Sesquiterpenes from galangal essential oil as potent penetration enhancer: Effect on stratum corneum components and cutaneous TRPV4 ion channel

Natural terpenes found in essential oils (EOs) have shown promise as penetration enhancers (PEs) in pharmaceutical and cosmetic formulations. This study compared the skin penetration enhancement properties of sesquiterpenes and monoterpenes from galangal EO (GEO), e.g. δ-cadinene, β-caryophyllene, caryophyllene oxide (CPO), 4-terpineol, β-pinene, and 1,8-cineole. Results indicated that the sesquiterpenes, particularly δ-cadinene, significantly improved the skin permeation of rhodamine B compared to monoterpenes. Electrical resistance measurements of the skin, DSC and XRD analysis revealed that the sesquiterpenes notably disturbed the ordered arrangement of stratum corneum (SC) components including lipids and keratins. Additionally, the results of molecular docking also revealed that sesquiterpenes were easily combined with transient receptor potential vanilloid 4 (TRPV4) ion channel. The cutaneous TRPV4 ion channel, which played a role in tight junction (TJ) formation in keratinocytes, were abundantly expressed in rat abdominal skin. δ-Cadinene, specifically, exhibited an agonistic effect on the cutaneous TRPV4 ion channel, significantly enhancing its SC retention and facilitating in vivo skin permeation of rhodamine B. In summary, the penetration enhancement mechanism of sesquiterpenes from GEO, particularly δ-cadinene, includes acting on SC components and activating the cutaneous TRPV4 ion channel.