Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein

Abstract

Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV) infection, leads to significant economic losses in the swine industry worldwide. In our studies, we found that glycyrrhizin, the major component of licorice root extracts, could moderately inhibit PEDV infection in Vero cells, when analyzed by western blot, qRT-PCR and a plaque formation assay. We also revealed that glycyrrhizin inhibited the entry and replication of PEDV. In addition, we demonstrated that glycyrrhizin decreased the mRNA levels of proinflammatory cytokines. Since glycyrrhizin is a competitive inhibitor of high mobility group box-1 (HMGB1), we confirmed that TLR4 and RAGE (£ associated with PEDV pathogenesis during the infection in Vero cells. In summary, our studies provide a molecular basis for developing novel therapeutic methods to control PEDV infection, based on glycyrrhizin and its derivatives.

Glycyrrhizin Inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 Pathway

“…The MAPK p38 pathway is a key regulator of inflammatory responses [33][34][35][36]. HMGB1 binding to TLR4 triggers cytokine release under the prerequisite of both a disulfide bond between C23 and C45 and a reduced C106 of HMGB1 [46], and our previous study corroborates the fact that extracellular HMGB1 binding to TLR4 promotes inflammatory responses [26]. Therefore, we speculated that TLR4 might regulate PEDV infection and that inflammatory responses depended on activation of signaling cascades.…”

“…GLY is a competitive inhibitor of HMGB1 cytokine activity. Our previous study demonstrated that GLY could block of binding HMGB1 to TLR4 and impair the activity of TLR4 [26]. Our results showed that GLY decreased the activity of p38 dependent on TLR4 activation.…”

“…HMGB1 is a unique mediator of inflammation-associated events and innate immune responses [25]. We previously showed that GLY inhibited PEDV [26], but the anti-PEDV mechanisms of GLY remain unclear.…”

Quantitative Proteomic Analysis Reveals Antiviral and Anti-inflammatory Effects of Puerarin in Piglets Infected With Porcine Epidemic Diarrhea Virus

“…Inflammation and disease progression are initiated by proinflammatory cytokines and chemokines during viral infection (51). A previous study showed that the mRNA levels for pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-8, and TNFα) were increased in Vero cells after PEDV infection (52). MCP1/CCL2, which is a chemokine, was also increased in response to PEDV infection (53).…”

Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review

“…Glycyrrhizin can also be used as a novel therapeutic method to control porcine epidemic diarrhoea virus (PEDV) infection, inhibiting the infection of Vero cells (namely, the entry and replication of PEDV) and decreasing the mRNA levels of proinflammatory cytokines (Huan et al, ).…”