Anti-Psoriatic Effect of Rheum palmatum L. and Its Underlying Molecular Mechanisms

Psoriasis is a chronic, immune-mediated inflammatory skin disorder. Rheum palmatum L. is a common traditional medicinal herb with anti-inflammatory and immunomodulatory activities. This study aimed to investigate the anti-psoriatic effects of the ethanolic extract from R. palmatum L. (RPE) and its chemical constituents, as well as the mechanisms underlying their therapeutic significance. An imiquimod (IMQ)-induced psoriasis-like mouse model was used to examine the anti-psoriatic effect of RPE in vivo. Network pharmacological analysis was performed to investigate the potential targets and related pathways of the RPE components, including rhein, emodin, chrysophanol, aloe-emodin, and physcion. The anti-inflammatory effects and underlying mechanisms of these components were examined using in vitro models. Topical application of RPE alleviated psoriasis-like symptoms and reduced levels of inflammatory cytokines and proliferation markers in the skin. Network pharmacological analysis revealed that RPE components target 20 genes that are linked to psoriasis-related pathways, such as IL-17, MAPK, and TNF signaling pathways. Among the five components of RPE, rhein and emodin showed inhibitory effects on TNF-α and IL-17 production in EL-4 cells, attenuated the production of CXCL8, CXCL10, CCL20, and MMP9, and reduced proliferation in HaCaT cells. Chrysophanol, aloe-emodin, and physcion were less effective than rhein and emodin in suppressing inflammatory responses and keratinocyte proliferation. The effects of these compounds might occur through the inhibition of the ERK, STAT3, and NF-κB signaling pathways. This study suggested the anti-psoriatic effect of RPE, with rhein and emodin as the main contributors that regulate multiple signaling pathways.