Objective

2

To explore the therapeutic mechanism of Wumei Wan on a rat model of allergic rhinitis （AR） with the pattern of cold-heat complex based on its regulatory effects on interleukin （IL）-10， IL-17 cytokines and tight junction proteins including zonula occludens-1 （ZO-1） and Occludin.

Methods

2

Sixteen rats were randomly selected from 108 Wistar rats as the control group. The remaining rats were used to establish a cold-heat complex pattern AR model via alternating intragastric administration of propylthiouracil and the decoction of Anemarrhenae Rhizoma and Gypsum Fibrosum， combined with ovalbumin sensitization. After successful modeling， the remaining successfully modeled rats were randomly divided into the model group （

n

=14）， loratadine group （1.2 mg/kg，

n

=14）， and high- （2.0 g/kg，

n

=16）， medium- （1.0 g/kg，

n

=14）， and low- （0.5 g/kg，

n

=14） dose Wumei Wan groups. The control group and model group were administered 0.9% sodium chloride solution via intragastric administration， while the other groups received their respective treatments once daily for 6 consecutive weeks. After treatment， rat behavioral scores were recorded. Serum levels of IL-10 and IL-17 were detected by enzyme-linked immunosorbent assay （ELISA）， and the protein expressions of ZO-1 and Occludin in intestinal tissues and nasal mucosa tissues were determined by Western blot. Dose-effect analysis was conducted to clarify the differences in effects among different doses of Wumei Wan and to identify the optimal effective dose.

Results

2

Behavioral score of the model group was significantly higher than that in the blank control group （

P

<

0.01）； the scores of all Wumei Wan groups and the loratadine group were all significantly lower than that of the model group （

P

<

0.01）. Compared with the blank control group， the serum IL-10 level of the model group decreased markedly and the IL-17 level increased markedly （

P

<

0.001）. After intervention with high-， medium- and low-doses of Wumei Wan and loratadine， the serum IL-10 levels of all treatment groups were obviously higher than that of model group （

P

<

0.01，

P

<

0.001） and serum IL-17 in the medium-， high-dose groups of Wumei Wan and the loratadine group were significantly lower than that of the model group （

P

<

0.001）. Additionally， the protein expressions of ZO-1 and Occludin in intestinal and nasal mucosa tissues of medium-， high-dose Wumei Wan groups and loratadine group were obviously higher than those of the model group （

P

<

0.05，

P

<

0.01）. The dose-effect analysis results showed that as the dosage of Wumei Wan increased， the behavioral score of rats gradually decreased while the serum IL-10 level and the expression of ZO-1 and Occludin proteins in intestinal tissue and nasal mucosa tissues gradually increased， and the serum IL-17 level gradually decreased. Among them， the high-dose group had the best effect （

P

<

0.05）.

Conclusion

2

Wumei Wan can improve the symptoms of cold-heat complex pattern AR in rats. Its therapeutic mechanism is related to downregulating serum IL-17， upregulating serum IL-10， and enhancing the protein expressions of ZO-1 and Occludin in intestinal tissues.