Tripterygium wilfordii Glycosides Upregulate the New Anti‐Inflammatory Cytokine IL‐37 through ERK1/2 and p38 MAPK Signal Pathways

Abstract

As a Chinese traditional patent medicine, Tripterygium wilfordii glycosides (TWG) have been approved by the China State Food and Drug Administration (Z32021007) for autoimmune and inflammatory diseases. Application of TWG leads to significant decrease of the inflammatory cytokines, such as IL-6, IL-1β, and TNF-α. However, little is known whether TWG could regulate the anti-inflammatory cytokines and what the mechanism is. Here, we found that TWG could induce the upregulation of IL-37 which is a new anti-inflammatory cytokine. Furthermore, the inhibitors of ERK1/2 and/or p38 MAPK pathways suppressed IL-37 expression induced by TWG, indicating that the two pathways took part in this process. In conclusion, TWG could upregulate the anti-inflammatory cytokine IL-37 and ERK1/2 and p38 MAPK signal pathways were involved in the upregulation of IL-37 induced by TWG. The results showed that TWG had a potent activity on promoting the expression of IL-37, a new anti-inflammatory cytokine, which help further understanding the anti-inflammatory mechanism for the clinical application of TWG in therapy of diseases.

PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes

“…PG102 contains numerous compounds with anti-inflammatory properties [36]. One particular group of molecules of interest is the glycosides, as these molecules isolated from Tripterygium wilfordii Hook F have been shown to possess strong anti-inflammatory properties and upregulate IL-37 in THP-1 human macrophage cell line [37, 38]. Glycosides of various compounds are abundant in PG102 as well, so they can be obvious candidate molecules responsible for the upregulation of IL-37 [39, 40].…”

Efficacy of Tripterygium Glycosides for Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

“…Most of the studies showed that TGs can improve clinical e cacy, decrease the 24 h urinary protein, and serum creatinine. In DN, TGs not only improved proteinuria, but also alleviated kidney pathological changes and reduced the in ammation levels of kidney via p38 mapk pathway [43][44] .…”

How Does Herbal Medicine Treat Idiopathic Membranous Nephropathy?

“…Previous studies have shown that Astragalus membranaceus can regulate nuclear factor-erythroid-2-related factor 2 (Nrf2) signaling pathway, inhibit p38 MAPK, nuclear factor-kappa B (NF-κB), and toll-like receptor mediated pathway in a variety of cells ( Zhong et al., 2015 ). Tripterygium Wilfordii has also been reported to upregulate the Cytokine IL-37 through ERK1/2 and p38 MAPK Signal Pathways and decrease inflammatory by inhibiting prostaglandin E2 production ( Maekawa et al., 1999 ; Wang et al., 2017 ), Triptolide , the main active ingredient in Tripterygium glycosides, can inhibit MMP-2 and MMP-9 expression and maintains Redox Balance on rheumatoid arthritis ( Xie et al., 2019 ). Poria cocos is a well-known medicinal mushroom and it possesses various pharmacological activities such as anti-tumor, anti-inflammatory, antioxidantive, diuretic, renoprotective and lipid-lowering effects ( Wang et al., 2013 ; Chen et al., 2019d ).…”