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

ABSTRACT: 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 μg/mL to 3200 μg/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.

SUBMITTER: Wen XD

PROVIDER: S-EPMC9695464 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Wen Xu-Dong XD Zhang Yao-Lei YL Yang Ling L Ye Zhen Z Fu Guo-Chuan GC Hu Yong-He YH Pan Tao T Ye Qiao-Bo QB

Molecules (Basel, Switzerland) 20221115 22

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 ...[more]

PMID: 36431990

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Project description:BackgroundAstragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach.MethodsAM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above.ResultThe overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets.ConclusionsAltogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.

Dataset Information

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

Publications

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

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