6-Shogaol Exhibits Anti-viral and Anti-inflammatory Activity in COVID-19-Associated Inflammation by Regulating NLRP3 Inflammasomes

Abstract

Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO displayed mechanistic action by regulating the expression of the inflammasome pathway molecules. In comparison to the existing drugs, remdesivir and hydroxy-chloroquine, 6-SHO was not only found to be as effective as the standard anti-viral drugs but also much superior and safe in terms of predicted physicochemical properties and clinical toxicity. Comparative molecular dynamics simulation demonstrated a stable interaction of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit water environment. Overall, this study provides important cues for further development of 6-SHO as potential anti-inflammatory and anti-viral therapeutic agents.

An overview of 6-shogaol: new insights into its pharmacological properties and potential therapeutic activities

“…In a study, 6-shogaol showed an inhibitory effect on the growth of SARS-CoV2. 36 In addition, patients with COVID-19 symptoms showed severe inflammation, including the levels of several pro-inflammatory cytokines, including IL-6. 6-Shogaol inhibited the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and reduced the expression of inflammatory factors, and is a potential anti-inflammatory and anti-COVID-19 drug.…”

“…6-Shogaol inhibited the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and reduced the expression of inflammatory factors, and is a potential anti-inflammatory and anti-COVID-19 drug. 36…”

“…6-Shogaol inhibited the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and reduced the expression of inflammatory factors, and is a potential antiinflammatory and anti-COVID-19 drug. 36 An intricate immune system response, such as inflammation, defends organs against infection and tissue damage. The host benefits from a regulated inflammatory response because it removes immune stimulants from host tissues, and restores structural and physiological functions.…”

Review of the anticancer properties of 6‐shogaol: Mechanisms of action in cancer cells and future research opportunities

“…It efficiently regulates processes like inflammation, production of ROS (Zhao et al, 2020), and secretion and rifting of proinflammatory cytokines by the caspase-1 pathway, as well as virus infection management (Wofford et al, 2020). In this regard, Kode et al (2023) assessed the antiviral and anti-inflammatory properties of 6-shogaol during a SARS-CoV2 infection and its role in the NLRP3 inflammasome route in various cell lines. For Vero cells, 6-shogaol demonstrated a successful inhibition of the viral infection in a dose-dependent manner, with an EC50 of 0.95 μg/mL; meanwhile, the positive control compound, remdesivir, exhibited an EC50 of 0.90 μg/mL (Pruijssers et al, 2020).…”

“…This tool is vital in studying new drugs or their repositioning (Luo et al, 2016). Kode et al (2023) established that 6-shogaol interacts with the NLRP3 inflammasome, specifically in the ADP-binding cavity, thus inhibiting the protein complex activity related to the proinflammatory cascades (Zhao et al, 2021). It was also shown that 6-shogaol interacts with the cavity predominantly by hydrophobic bonds and with H-bonds to a lesser extent.…”