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

TL;DR

Ginsenoside Rg3 reduces psoriasis-like skin inflammation in mice by suppressing harmful immune signals and restoring immune balance.

Contribution

This study reveals a novel therapeutic mechanism of Ginsenoside Rg3 in psoriasis through inhibition of NLRP3 inflammasome and NF-κB signaling.

Findings

Ginsenoside Rg3 significantly reduced PASI scores and epidermal thickness in psoriasis-like dermatitis models.

Grg3 suppressed IL-17 and pro-inflammatory cytokines while increasing regulatory T cells in psoriasis mice.

The compound inhibited NLRP3 inflammasome activation and NF-κB signaling pathways in vivo.

Abstract

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.

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.

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.

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.

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