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

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 deltaisomerase 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.

Efficacy of the Panax Notoginseng Ejiao Suppository in the Treatment of Patients with Ulcerative Proctitis and Its Effect on Inflammatory Response and Immune Function

“…In a rat model of colitis induced by sodium dextran sulfate, the use of Panax notoginseng ethanol extract promotes the repair of colonic mucosa and microvascular damage in rats with colitis, reduces the inflammatory response, and lowers the disease activity scores [ 20 ]. In addition, in a colitis rat model, Panax notoginseng extract upregulates the expression of ATP4a in mitochondria in colonic mucosal epithelial cells to improve glycolysis, which is strongly associated with the activation of mitochondrial aerobic oxidation [ 21 ].…”

20(S)‐Protopanaxadiol saponins isolated from Panax notoginseng target caveolin‐1 against intestinal barrier dysfunction by alleviating inflammatory injury and oxidative stress in experimental murine colitis

“…In addition, studies have reported that components derived from P. notoginseng have many healthcare functions, including cardiovascular protection, neuroprotection, and anticancer and antidiabetic effects (Xu et al., 2019). Furthermore, it is also reported to prevent colonic mucosal injury and inflammation resulting from UC through pyruvate dehydrogenase kinase 4 and gut microbiota (He, Pan, et al., 2022; Wang et al., 2023). The most abundant active ingredients in P. notoginseng are P. notoginseng saponins (PNS), the dammarane‐type saponins, including protopanaxadiol‐type and protopanaxatriol‐type (Liu et al., 2020).…”