Shufeng Jiedu capsule ameliorates olfactory dysfunction via the AMPK/mTOR autophagy pathway in a mouse model of allergic rhinitis

Abstract

Background: Shufeng Jiedu capsule (SFJDC) has been widely used as a conventional Chinese pharmaceutical agent for various upper respiratory infections, including acute lung injury, acute respiratory distress syndrome and allergic rhinitis (AR). However, its mechanism in AR remains unclear.

Purpose: The present study aimed to decipher the antiallergic inflammatory effect of SFJDC in an AR model with olfactory dysfunction. Specifically, we wanted to explore whether SFJDC can improve the olfactory abnormality in AR mice and reduce the levels of inflammatory factors in the olfactory epithelium (OE) and olfactory bulb (OB).

Methods: To address the above issues, we constructed an AR model using C57BL/6 mice, which were sensitised and challenged with ovalbumin (OVA) by intraperitoneal injection. SFJDC (0.045 or 0.18 g/kg) was delivered by gavage administration 1 h prior to the intraperitoneal injection of OVA. The control mice received saline alone. Then, the animals were assessed according to the presence of nasal symptoms and nasal inflammation, and a buried food test was used to evaluate olfactory function. The levels of proteins involved in the AMPK/mTOR autophagy pathway in the OE and OB were investigated by western blotting and fluorescence staining.

Results: After OVA induction of AR and drug administration, we found that SFJDC significantly ameliorated the nasal symptoms and allergic inflammatory reaction of the nasal mucosa superior to cetirizine. A behavioural test indicated that the mice with AR had olfactory dysfunction, and SFJDC can ameliorate this behavior deficiency. Meanwhile, SFJDC clearly reduced the neuroinflammation level in OE tissue. In addition, SFJDC increased p-mTOR and decreased p-AMPK, beclin1, LC3 and cleaved caspase-3 levels in the OE.

Conclusions: In addition to antibacterial and antiviral activities, SFJDC has marked anti-inflammatory effects in AR mice. Its mechanism of action in the nasal cavity involves inhibition of upregulated anti-inflammatory cytokines, modulation of autophagy and apoptosis levels and regulation of autophagy through the AMPK/mTOR pathway in the OE tissue of AR mice. Hence, SFJDC is a promising drug for AR, and clinical trials should further validate the therapeutic impact of SFJDC on AR with olfactory dysfunction.

Keywords: AMPK; Allergic rhinitis; Autophagy; Olfactory dysfunction; SFJDC; mTOR.