Ginsenoside Rg3 Ameliorates Psoriasis-Like Dermatitis through Inhibition of NF-κB/NLRP3 Inflammasome Signaling and Regulating Th17/Treg Balance.

BACKGROUND

Psoriasis, characterized as a persistent cutaneous inflammatory condition driven by aberrant immunity, exhibits pathogenesis and disease course heavily influenced by sustained inflammatory activity. Ginsenoside Rg3 (Grg3), a traditional Chinese medicinal compound, has shown notable therapeutic effects on various inflammatory diseases. However, its therapeutic efficacy and mechanisms of action in the treatment of psoriasis remain unclear.

METHOD: In this study, we utilized 6 to 8-week-old female BALB/c mice and applied 5% imiquimod (IMQ) cream to their dorsal skin to establish a psoriasis-like dermatitis model. Twenty-five mice were randomly divided into five groups: control, model, and the Grg3-L/M/H groups, receiving dosages of 5, 10, and 20 mg/kg/day, respectively, with three mice in each group. Grg3 was administered continuously for 7 days to evaluate its effects on the skin of the psoriasis mice. The following methodologies were employed: the Psoriasis Area and Severity Index) for clinical severity scoring, hematoxylin-eosin staining for histomorphological analysis, alongside immunohistochemistry, immunofluorescence, and flow cytometry for detailed protein and cellular profiling to assess the expression levels of the keratinocyte proliferation marker Ki-67, inflammatory cytokines, NLRP3 inflammasome-related factors, and NF-κB pathway-related proteins in vivo.

RESULT: Significant reductions in PASI scores were observed in IMQ-treated BALB/c murine models of psoriasis following Grg3 treatment. It decreases epidermal thickness, inhibits the proliferation and differentiation of epidermal cells, and reduces the expression of the inflammatory cytokine interleukin-17 (IL-17) in splenic lymphocytes. Additionally, an increase in Foxp3 + CD4+ regulatory T cell (Treg) proportion and a decrease in the expression levels of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, and IL-1β were observed following Grg3 administration. Furthermore, A concomitant downregulation of p-p65 expression and its downstream effectors, such as the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), was also observed.

CONCLUSION

Our findings indicate that Grg3 confers protective effects in a murine model of imiquimod-induced psoriasis-like dermatitis. The potential therapeutic properties of Grg3 potentially involve modulation of NLRP3 inflammasome activation, suppression of NF-κB signaling, and restoration of Th17/Treg cell homeostasis.