Panax notoginseng attenuates hypoxia-induced glycolysis in colonic mucosal epithelial cells in DSS-induced colitis

Wei He; Huafeng Pan; Ping Tao; Jiang Lin; Beiping Zhang; Shiying Wang

doi:10.21037/atm-22-566

Panax notoginseng attenuates hypoxia-induced glycolysis in colonic mucosal epithelial cells in DSS-induced colitis

Ann Transl Med. 2022 Feb;10(4):218. doi: 10.21037/atm-22-566.

Authors

Wei He¹, Huafeng Pan¹, Ping Tao², Jiang Lin³, Beiping Zhang², Shiying Wang^{1

2}

Affiliations

¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
² Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
³ Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Background: Colonic mucosal injuries are an important manifestation of ulcerative colitis (UC), which is related to hypoxia-induced glycolysis in colonic mucosal epithelial cells (cmECs). Panax notoginseng (PN) promotes the repair of colonic mucosal injuries by inhibiting hypoxia-induced glycolysis in cmECs; However, the mechanism by which this occurs is not completely clear. Here, we are to investigate the effects of PN on glucose metabolism in cmECs in colitis and the underlying mechanism.

Methods: A model of dextran sulfate sodium-induced colitis rats was used in this research, and the severity of colitis was assessed by pathology, disease activity index (DAI), and weight changes. The content of intracellular pyruvate, intracellular lactate, adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial ROS (mtROS), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and inflammatory cytokines was detected by assay kits. The expression levels of proteins were detected by western blotting. The expression levels of the ATP4a gene were detected by quantitative polymerase chain reaction (QT-PCR).

Results: The colonic mucosal injuries of the colitis rats were significantly worse than those of the control group. Specifically, the hypoxia-induced glycolysis and potential of hydrogen (pH) in the colonic lumen were increased, and the expression of ATP4a was downregulated in the colitis rats. PN (1.0 g/kg) promoted the repair of colonic mucosal injuries, and reversed the pH in the colonic lumen. Further, PN increased the expression of ATP4a proteins, the content of ATP, and the SOD activity, and decreased the expression of pyruvate dehydrogenase lipoamide kinase isozyme and hypoxia-inducible factor 1-alpha proteins, the content of ROS, and MPO activity in cmECs in colitis. PN also increased the expression of ATP4a, cytochrome P450 family 21 subfamily a member 2, and hydroxy-delta-5-steroid dehydrogenase, 3 beta and steroid delta-isomerase 2 proteins in the mitochondria, and decreased the content of mtROS in cmECs.

Conclusions: PN alleviated the pH in the colonic lumen and hypoxia-induced glycolysis in cmECs by reducing the hypoxia-induced glycolysis caused by the downregulation of ATP4a protein, thereby promoting the repair of colonic mucosal injuries in colitis.

Keywords: ATP4a protein; Panax notoginseng (PN); glycolysis; hypoxia; ulcerative colitis.