Dual-Directional Regulation of Belamcanda chinensis Extract on Ovalbumin-Induced Asthma in Guinea Pigs of Different Sexes Based on Serum Metabolomics

Abstract

To explore the potential biomarkers and metabolic pathways underlying the anti-asthma effects of Belamcanda chinensis extract, this study established an ovalbumin-induced allergic bronchial asthma model in guinea pigs. Sixty guinea pigs were randomly divided into the blank control group, model control group, Belamcanda chinensis extract groups (0.8 g/kg, 1.2 g/kg, 1.6 g/kg, respectively), and dexamethasone acetate tablet group (0.5 mg/kg). Starting on the 22nd day, the drugs were administered by gavage for seven consecutive days. Serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of IL-4 and IgE in the serum and IFN-γ and TNF-α in the BALF were detected by ELISA. UPLC-MS was combined with multivariate statistical analyses, including partial least squares discriminant analysis (PLS-DA), and differential metabolites between groups were identified. Metabolic pathway analysis was performed by querying the KEGG (Kyoto Encyclopedia of Genes and Genomes) online database. Female and male guinea pigs were analyzed. The results showed that compared with the model group, the IgE and IL-4 serum levels were significantly decreased in the 1.6 g/kg group, and the IFN-γ level in the BALF was significantly increased. The TNF-α level was significantly decreased in the 1.2 g/kg and 1.6 g/kg groups. There were 39 common differential metabolites among females and males, and 37 differential metabolites showed opposite regulatory trends in the serum of guinea pigs with asthma and after treatment, mainly involving 17 metabolic pathways, such as pantothenate and CoA biosynthesis, the arachidonic acid mechanism, and glycerophospholipid metabolism. Belamcanda chinensis extract improved OVA-induced asthma, as determined based on immune mechanisms, inflammation, nerve metabolism, and energy metabolism. The serum levels of metabolites produced by the model animals exhibited distinct sex-specific differences, and the treatment effect of Belamcanda chinensis extract also showed sex-specific differences and bidirectional regulation.