PI3K/AKT/SERBP-1 pathway regulates Alisma orientalis beverage treatment of atherosclerosis in APOE-/- high-fat diet mice

Pharm Biol. 2023 Dec;61(1):473-487. doi: 10.1080/13880209.2023.2168020.

Abstract

Context: Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear.

Objective: As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS.

Materials and methods: Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE-/- mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver.

Results: Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB's treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE-/- mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE-/- mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%).

Conclusions: AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.

Keywords: Traditional Chinese medicine; aortic plaque; high-fat diet; lipid metabolism; network pharmacology.

MeSH terms

  • Alisma* / metabolism
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / pharmacology
  • Apolipoproteins E / therapeutic use
  • Atherosclerosis* / drug therapy
  • Diet, High-Fat / adverse effects
  • Lipids
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plaque, Atherosclerotic* / drug therapy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sterol Regulatory Element Binding Protein 1 / pharmacology

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Sterol Regulatory Element Binding Protein 1
  • Lipids
  • Apolipoproteins E

Grants and funding

The study was supported by the National Natural Science Foundation of China [82074292] , Jiangsu Traditional Chinese Medicine Science and Technology Development Plan (No. QN202202) Funded by Yushan scholarly sect Classic Traditional Chinese Medicine Classic Inheritance Award Fund.