.
ABSTRACT
Objective The aim of this study was to investigate the effects of hesperidin ( HDN) on antioxidant ac-tivity in mice.Methods HDN scavenging free radicals was detected by spectrophotometry, inhibition of mitochondrial swelling was detected by pyrogallol autoxidation, and erythrocyte hemolysis was detected by Fe2+phenanthroline.The mice were fed with HDN at different concentrations (0, 80, 160, 320 mg/kg) by gastric gavage for 12 days.ELISA and spec-trophotometric methods were used to assay the amount of MDA in mouse liver and kidney tissues and the activity of antioxi-dant enzymes ( SOD, CAT, GSH-PX) , and the antioxidant enzyme gene mRNA expression was analyzed by RT-PCR.Re-sults Compared with the control group, the radical (· OH, O2 -· , DPPH· ) clearance rate was significantly increased in the HDN groups.There was a significant decrease of oxidative hemolysis of erythrocytes and mitochondrial swelling in vitro. MDA content in the mouse liver and kidney tissues and serum showed a decrease, and the activity of antioxidant enzymes ( SOD, CAT, GSH-PX) in the HDN group was significantly higher than that in the control group.There was an up-regula-tion of mRNA expression of antioxidant enzyme in mouse liver and kidney tissues.Conclusions The results showed that HDN can eliminate free radicals, reduce cell oxidative damage caused by free radicals, inhibit superoxide production, up-regulate antioxidant enzyme gene expression and enhance their enzyme activity, thus showing a good antioxidant effect.
ABSTRACT
Objective The purpose of this study was to investigate the mechanism of action of polypeptide extracts of Eupolyphaga sinensis Walker ( ESW) against oxidative aging.Methods Mice were intraperitoneally injected D-galac-tose for consecutive 20 days to establish an aging mouse model.The model mice were administered with different doses of ESW polypeptide (0, 40, 80, 160 mg/kg/d).The normal activity, movement and anti-stress ability of the mice were ob-served.The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) in blood and different tissues and the content of glutathione ( GSH) and malondialdehyde ( MDA) of the aging mice were assessed by xanthin oxidase activity measurement and spectrophotometry, respectively.The expression of nuclear factor erythroid 2-re-lated factor 2 (Nrf2) in Caco-2 cells was detected by immunofluorescence.Results Comparing the control and polypep-tide groups, there were significant decreases of body weight gain, organ indexes, anti-stress ability and activity capacity, the activity of SOD, CAT, GSH-PX and the content of GSH, and an increase of the content of MDA in blood and different tissues in the aging mice.With the increasing dose of polypeptide extracts of ESW, the body weight gain, organ indexes of the liver, spleen and kidney were significantly increased, the static and dynamic exercise time was prolonged in the poly-peptide group, and their abilities of hypoxia tolerance and heat tolerance were close to that of normal controls.The SOD, CAT, GSH-PX activity and GSH level in blood and different tissues were significantly increased, but MDA content de-creased.The expression of Nrf2 in Caco-2 cell nuclei was significantly increased in the polypeptide group, close to that of the positive control group.Conclusions The results of our study show that polypeptide extracts of ESW improve the anti-stress and antioxidative capacity in D-galactose-induced mouse models of oxidative aging by initiating Nrf2-ARE antioxidant signaling pathway, therefore, delay the oxidative aging in mice.
