Mechanism of asiatic acid in relieving psoriasis by modulating the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.

OBJECTIVE

The purpose of this paper is to expound the effect of asiatic acid (AA) on psoriasis via modulating the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.

METHODS

An imiquimod (IMQ)-induced psoriasis model in BALB/c mice was established. Mice were divided into the control, IMQ, and AA treatment groups with different doses. Psoriasis area and severity were scored using the Psoriasis Area Severity Index (PASI). Histological changes, inflammatory factor levels in skin lesions, and expressions of NLRP3 inflammasome-related proteins and pathway proteins were measured. For cellular experiments, HaCaT cells were classified into control, model, AA low and high concentration groups, and AA-H + IGF group. Cells were stimulated with IL-17A, IL-22, TNF-α, IL-1α, and OSM (M5) to induce psoriasis-like conditions, followed by treatment with AA or IGF. Cell viability, oxidative stress levels, inflammatory factors, NLRP3 expression, and PI3K/Akt/NF-κB pathway protein levels were assessed.

RESULTS

In vivo, IMQ-induced mice showed psoriasis-like symptoms, including increased PASI scores, IL-6, TNF-α, IL-17A, and NLRP3-related protein levels. AA treatment alleviated these symptoms, reducing NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression, and restraining the PI3K/Akt/NF-κB pathway phosphorylation. In cellular experiments, M5 induction impeded cell viability and advanced oxidative stress, IL-1β, IL-6, and NLRP3 expression, activating the PI3K/Akt/NF-κB pathway. AA markedly reversed these change.

CONCLUSION

AA alleviates psoriasis symptoms by blocking the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.