Psoriasis and Oridonin

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These findings provide a valuable experimental and mechanistic basis to understand the pharmacological actions of oridonin and lay the groundwork for further investigations into its potential application for psoriasis.

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Objective:
Oridonin is a key bioactive compound extracted from Rabdosia rubescens. This study aims to explore the potential role and underlying mechanisms of oridonin against psoriasis-like injury, both in vivo and in vitro.

Methods:
Transcriptomics was used to profile risk genes in psoriasis-like mice. Both Masson’s trichrome staining and hematoxylin & eosin staining were performed to examine the skin histopathology. The viability, apoptosis, cell cycle progression, invasion, and migration of HaCaT keratinocytes were assessed concurrently. Furthermore, the expression levels of eukaryotic elongation factor-2 kinase (eEF2K), p-STAT3, STAT3, and secreted phosphoprotein 1 (SPP1) were determined both in vivo and in vitro.

Results:
Oridonin remarkably inhibited the eEF2K/p-STAT3/SPP1 pathway both in vivo and in vitro. Silencing of eEF2K or the administration of oridonin significantly diminished the thickening of both the epidermal and spinous layers, while concurrently inhibiting inflammatory infiltration and collagen fiber accumulation in skin lesions observed in a psoriasis-like mouse model. Meanwhile, the secretion of inflammatory cytokines and the excessive proliferation, migration, and invasion of M5-induced HaCaT keratinocytes were partially attenuated following oridonin treatment or eEF2K silencing. In contrast, overexpression of eEF2K counteracted the protective effect of oridonin on psoriasis both in vivo and in vitro.

Conclusions:
Oridonin is a promising compound that demonstrates protective effects in psoriasis by inhibiting keratinocyte hyperproliferation and inflammation. This biological activity is mediated through inhibition of the eEF2K/p-STAT3/SPP1 pathway. These findings provide valuable mechanistic insights for understanding the pharmacological property of oridonin and support further investigation for its potential clinical application.

Source: onlinelibrary.wiley.com

*Funding: National Natural Science Foundation of China. | Norman Bethune Public Welfare Fund.