<b><i>Introduction:</i></b> As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. <b><i>Methods:</i></b> The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD’s effective components. <b><i>Results:</i></b> The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. <b><i>Conclusions:</i></b> In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. Appropriate treatment of allergic rhinitis should be explored thoroughly. In recent years, more attention has been paid to the advantages of traditional Chinese medicine in the treatment of AR. Xiaoqinglong decoction (XQLD) as a classical Chinese medicine prescription has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more therapeutic mechanisms remain to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. Liquid chromatography–mass spectrometry (LC–MS) was adopted to test the stability of XQLD’s effective components. The research was evaluated in an ovalbumin sensitized AR mouse model. The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3 and HDAC4) and Th2 inflammatory factors (IL4, IL5 and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (Claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. In conclusion, our findings confirm that XQLD may be responsible for the recovery of nasal epithelial dysfunction and inhibiting Th2 inflammation in AR by downregulating HDAC expression and HDAC is a crucial and promising target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.