Pinellia ternata attenuates carotid artery intimal hyperplasia and increases endothelial progenitor cell activity via the PI3K/Akt signalling pathway in wire-injured rats

Pharm Biol. 2020 Dec;58(1):1184-1191. doi: 10.1080/13880209.2020.1845748.

Abstract

Context: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) (PT) has been widely used in the treatment of atherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood.

Objective: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia.

Materials and methods: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups (n = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT+LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT) and endothelial progenitor cells (EPCs) (with injection of 5 × 105/cells), and treated for 4 or 8 weeks.

Results: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL+/FITC-UEA-1+ population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in the blood, decreased TCHO, TG, LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in the blood. However, these changes were reversed by the PI3K/Akt pathway inhibitor LY294002.

Discussion and conclusions: PT can be developed as an atherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on the effects of PT on intimal hyperplasia in wire-injured atherosclerosis patients and explore in depth some other relevant molecular mechanisms.

Keywords: Atherosclerosis; EPCs; blood lipids; inflammatory response.

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • Carotid Artery Injuries / drug therapy*
  • Carotid Artery Injuries / pathology*
  • Cytokines / metabolism
  • Endothelial Progenitor Cells / drug effects*
  • Hyperplasia
  • Hypolipidemic Agents / pharmacology
  • Male
  • Nitric Oxide Synthase Type III / biosynthesis
  • Oncogene Protein v-akt / drug effects
  • Oncogene Protein v-akt / metabolism*
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pinellia / chemistry*
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Tunica Intima / pathology*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Cytokines
  • Hypolipidemic Agents
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Oncogene Protein v-akt

Grants and funding

This work was supported by grants from the Medical Scientific Research Foundation of Guangdong Province, China (B2019068); and the Administration of Traditional Chinese Medicine of Guangdong Province, China [Grant numbers 20173024 and 20181012].