Yujie Li,1 Yadong Yin,2 Juan Xiong,3 Zhipeng Zhang,4 Linglong Li,3 Baoshun Zhang,4 Feng Zhang,3 Dehong Mao3 

1College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Xijing Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 3Department of Otorhinolaryngology, Yongchuan Chinese Medicine Hospital Affiliated to Chongqing Medical University, Chongqing, People’s Republic of China; 4College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China

Correspondence: Feng Zhang; Dehong Mao, Email 164382044@163.com; 19m001@hospital.cqmu.edu.cn

Background: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear.
Purpose: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments.
Methods: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation.
Results: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro.
Conclusion: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

Keywords: Yujiang paidu decoction, chronic rhinosinusitis with nasal polyps, network pharmacology, transcriptomics, inflammation