Desoxo-narchinol A and water extract of Nardostachys jatamansi ameliorate house dust mite-induced atopic dermatitis by regulating Nrf2/HO-1 signaling.

Abstract

Nardostachys jatamansi has traditionally been used to treat gastrointestinal disorders. Although it was recently reported to have anti-inflammatory properties, the pharmacological potential of water extract of Nardostachys jatamansi (WENJ) against atopic dermatitis (AD)-like skin inflammation remains unclear. We investigated the effects of WENJ on a house dust mite-induced AD-like mouse model by assessing phenotypic severity, histopathological changes, and cytokine expression. Transcriptomic analysis of murine skin tissues was performed to identify gene expression signatures and key transcription factors contributing to the efficacy of WENJ. In addition, the role of the primary bioactive component of WENJ, desoxo-narchinol A, was examined in interleukin (IL)-4/IL-13-stimulated human keratinocytes, with a focus on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. In the AD-like mouse model, oral administration of WENJ markedly alleviated AD-like symptoms, reduced immune cell infiltration and inflammatory mediator expression, and restored the expression of skin barrier proteins such as filaggrin. The Nrf2/HO-1 pathway was identified as a key molecular pathway underlying the effects of WENJ on AD-like skin inflammation. Moreover, desoxo-narchinol A significantly increased Nrf2/HO-1 expression in keratinocytes, and exhibited the ability to bind Keap1 in molecular docking analysis. These findings demonstrate that WENJ and its active constituent desoxo-narchinol A exert anti-inflammatory and skin-protective effects through activation of the Nrf2/HO-1 pathway, highlighting their potential as promising therapeutic candidates for AD and related inflammatory skin conditions.