J Ethnopharmacol: White peony total glycoside alleviates scleroderma by inhibiting type I interferon responses

Background: Interferon type I (IFN) is thought to play a causative role in systemic sclerosis (SSc, also known as scleroderma), an autoimmune rheumatic disease
.
Previous studies have found that the traditional Chinese medicine formula Si Reverse Scatter (SNS, composed of licorice, chaihu, peony and citrus aurantium) has an inhibitory effect
on the reaction of type I IFN.
Among them, peony has traditionally been used to treat inflammation-related diseases, but its therapeutic effect and potential bioactive components for type I IFN-related diseases have not been characterized
.

Objective: To identify bioactive ingredients with anti-type I IFN activity from herbal products in SNS and to further elucidate their therapeutic effects on scleroderma and their underlying mechanisms
.

Methods: A Gaussia luciferase (Gluc) reporter assay system was constructed to identify components
with anti-type I IFN activity in SNS.
In RAW264.
7 cells, real-time PCR (RT-PCR) and western blotting were used to study the induction
of the type I IFN pathway.

In addition, the expression of fibrotic genes, type I IFN-associated genes, inflammatory cytokines, and cytotoxic granules was measured by RT-PCR, and histopathological changes
were determined by H&E staining, Masson staining, and immunohistochemical analysis in the blyomycin-induced experimental scleroderma model.

Results: The data showed that white peony total glycoside (TGP), a bioactive component of SNS, selectively inhibited TLR3-mediated type I IFN response and blocked type I IFN-induced downstream JAK-STAT signaling pathway
.

In a BLM-induced mouse model of scleroderma, TGP improves skin fibrosis
by inhibiting multiple targets upstream and downstream of type I IFN signaling.
Further studies found that TGP hindered the polarization of M2 macrophages and their profibrotic effects by inhibiting Cxcl9 and Cxcl10 in the skin tissues of scleroderma mice, and reduced cytotoxic T lymphocytes and their cytotoxic granules
.

Conclusion: This study not only provides new clues for the immunomodulatory role of TGP, but also provides convincing evidence
for the development of TGP-based treatments for scleroderma and other autoimmune diseases associated with the characteristics of type I IFN.

Sources:

Li S, Bai J, Fan G, Liu R.
Total glucosides of paeony alleviates scleroderma by inhibiting type I interferon responses [published online ahead of print, 2022 Nov 2].
J Ethnopharmacol.
2022; 302(Pt A):115897.
doi:10.
1016/j.
jep.
2022.
115897