Jieyu Guben decoction alleviates combined allergic rhinitis and asthma syndrome by balancing Th17/Treg expression and restoring PPARD

BACKGROUND: This study was designed to assess the efficacy of the Jieyu Guben Decoction (JYGBD), a novel formula that has not been reported, in treating rats with combined allergic rhinitis and asthma syndrome (CARAS) and the mechanism. METHODS: CARAS rats were induced by ovalbumin (OVA) sensitization and treated with JYGBD to analyze the allergic symptoms and the production of OVA-specific antibodies. Hematoxylin-eosin staining, periodic acid-Schiff staining, Toluidine blue staining, Giemsa staining, and MASSON staining were applied to examine the impact of JYGBD treatment on the histopathological damage of nasal mucosa and lungs. Targets of JYGBD were predicted, and the impact of JYGBD on T helper 17 (Th17) inflammation was analyzed. Peroxisome proliferator-activated receptor delta (PPARD) was artificially silenced to assess the effects of PPARD deficiency on Th17 inflammation. The regulation of PPARD on methyl-CpG-binding protein 2 (MECP2) was analyzed as well. RESULTS: JYGBD alleviated allergic conditions in rats and inhibited inflammatory cell infiltration and damage in nasal mucosa and lung tissues. The molecular targets of JYGBD were related to Th17 differentiation, and JYGBD alleviated Th17 inflammation in CARAS rats and inhibited Th17 differentiation in vitro. PPARD-mediated transcriptional inhibition of MECP2 blocked signal transducer and activator of transcription 3 (STAT3) activation to alleviate Th17/regulatory T cells (Treg) imbalance. MECP2 deletion and inhibition of STAT3 signaling alleviated PPARD knockdown-induced Th17/Treg imbalance and attenuated CARAS in rats. CONCLUSION: JYGBD induces PPARD-mediated transcriptional inhibition of MECP2 to block STAT3 signaling pathway activation, which restores Th17/Treg homeostasis to alleviate CARAS.