Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

Abstract

Enterovirus 71 (EV71) is one of the primary pathogens involved in severe hand, foot and mouth disease in children. EV71 infection causes various types of programmed cell death. However, there are currently no clinically approved specific antiviral drugs for control of EV71 infection. Astragalus membranaceus (AM), a Traditional Chinese medicine, has been used in antiviral therapy in China. The aim of the present study was to determine whether total astragalosides (ASTs), bioactive components of AM, protect against EV. DAPI nuclear staining was used to observe morphological changes of the nucleus and the protective effect of ASTs, which revealed that the nucleus shrank following EV71 infection, while ASTs reversed it. Cell Counting Kit-8 assay found that human normal gastric epithelial cell (GES-1 cell) viability decreased following EV71 infection, while lactate dehydrogenase (LDH) assay showed that EV71 infection induced GES-1 cell damage. Western blotting was used to measure the expression levels of apoptosis and pyroptosis marker protein to determine whether EV71 infection induced apoptosis and pyroptosis in GES-1 cells. Reverse transcription-quantitative PCR was used to determine the anti-EV71 effect of ASTs. The results showed that ASTs protected GES-1 cells from EV71-induced cell apoptosis and pyroptosis. Furthermore, the present data demonstrated that the protective effect of ASTs was exerted by suppressing EV71 replication and release. These findings suggested that ASTs may represent a potential antiviral agent for the treatment of EV71 infection.

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF‐κB/NLRP3 axis

“…Moreover, astragalus membranaceus is reported to suppress EV71 replication and protect cells against EV71-induced apoptosis and pyroptosis. [49] Caspase-1 inhibitor suppressed the EV71 replication, IL-1β and IL-18 secretion, and improved the host response during EV71…”

“…Moreover, astragalus membranaceus is reported to suppress EV71 replication and protect cells against EV71‐induced apoptosis and pyroptosis. [ 49 ] Caspase‐1 inhibitor suppressed the EV71 replication, IL‐1β and IL‐18 secretion, and improved the host response during EV71 infection. [ 50 ] Similarly, the inhibition of HMGB1 inhibited the activation of NLRP3 inflammasome and pyroptosis in EV71‐infected cells.…”

Role of the NLRP3/caspase-1/GSDMD signaling pathway in dopaminergic neurons during Japanese encephalitis virus infection

“…It is a form of death characterized by the appearance of pores in the cell membrane, resulting in changes in the osmotic pressure inside and outside the cell, followed by cell swelling [17,18]. Many infectious diseases point to the necessity of gasdermin family proteins (mainly GSDMD) in pyroptosis [19][20][21]. A related study in a mouse model of JEV infection showed that GSDMD was signi cantly elevated at the transcriptional level, indicating that pyroptosis was involved in viral infection during the period of pronounced clinical symptoms [22].…”

The neuropathological mechanism of EV-A71 infection attributes to inflammatory pryoptosis and viral replication via activating the hsa_circ_0045431/ hsa_miR_584/NLRP3 regulatory axis

“…Actually, growing evidence has been clearly pointed out that pyroptosis exerted an important role in EV-A71 infection ( Wang et al., 2022b ). For instance, EV-A71 infection induced gastric epithelial cells damage by triggering pyroptosis ( Zhang et al., 2022 ). AIM2 inflammasome-mediated pyroptosis in EV-A71-infected neuronal cells restricts viral replication.…”