Study on the percutaneous absorption and synergistic anti-rheumatoid arthritis effect of the Zanthoxylum bungeanum essential oil on Qin Jiao-Du Huo.

Rheumatoid arthritis (RA) is an autoimmune disorder marked by chronic synovitis and systemic complications. The Gentiana macrophylla-Angelica pubescens (Qinjiao-Duhuo, Q-D) pair offers anti-RA potential but suffers from low oral bioavailability. Transdermal delivery bypasses gastrointestinal irritation and first-pass effects, but stratum corneum barriers limit permeability. Natural penetration enhancers, Zanthoxylum bungeanum essential oil (ZBEO) enhances drug penetration and alleviates inflammation in RA models, suggesting synergistic benefits with Q-D extracts. However, the mechanism is not fully understood. The purpose of this study was to investigate the transdermal permeation mechanism of ZBEO on Q-D and its synergistic anti-RA effect. A total of 533 compounds were analyzed from UPLC-Q-Exactive Orbitrap MS of Q-D. Seven core components of Q-D for the therapy of RA were identified, and the PI3K-AKT signaling pathway was identified as the primary action pathway. As demonstrated by ATR-FTIR and other techniques, ZBEO increased the cumulative transmission of key components of Q-D. This was achieved by disrupting the lipid arrangement of the skin stratum corneum, among other processes. The cellular assay demonstrated that ZBEO-Q-D significantly inhibited the proliferation of MH7A cells and lowered the levels of inflammatory factors. In vivo investigations revealed that ZBEO-Q-D significantly alleviated the symptoms of RA rats. In this study, ZBEO enhanced the transdermal penetration efficiency of the key components of Q-D by enhancing the lipid mobility of the stratum corneum and enlarging the cell gap and alleviated the synovial inflammation of RA, which provided a new strategy for the treatment of RA with Chinese herbal medicine administered transdermally.