Arabian Journal of Chemistry (Feb 2024)
Therapeutic effects and mechanism of action of lavender essential oil on atopic dermatitis by modulating the STAT3/RORγt pathway
Abstract
Objectives: Atopic dermatitis (AD) is a common skin disorder characterized by skin inflammation caused by an imbalance in the immune response. The efficacy of lavender essential oil in treating atopic dermatitis has been demonstrated; however, its specific mechanism of action and active components remain unknown. Therefore, this study investigated the therapeutic effects and possible mechanism of action of LEO on AD in a 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis mice model. Methods: To determine the efficacy of LEO, serum levels of the cytokines IL-6 and TNF-α were tested in Kunming mice, and network pharmacology was used to predict the targets and mechanisms of LEO in AD treatment, after which network pharmacology was combined with metabolomics to construct complex response–enzyme–gene networks and investigate their potential associations. Based on the predicted mechanisms, skin tissues were further examined by immunohistochemistry and immunoblotting analysis, and the skin epidermis was stained with hematoxylin-eosin (HE) and toluidine blue (TB). Results: LEO significantly suppressed the basal levels of IL-6 and TNF-α in the DNCB-induced mice model and predicted that Th17 cell differentiation is a critical pathway for LEO-based network pharmacology in AD treatment. As for the cytokines associated with the Th17 cell differentiation pathway, further experiments verified that LEO significantly reduced the protein expression of interleukin-17A (IL-17A)、Phosphorylated JAK2 (p-JAK)、Phosphorylated STAT3 (p-STAT3), and Retinoic acid-related orphan receptor γt (RORγt) but increased the expression of Foxp3. Additionally, the results of combined network pharmacology and metabolomics analysis showed that LEO could improve two metabolic pathways, namely, linoleic acid metabolism and arachidonic acid metabolism, by regulating the Th17 cell differentiation pathway; identify two key metabolites (linoleic acid, arachidonic acid); and regulate two differential genes (PTGS1, HPGD). Conclusion: LEO may alleviate DNCB-induced skin inflammation by inhibiting the STAT3/RORγt pathway in Th17 cell differentiation, and reducing the expression of associated inflammatory cytokines and chemokines and improving the metabolism of linoleic and arachidonic acid in vivo.
