Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease

Ting Meng; Feng-Sen Li; Dan Xu; Jing Jing; Zheng Li; Miyesier Maimaitiaili; Yong-Jiang Bao

doi:10.21037/jtd-23-1115

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease

J Thorac Dis. 2024 Apr 30;16(4):2326-2340. doi: 10.21037/jtd-23-1115. Epub 2024 Apr 16.

Authors

Ting Meng^{1

2}, Feng-Sen Li^{1

3}, Dan Xu³, Jing Jing³, Zheng Li³, Miyesier Maimaitiaili², Yong-Jiang Bao²

Affiliations

¹ College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China.
² Department of General Medicine, The Eighth People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
³ Department of Respiratory, The Fourth Affiliated Hospital of Xinjiang Medical University, National Clinical Research Base of Traditional Chinese Medicine, Urumqi, China.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD.

Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC), FEV₁, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected.

Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment.

Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Keywords: Chronic obstructive pulmonary disease (COPD); Sirtuin 5 (SIRT5); Yiqigubiao pill (YQGB pill); mitochondrial function.