Protective effects of Astragalus polysaccharides against paraquat-induced idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease associated with an extremely poor prognosis. The protective effect of Astragalus polysaccharides (APs) on paraquat (PQ)-induced IPF in rats is not yet clear. APs significantly improved the physiological status of IPF rats, alleviated body weight loss, and increased survival rate. APs reduced the lung index and pulmonary hydroxyproline (HYP) content, enhanced superoxide dismutase (SOD), malondialdehyde (MDA), restored cytokine levels, and attenuated alveolar inflammation and extracellular collagen deposition. Moreover, 16 S rRNA sequencing analysis revealed that APs improved the abundance of Firmicutes and Actinobacteria , inhibited the abnormal proliferation of Bacteroidetes , and reshaped gut homeostasis. Furthermore, non-targeted metabolomics found that APs down-regulated metabolites, including proline and 5,6‑dihydrouracil, while up-regulating uracil, beta‑alanine, carnosine, and beta‑aminoisobutyrate. The results of western blotting showed that APs could up-regulate the expression levels of key proteins in the β‑alanine metabolic pathway, including UPB1, ABAT, CNDP1, and CARNS1. This study provides important references for the development of APs as natural anti-inflammatory ingredients or intestinal microbiota regulators in the pharmaceutical field.