Icariin Alleviates Escherichia coli Lipopolysaccharide-Mediated Endometritis in Mice by Inhibiting Inflammation and Oxidative Stress

Abstract

Icariin (ICA) is a naturally occurring phytochemical agent primarily extracted from Epimedium Brevicornum Maxim (Family Berberidaceae) with a broad spectrum of bioactivities. Endometritis is a uterine disease that causes enormous losses in the dairy industry worldwide. In this study, anti-inflammatory and anti-oxidant properties of ICA were investigated against lipopolysaccharide (LPS)-induced endometritis in mice to investigate possible underlying molecular mechanisms. Sixty heathy female Kunming mice were randomly assigned to four groups (n = 15), namely control, LPS, LPS + ICA, and ICA groups. The endometritis was induced by intrauterine infusion of 50 µL of LPS (1 mg/mL). After 24 h of onset of LPS-induced endometritis, ICA groups were injected thrice by ICA intraperitoneally six hours apart. Histopathological examination, enzyme linked immunosorbent assay (ELISA), real time quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry were used in this study. Histological alterations revealed that ICA markedly mitigated uterine tissue injury caused by LPS. The results showed that the ICA inhibited the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and boosted the production of anti-inflammatory cytokines (IL-10). Additionally, ICA modulated the expression of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (Gpx1) induced by LPS. The administration of ICA significantly (p < 0.05) improved the mRNA and protein expression of Toll-like receptor (TLR) 4. The western blotting and ELISA finding revealed that the ICA repressed LPS-triggered NF-κB pathway activation. Moreover, ICA improved the antioxidant defense system via activation of the Nrf2 pathway. The results revealed that ICA up-regulated the mRNA and protein expression of Nuclear erythroid-2-related factor (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) under LPS exposure. Conclusively, our findings strongly suggested that ICA protects endometritis caused by LPS by suppressing TLR4-associated NF-κB and Nrf2 pathways. Altogether, these innovative findings may pave the way for future studies into the therapeutic application of ICA to protect humans and animals against endometritis.

Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila

“…Our previous study revealed that EP supplementation inhibits Escherichia coli expansion and reduces lipopolysaccharides (LPS) in serum and colonic contents, inhibiting subsequent neuroinflammation [ 11 ]. Gluconobacter , Providencia , and Enterobacteriaceae are ubiquitous opportunistic pathogens of the Gram-negative bacteria of Drosophila [ 18 , 36 ]. In this study, we found high amounts of Gluconobacter , Providencia , and Enterobacteriaceae in aged flies ( Figure 5 C).…”

Regulatory Roles of Flavonoids in Caspase-11 Non-Canonical Inflammasome-Mediated Inflammatory Responses and Diseases

“…Icariin is a natural flavonoid found in several plant species belonging to the Epimedium genus. Icariin has biological roles and pharmacological activities, including antiaging, antiosteoporosis, antioxidative, antiatherosclerotic, and anticancer activities [ 161 , 162 , 163 , 164 , 165 ]. Additionally, icariin exerts anti-inflammatory effects by inhibiting the priming step and canonical inflammasomes in inflammatory responses and diseases [ 166 , 167 , 168 , 169 , 170 , 171 ].…”

The Role of Nursing Care in the Management of Patients with Traumatic Subarachnoid Hemorrhage

“…The inhibition of myocardial apoptosis, the prevention of inflammation on endothelial cells, the improvement of the immune system function, and the activation of HO1/ Nrf2 signaling pathways are reported as the modulatory mechanisms by which icariin exerts its therapeutical properties against cardiovascular disorders [85,86]. Furthermore, the antimicrobial function of this phytoestrogen, such as ameliorating Escherichia coli lipopolysaccharide-mediated endometritis, is suggested to be performed by inhibiting oxidative stress and inflamma GMJ.2022;11:e2809 www.gmj.ir tion [87]. In addition, the desired effects of icariin on the skeletal system, such as the alleviation of osteoarthritis and inhibition of RANKL-induced osteoclast genesis, are mediated by the regulatory role on the autophagy of chondrocytes, modification of PI3K/AKT/mTOR signaling, inhibition of reactive oxygen species (ROS) levels, and reduction in the expression of NOX1 and NOX4 [88,89].…”