The potential of hydroxysafflor yellow a as an adjuvant in covid-19 patients with acute respiratory distress syndrome

Objective: To discuss the potential and molecular mechanism of Carthamus tincorius derived hydroxysafflor yellow A (HSYA) as an alternative herbal adjuvant that may regulate various signaling pathways that might be related to the regulatory effects in COVID-19 patients with ALI and ARDS. Methods: We search Web of Science, PubMed, and Scopus using keywords: Carthamus tinctorius, adjuvant, cytokine storm, COVID-19, SARS-Cov-2, acute lung injury (ALI), and Acute Respiratory Distress Syndrome (ARDS), on 11 September 2020, and 18 December 2020. Results and Discussions: In COVID-19 patients, SARS-CoV-2 replication might be associated with hyper induction of pro-in-flammatory cytokine, which is known as a cytokine storm, and may cause acute lung injury (ALI) that leads to Acute Respiratory Distress Syndrome (ARDS). Carthamus tincorius derived HSYA were used in many studies, in vivo in animal models or in vitro in cell lines and showed inhibition of multiple inflammatory pathways that were involved in ALI and ARDS, which might occur in covid-19 patients. HSYA showed pleiotropic effects in regulating cytokine levels. It regulated TNF-α, IL-1β, IL-6, IFN-β, and showed protective effect by blocking TLR4, MyD88, TRIF, IRF3, NF-κB to avoid cytokine storm and prevent tissue damage. HSYA was showed to reduce oxidative stress-mediated damage, and down-regulate inflammatory cytokines. Further, it was relatively safe when studied as an adjuvant in HIV and cancer patients. Conclusion: We supposed that HSYA could be used as an alternative adjuvant in COVID-19 patients with ARDS. However, clinical trials are needed to prove its efficacy in COVID-19 patients with ARDS.