Paeoniflorin ameliorates lipopolysaccharide‐induced acute liver injury by inhibiting oxidative stress and inflammation via SIRT1/FOXO1a/SOD2 signaling in rats

Abstract

Acute liver injury (ALI) is a poor prognosis and high mortality complication of sepsis.Paeoniflorin (PF) has remarkable anti-inflammatory effects in different disease models. Here, we explored the protective effect and underlying molecular mechanisms of PF against lipopolysaccharide (LPS)-induced ALI. Sprague-Dawley rats received intraperitoneal (i.p.) injection of PF for 7 days, 1 h after the last administration, and rats were injected i.p. 10 mg/kg LPS. PF improved liver structure and function, reduced hepatic reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. Western blot analysis suggested that PF significantly inhibited expression of inflammatory cytokines (TNF-α, IL-1β, and IL-18) and inhibited activation of the NLRP3 inflammasome. PF or mitochondrial ROS scavenger (mito-TEMPO) significantly improved liver mitochondrial function by scavenging mitochondrial ROS (mROS), restoring mitochondrial membrane potential loss and increasing level of ATP and enzyme activity of complex I and III. In addition, PF increased expression of sirtuin-1 (SIRT1), forkhead box O1 (FOXO1a) and manganese superoxide dismutase (SOD2), and increased FOXO1a nuclear retention. However, the inhibitor of SIRT1 (EX527) abolished the protective effect of PF. Taken together, PF promotes mROS clearance to inhibit mitochondrial damage and activation of the NLRP3 inflammasome via SIRT1/FOXO1a/SOD2 signaling.

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition

“…Excessive ROS formation, disruption of the prooxidant/antioxidant balance and inflammation are critical events in the pathogenesis of liver damage. 29 Altered levels of CORT are known to enhance the toxicity of oxygen radicals by increasing the basal levels of ROS. 30 In the present study, hepatic ROS, and serum and hepatic levels of the stress-related hormone CORT in CUMS mice were concurrently reversed by HT treatment.…”

Broad bean (Vicia faba L.) caused abnormal lipid metabolism in grass carp (Ctenopharyngodon idellus) liver: Insight from the gut microbiota–liver axis

“…The absence of these symbiotic beneficial bacteria resulted in lower levels of SCFA, as demonstrated by our results. Several studies had shown that increased LPS in the gut caused intestinal inflammation and disrupted the intestinal barrier, after which LPS entered the circulation, causing oxidative stress and disrupting lipid metabolism in the liver (Li et al., 2022; Zheng & Wang, 2021). In our study, broad bean increased LPS and decreased SCFA levels in the gut, which were consistent with the observation of inflammatory responses and impaired intestinal barriers in the intestinal tract of CGC.…”

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

“…Oxidative stress contributes to inflammation and organ injury during sepsis ( Kumar et al, 2022 ). Various studies have disclosed that inhibition of oxidative stress ameliorates sepsis and/or sepsis-induced multiple organ dysfunctions, including lung, liver, kidney, heart, etc ( Gong et al, 2022 ; He et al, 2022 ; Li X. et al, 2022 ; Li L. et al, 2022 ). The data of our study revealed that MALT1 overexpression increased the levels of serum proinflammatory cytokines, including TNF-α, IL-6, and IL-1β, while MALT1 knockdown decreased these proinflammatory cytokines.…”