Pomegranate Peel Extract Alleviates Psoriasis-like Skin Lesions in Mice Through the Suppression of AhR-Activating Th17/IL-17 Axis and Neuronal-Related Pathways

Psoriasis is a refractory skin disease that is often accompanied by systemic comorbidities. While the efficacy of biologics in treating psoriasis is well-established, these treatments are also associated with frequent adverse reactions. Consequently, there is an urgent need to develop new treatment strategies for psoriasis. Pomegranate peel, which is widely used in skincare and protection, has not been fully studied for its therapeutic potential in psoriasis. This article investigates the therapeutic effectiveness of pomegranate peel ethanol extract (PEE) on psoriasis. A total of 2872 compounds were identified in PEE. The topical application of PEE alleviated primary psoriasis-like skin lesions and reduced lesion recurrence in mice. PEE simultaneously activates AhR and inhibits the Th17/IL-17 axis and neuronal-related pathways, which may serve as a mechanism for PEE in the treatment of psoriasis. In conclusion, our study establishes that PEE may serve as a novel therapeutic agent for psoriasis, with a unique mechanism of action that simultaneously activates AhR and suppresses neuronal-related pathways.