Summary
The
outbreak of SARS warrants the search for antiviral compounds to treat
the disease. At present, no specific treatment has been identified for
SARS-associated coronavirus infection. We assessed the antiviral
potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid,
and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and
FFM-2) from patients with SARS admitted to the clinical centre of
Frankfurt University, Germany. Of all the compounds, glycyrrhizin was
the most active in inhibiting replication of the SARS-associated virus.
Our findings suggest that glycyrrhizin should be assessed for treatment
of SARS.
https://www.ncbi.nlm.nih.gov/pubmed/30634142/
Int Immunopharmacol. 2019 Mar;68:145-155. doi: 10.1016/j.intimp.2019.01.002. Epub 2019 Jan 8.
Glycyrrhizin attenuates hepatic ischemia-reperfusion injury by suppressing HMGB1-dependent GSDMD-mediated kupffer cells pyroptosis.
Abstract
Gasdermin D (GSDMD), a genetic substrate for inflammatory caspases, plays a central role in pyroptosis of macrophages and release of interleukin‑1β (IL-1β), but was mainly referred to microbial infection. High mobility group box-1 (HMGB1), served as an alarm molecule during various pathological process, has been widely recognized to be involved in liver ischemia-reperfusion (I/R). Glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, was recently referred to have ability to prevent I/R induced liver injury by inhibiting HMGB1 expression and activity. However, the mechanisms responsible for damage amelioration subsequently to HMGB1 inhibition during liver I/R remain enigmatic. This study was designed to explore the functional role and molecular mechanism of glycyrrhizin in the regulation of I/R induced liver injury. We found that liver I/R promotes GSDMD-mediated pyroptotic cell death of Kupffer cells, which was inhibited by glycyrrhizin. Interestingly, endogenous HMGB1, not exogenous one, was involved in hypoxia-reoxygenation (H/R) induced pyroptosis. Moreover, GSDMD knockdown protects kupffer cells against H/R induced pyroptosis in vitro. Here, we report, for the first time, that glycyrrhizin attenuated tissue damage and kupffer cells pyroptosis during liver ischemia-reperfusion injury (LIRI) and identify a previously unrecognized HMGB1- dependent GSDMD- mediated signaling pathway in the mechanism of kupffer cells pyroptosis induced by H/R. Our findings provide the first demonstration of GSDMD-determined pyroptotic cell death responsible for I/R induced release of IL-1β and this would provide a mandate to better understand the unconventional mechanisms of cytokine release in the sterile innate immune system.Mitä on glykyrriziini? Lakritsijauheen sisältämä molekyyli
https://fi.wikipedia.org/wiki/Lakritsihappo
