Effects of Korean Red ginseng on the regulation of inflammation, cell death, and fibrosis in a mouse model of rheumatoid arthritis featuring spike protein overexpression.

COVID-19 causes inflammation, autoantibody production, and thrombosis-features commonly observed in autoimmune diseases like rheumatoid arthritis (RA). In RA patients infected with COVID-19, immunosuppressive treatments can weaken viral defenses and worsen inflammation. The effects of red ginseng on these patients remain unexplored. We investigated the therapeutic potential of red ginseng extract (RGE) in an RA model with SARS-CoV-2 spike protein overexpression. Plasmids expressing the SARS-CoV-2 spike protein and ACE2 were delivered into mice with collagen-induced arthritis (CIA). They were orally administered RGE, and effects were assessed via immunohistochemistry, confocal analysis, and ELISA. We analyzed the regulation of Th17 and Treg cells and related cytokines, as well as markers of inflammation, cell death, and fibrosis in splenocytes and fibroblasts. We also examined the combined effects of RGE and methotrexate (MTX). Oral RGE supplementation improved joint inflammation and damage, increasing Treg cells in the spleen. RGE reduced the expression of inflammatory cytokines (IL-17, IL-6, MCP-1, IL-1β, TNF-α), cell death markers (pMLKL, Caspase1), and fibrosis markers (α-SMA, Col1A1) in synovial tissue. In vitro, RGE decreased the expression of these markers in fibroblasts and splenocytes. RGE and MTX had inhibitory effects in the CIA model, with regulatory effects on immune cells, suppressing Th17 cells and enhancing Treg cells. RGE inhibits inflammatory cell death, fibrosis, and modulates immune cells. Its inhibitory effect with MTX suggests therapeutic benefits for RA patients co-infected with COVID-19.