Flavonoids from aging tangerine peel alleviate OVA-induced allergic asthma through JAK/STAT signaling pathway in balb/c mice

The dry pericarp of the fruit of Citrus reticulata Blanco cultivar ‘Chachi’ is known as Guang ChenPi (GCP) in Guangdong province in China, which should be stored for more than three years for optimal bioactivity, especially for spleen-strengthening and cough relief. However, the molecular mechanisms and the impact of aging years on bioactivity in cough relief remain poorly understood. Herein, we investigate the efficacy of GCP of different aging years using an allergic asthma Balb/c mouse model in which airway hyperreactivity was induced by ovalbumin (OVA). The results showed that aqueous extracts of GCP of different aging years could reduce lung inflammation and airway tissue lesion, and could inhibit the expression of tracheal MUC5AC protein, IL-4, IL-5, and IL-13 mRNA levels in lung tissue and bronchoalveolar lavage fluid (BALF) through the JAK/STAT pathway. Furthermore, we have identified 11 constituents absorbed in blood based on UHPLC-Orbitrap MS/MS and metabolism results showed that linoleic acid metabolism and sphingolipid signaling pathways are the primary mechanisms of the effort. The Grey correlation degree indicated the top three constituents of tangeretin, quinic acid and 2’,5,6-trimethoxyflavone, which were closely related to the effects of drying dampness and phlegm elimination. Importantly, our findings underscored that GCP of different aging years showed good efficacy in rescuing IL-13 and IL-4 levels in serum and BALF. This study provides new evidence that flavonoids in aging GCP could modulate activity towards alleviating OVA-induced allergic asthma through the JAK/STAT pathway.