Anti-Inflammatory and Antioxidant Effect of Eucommia ulmoides Polysaccharide in Hepatic Ischemia-Reperfusion Injury by Regulating ROS and the TLR-4-NF-κB Pathway

Abstract

Eucommia ulmoides polysaccharide (EUP) has been shown to have anti-inflammatory and antioxidant effects. However, the mechanism underlying these effects has rarely been reported, and whether EUP can reduce liver injury in hepatic ischemia-reperfusion injury (HIRI) has not been reported. In this study, 40 Sprague-Dawley (SD) rats were randomly divided into 5 groups: the sham group, ischemia-reperfusion (I/R) group, and three EUP pretreatment groups (320 mg/kg, 160 mg/kg, and 80 mg/kg). SD rats were pretreated with EUP by gavage once a day prior to I/R injury for 10 days. Except for the sham group, blood flow in the middle and left liver lobes was blocked in all the other groups, resulting in 70% liver ischemia, and the ischemia and reperfusion times were 1 h and 4 h, respectively. Ischemic liver tissue and serum were obtained to detect biochemical markers and liver histopathological damage. Compared with the I/R group, after EUP pretreatment, serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1β levels were significantly decreased, malondialdehyde levels in liver tissues were significantly decreased, superoxide dismutase levels were significantly increased, and the area of liver necrosis was notably reduced. To understand the specific mechanism involved, we determined the levels of Toll-like receptor- (TLR-) 4-nuclear factor-kappaB (NF-κB) pathway-associated proteins in vivo and in vitro. The data showed that EUP can reduce liver damage by decreasing ROS levels and inhibiting TLR-4-NF-κB pathway activation and may be a promising drug in liver surgery to prevent HIRI.

Eucommia ulmoides Polysaccharides Attenuate Rabbit Osteoarthritis by Regulating the Function of Macrophages

“…It is a powerful immune enhancer (Feng et al, 2016), which can regulate the immune behavior of macrophages and make them develop in the direction of antiinflammatory. In addition, EUP also has anti-inflammatory and antioxidant properties, as well as inhibits osteoclasts and promotes osteogenic effects (Deng et al, 2019;Gao et al, 2020). In view of the powerful ability of EUP to regulate immunity, it is of great significance to explore its effect on osteoarthritis and its possible mechanism.…”

Dexmedetomidine Protects against Hepatic Ischemia-Reperfusion Injury by inhibiting Endoplasmic Reticulum Stress and Cell Apoptosis in Rats

“…The experimental protocol was approved by the Agricultural University of Hebei Ethical Committee, Baoding, China. 70% Hepatic I-R model was performed according to previous studies [21] . An atraumatic clip was applied to the portal vessels to induce ischemia of the middle and left hepatic lobes under iso urane anesthesia.…”

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

“…In L02 cells transfected with TLR4 overexpression plasmid, polysaccharide (8 μg/ml) of E. ulmoides significantly inhibited the increasing expression of TLR4, MyD88, P-p65, and P-IκB-α proteins. The mechanisms referring to the inhibition TLR-4/NF-κB pathway activation by reducing HMGB1 release inhibition [ 45 ].…”

“…Over the past two decades, in complement to the above assessment of antioxidant activities, the favorable antioxidant activities of E. ulmoides has been demonstrated in biological in vivo experiments, with validity against oxidative stress in gastric mucosal injury, chronic hepatotoxicity, diabetes complications, lead-induction, obesity, I/R induced renal and hepatic toxicity etc. [ 45 , 60 – 65 ]. Aqueous extract of E. ulmoides leaves has been demonstrated been therapeutic on water and VC-deficient diets induced gastric mucosal injury pigs.…”

“…The treatment (100 mg/kg) decreased the oxidized glutathione (GSSG) concentration and GSSG/GSH ratio and it increased the protein expressions of nuclear Nrf2 and Keap1, mRNA expression of HO-1, NQO-1, GCLC in the small intestinal mucosa [ 73 ]. In blood flow blocking-induced hepatic I/R injury rats, polysaccharide (80, 160 and 320 mg/kg) of E. ulmoides decreased ROS, MDA levels and increased SOD levels in liver [ 45 ]. In rabbits with I/R induced renal toxicity, the polysaccharides (300 and 600mg/kg) increased SOD, CAT, GSH-Px and GR activities whereas decreased MDA content in the kidney [ 60 ].…”