Experimental Study on Muscone Reducing NF-κB Pathway Activity by Targeting IL-1R1 to Attenuate Oxidative Stress Injury in Schwann Cells.

The underlying mechanism of how natural musk treats Bell's palsy is not clear. This study aims to reveal the potential mechanism of musk in treating peripheral nerve injury in vitro. To achieve this, an oxidative stress injury model was established in Schwann cells (SCs) using cobalt chloride (CoCl2). To assess the protective effects of Muscone (Mus) on this injury and explore its mechanism, cell viability assays, siRNA transfection, enzyme-linked immunosorbent assays (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunofluorescence staining, and ultrastructural analysis of cells were employed. As a result, it is indicated that Mus intervention enhanced SC proliferation and S-100b mRNA under hypoxia, while also reducing reactive oxygen species (ROS) and elevating superoxide dismutase (SOD) levels. Mus ameliorated oxidative stress and inflammation in hypoxic SCs by reducing IL-1β and TNF-α. Furthermore, Mus modulated key indicators involved in oxygen metabolism, cell repair, and neurometabolism, including C-JUN and GDNF. IL-1R1, localized to the SC membrane, was upregulated by hypoxia but significantly downregulated following Mus intervention. Mus also inhibited the expression of NF-κB pathway components (IRAK1, IKK, p65, p50) and increased IκB-α. Critically, abolishing IL-1R1 expression via siRNA knockdown showed a consistent effect with Mus. It is concluded that by suppressing IL-1R1, Mus attenuated inflammation in hypoxic SCs through inhibition of the NF-κB pathway. This study indicated IL-1R1's role in hypoxia-induced SC dysfunction. Furthermore, Mus might be a potentially effective medicinal for treating Bell's palsy.