Yunyao Qilongtian alleviates the progression of COPD by regulating HMGB1 and inhibiting AMPK/mTOR/ULK1 pathway induced mitophagy

Abstract

Background: Qilongtian is a traditional Chinese medicine compound with Yunnan medical characteristics. Its main components have the effect of inhibiting inflammation. Inflammatory response is closely related to the progression of Chronic obstructive pulmonary disease (COPD). Therefore, this study is mainly to confirm the influence and mechanism of Yunyao Qilongtian on pulmonary phlogosis and airway remodeling with COPD in patients. Methods: In this study, using Wright Giemsa staining to measure the number of neutrophils in bronchoalveolar lavage fluid (BALF). Through ELISA assay, IL-β, IL-6 and TNF-α were detected in BALF. Expect that, we used HE staining to detect the Lung histological changes. Collagen deposition in or near the trachea was detected by Masson staining. Through Western blot assay, the proteins of the Mitochondrial autophagy and AMPK/mTOR/ULK1 signaling pathway were detected. The level of HMGB1, 8-OHdG and 4-HNE was detected by immunohistochemistry. Mitochondrial autophagy was detected by LC3 and MTR double immunostaining. Membrane potential was measured by JC-1staining. MitoSOX evaluates the production of mtROS. Cx I, II, III, and IV activity assay kit assay for the activity. ATP concentration was detected by ATP detection kit. Results: Qilongtian significantly attenuated cigarette smoke (CS) -induced lung inflammation and airway remodeling, as well as the mitophagy and mitochondrial dysfunction of CS-induced. Qilongtian alleviated CS-induced HMGB1 upregulation. Overexpression of HMGB1 partially restored the protective effect of Qilongtian on lung inflammation and airway remodeling in COPD. As an inhibitor of the AMPK/mTOR/ULK1 pathway, AMPKi could partially restored the influence of OE-HMGB1. Conclusion: Yunyao Qilongtian alleviates COPD lung inflammation and airway remodeling by inhibiting HMGB1 to inhibit excessive mitochondrial autophagy induced by AMPK/mTOR/ULK1 signaling pathway.