Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways

Abstract

The duck virus hepatitis (DVH) caused by the duck hepatitis virus A (DHAV) has produced extensive economic losses to the duck industry. The currently licensed commercial vaccine has shown some defects and does not completely prevent the DVH. Accordingly, a new alternative treatment for this disease is urgently needed. Previous studies have shown that icariin (ICA) and its phosphorylated derivative (pICA) possessed good anti-DHAV effects through direct and indirect antiviral pathways, such as antioxidative stress. But the antioxidant activity showed some differences between ICA and pICA. The aim of this study is to prove that ICA and pICA attenuate oxidative stress caused by DHAV in vitro and in vivo, and to investigate their mechanism of action to explain their differences in antioxidant activities. In vivo, the dynamic deaths, oxidative evaluation indexes and hepatic pathological change scores were detected. When was added the hinokitiol which showed the pro-oxidative effect as an intervention method, pICA still possessed more treatment effect than ICA. The strong correlation between mortality and oxidative stress proves that ICA and pICA alleviate oxidative stress caused by DHAV. This was also demonstrated by the addition of hydrogen peroxide (H2O2) as an intervention method in vitro. pICA can be more effective than ICA to improve duck embryonic hepatocytes (DEHs) viability and reduce the virulence of DHAV. The strong correlation between TCID50 and oxidative stress demonstrates that ICA and pICA can achieve anti-DHAV effects by inhibiting oxidative stress. In addition, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of ICA and pICA showed significant difference. pICA could significantly inhibit the phosphorylation of p38, extra cellular signal regulated Kinase (ERK 1/2) and c-Jun N-terminal kinase (JNK), which were related to mitogen-activated protein kinases (MAPKs) signaling pathways. Ultimately, compared to ICA, pICA exhibited more antioxidant activity that could regulate oxidative stress-related indicators, and inhibited the phosphorylation of MAPKs signaling pathway.

The protective effect of icariin and phosphorylated icariin against LPS-induced intestinal goblet cell dysfunction

“…At present, the exact mechanism underlying the effects of ICA and pICA is not fully understood, but it may be related to the antioxidant properties of ICA and pICA. 24 Regarding antioxidant activity, data from current studies showed that ICA and pICA significantly reduce mitochondrial ROS, intracellular ROS, and intracellular MDA and H 2 O 2 levels in LS174T cells. Meanwhile, the enzyme activities of SOD, GPx, CAT, and T-AOC after ICA and pICA treatment were also significantly increased.…”

“…22,23 In our previous study, phosphorylated ICA (pICA) was obtained by altering the covalent modification of ICA, and we found that pICA is not only more soluble in water than ICA, but also has stronger antioxidant, anti-inflammatory, and anti-duck hepatitis virus effects. 24,25 However, whether ICA and pICA can antagonize LPS-induced changes in intestinal goblet cell function remains unclear. Therefore, in the present study, human intestinal goblet LS174T cells were used as a model to study the effects of LPS on the function of intestinal goblet cells.…”

Icariin and its phosphorylated derivatives alleviate intestinal epithelial barrier disruption caused by enterotoxigenic Escherichia coli through modulate p38 MAPK in vivo and in vitro

“…17,18 There was study found that phosphorylated p38 MAPK protein level dramatically elevates in ETEC-induced weaned pig diarrhea, suggesting that p38 MAPK has an important contribution to ETEC-induced diarrhea. 20 Therefore, we hypothesize that ICA and pICA have protective effects on the intestinal epithelial barrier function of ETEC-induced piglet diarrhea by regulating the expression of p38 MAPK. 20 Therefore, we hypothesize that ICA and pICA have protective effects on the intestinal epithelial barrier function of ETEC-induced piglet diarrhea by regulating the expression of p38 MAPK.…”

The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats

“…Bioactive compounds, including proanthocyanidins and icariin, in some food show anti-resorptive and anti-inflammatory properties, high antioxidant capacity and phytoestrogenic activity [ 8 , 9 , 10 ]. Phytoestrogens can attenuate bone loss associated with oestrogen deficiency by acting similarly to oestrogen, as well as through antioxidative properties and their influence on antioxidant enzyme activity in both animal and human studies [ 11 ].…”

“…Since proanthocyanidins and icariin are powerful antioxidants and phytoestrogens [ 8 , 9 , 10 ] they may be useful in the treatment of osteoporosis induced by retinoic acid. In present study we have investigated the therapeutic effect of proanthocyanidins and icariin on 13 cis-retinoic acid (13cRA) induced osteoporosis in rats as a drug-induced bone loss model.…”