Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway

Abstract

The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway.

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

“…In addition, the level of NRF2 in the cytoplasm was significantly downregulated after OTA treatment, and the level of NRF2 in the cytoplasm was even lower after ASX pretreatment. This finding is consistent with previous research [55]. Therefore, our results confirm that ASX promotes the transfer of NRF2 from the cytoplasm to the nucleus, resulting in enhanced expression of its downstream targets NQO1, HO1, γ-GCS, and GSH-Px, which improves the redox balance, increases the protection of mouse kidney cells, and ultimately improves the body's antioxidant capacity (Figure 8).…”

Quercetin Protects against Lipopolysaccharide-Induced Intestinal Oxidative Stress in Broiler Chickens through Activation of Nrf2 Pathway

“…Quercetin could effectively inhibit manganese-induced oxidative stress and inflammatory response in neuraltumor epithelialcells (SK-N-MC) in Sprague-Dawley rats though activating HO-1/Nrf2 and inhibiting the NF-κB pathway [31]. Additionally, quercetin could improve mitochondrial function by promoting the translocation of Nrf2 from the cytoplasm to the nucleus and activating the Nrf2 signaling pathway [32,33]. In our study, quercetin promoted Nrf2 levels and translocation, and it increased Nrf2 downstream genes levels (HO-1, NQO1, and SOD), suggesting that quercetin inhibits LPS-induced intestinal oxidative stress through the Nrf2 signaling pathway.…”

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

“…In response to oxidative stress, Nrf2 promotes the expression of a wide range of antioxidant genes through translocating into the nucleus and binding to antioxidant response element (ARE), eventually leading to regulate the transcription of downstream target genes, 37 such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), GSH-Px, and SOD. Nrf2/ARE antioxidative signaling pathway has been considered to protect brain against cerebral ischemia injury, 37 traumatic brain injury, 38 intracerebral hemorrhage, 39 Pakinson's disease 40 , and also SAH. 41 Nrf2 and the downstream target genes like HO-1, NQO1 and glutathione S-transferase-a1 was demonstrated to protect brain subjected to SAH via the Figure 4.…”