4.6 Article

Angelica sinensis Polysaccharide and Astragalus membranaceus Polysaccharide Accelerate Liver Regeneration by Enhanced Glycolysis via Activation of JAK2/STAT3/HK2 Pathway

Journal

MOLECULES
Volume 27, Issue 22, Pages -

Publisher

MDPI
DOI: 10.3390/molecules27227890

Keywords

Angelica sinensis polysaccharide; Astragalus membranaceus polysaccharide; hexokinase 2; glycolysis; JAK2; STAT3 pathway; liver regeneration

Funding

  1. National Natural Science Foundation of China [81973742]
  2. Experimental Formulary Sichuan Youth Science and technology Innovation research team [2020JDTD0022]
  3. XingLin Scholars Program of Chengdu University of TCM [QJJJ2022002, YYZX2020036]
  4. Sichuan Provincial Science and Technology Department [2021YJ0198]

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Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) can promote hepatocyte proliferation, accelerate liver regeneration, and protect the liver.
The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 mu g/mL to 3200 mu g/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.

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