Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus

Abstract

Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia.

Discussing the Mechanism of Dahuang Huanglian Xiexin Decoction in the Treatment of Type 2 Diabetes Mellitus via Network Pharmacology and Molecular Docking

“…Some studies found that HIF-1α gene expression in T2DM patients with poor metabolic control was decreased [33]. However, some studies showed that the level of HIF-1α in T2DM patients was signi cantly higher than that in the control group, and insulin secretion increased when hypoxia was inhibited [34]. Therefore, the effect of HIF-1 signaling pathway on T2DM is not completely clear, which needs to be further con rmed.…”

Effects of Tang Shen 2 Hao Fang, a Traditional Chinese Medicine, on Diabetic Nephropathy in Sprague–Dawley Rats

“…and Herba lycopi were shown to improve T2D in diabetic mice with nephropathy. 35,36 Cicada slough reduces IgA nephropathy, 37 an immune-mediated inflammatory condition of the glomerulus. 38 With its antiinflammatory and antioxidant effects and the capability to lower blood glucose and blood lipids by different mechanisms, the combination of components in this natural traditional Chinese remedy partially remedied disease-causing diabetic kidney injury in rats.…”

Pseudostellaria heterophylla Extract Polysaccharide H-1-2 Suppresses Pancreatic Cancer by Inhibiting Hypoxia-Induced AG2

“…Notably, H-1-2 treatment also suppressed HIF1a protein levels (Figures 4B and 4D), confirming the previously reported anti-hypoxic property of H-1-2. 10,12 H-1-2 Downregulates AGR2 Expression through the Hypoxia-Responsive Element (HRE) in Its Promoter Region HIF1a was reported to promote AGR2 expression via the HRE from À937 to À912 bp on the AGR2 promoter sequence. 13 To experimentally interrogate the modulation of AGR2 expression by HIF1a, we constructed wild-type or mutated HRE-fused luciferase reporter plasmids (Figure 5A).…”

“…H-1-2, a novel homogeneous polysaccharide, was recently isolated from the polysaccharide fractions of the P. heterophylla extracts, 11 which was later shown to inhibit hypoxia in human pancreatic b cells. 12 These studies have prompted us to hypothesize that polysaccharide H-1-2 might exert the same anti-hypoxic activity in pancreatic cancer cells and suppress tumor progression. In addition, we sought to elucidate the downstream molecular mechanism responsible for the inhibitory effect of H-1-2 on pancreatic cancer.…”