Mulberry Leaf and Neochlorogenic Acid Alleviates Glucolipotoxicity-Induced Oxidative Stress and Inhibits Proliferation/Migration via Downregulating Ras and FAK Signaling Pathway in Vascular Smooth Muscle Cell

Nutrients. 2022 Jul 22;14(15):3006. doi: 10.3390/nu14153006.

Abstract

Mulberry leaf (Morus alba L.) has been used as a health food and in traditional medicine to treat several metabolic diseases, including diabetes, hypertension, and hyperlipidemia. However, the mechanism by which mulberry leaf and its functional components mediate atherosclerosis remains unclear. This study aimed to determine the effect of mulberry leaf extract (MLE) and its major component, neochlorogenic acid (nCGA), on the proliferation and migration of rat aortic vascular smooth muscle cells (VSMCs, A7r5 cell line) under diabetic cultured conditions (oleic acid and high glucose, OH). Our findings showed that MLE and nCGA significantly inhibited cell proliferation and migration in A7r5 cells as determined by a scratch wound assay and a Transwell assay. Furthermore, we observed MLE and nCGA inhibited cell proliferation and migration, such as reducing the phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), focal adhesion kinase (FAK), and small GTPase proteins using Western blot analysis. In conclusion, we confirmed the anti-atherosclerotic effects of MLE and nCGA in reducing vascular smooth muscle cell (VSMC) migration and proliferation under diabetic cultured conditions via inhibition of FAK/small GTPase proteins, PI3K/Akt, and Ras-related signaling.

Keywords: FAK signals; VSMC migration and proliferation; diabetic atherosclerosis; mulberry leaf extract; neochlorogenic acid.

MeSH terms

  • Animals
  • Atherosclerosis* / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chlorogenic Acid / analogs & derivatives
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Monomeric GTP-Binding Proteins* / metabolism
  • Morus*
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinic Acid / analogs & derivatives
  • Rats
  • Signal Transduction

Substances

  • Plant Extracts
  • Quinic Acid
  • Chlorogenic Acid
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Monomeric GTP-Binding Proteins
  • 5'-O-caffeoylquinic acid

Grants and funding

This study was supported by a grant from Chung Shan Medical University Hospital, Taichung, Taiwan (grant no. CSH-2019-C-022 and CSH-2021-C-034), and the Taiwan Ministry of Science and Technology (110-2320-B-040-010).