ABSTRACT
Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1ß and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2/drug effects , Sesquiterpenes, Guaiane/therapeutic use , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Artemisia , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokines , Humans , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pandemics , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2/pathogenicity , Sesquiterpenes, Guaiane/chemistry , Sesquiterpenes, Guaiane/metabolism , Signal Transduction/drug effectsABSTRACT
Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.