Gambogic acid prevents angiotensin II‑induced abdominal aortic aneurysm through inflammatory and oxidative stress dependent targeting the PI3K/Akt/mTOR and NF‑κB signaling pathways

Mol Med Rep. 2019 Feb;19(2):1396-1402. doi: 10.3892/mmr.2018.9720. Epub 2018 Dec 4.

Abstract

Gamboge is the dry resin secreted by Garcinia hanbaryi Hook.f, with the function of promoting blood circulation and anti‑cancer effects, detoxification, hemostasis and killing insects. It is also used for the treatment of cancer, brain edema and other diseases. Gambogic acid is the main effective constituent of Gamboge. The present study tested the hypothesis that the effect of Gambogic acid prevents angiotensin II‑induced abdominal aortic aneurysm (AAA), and explored its underlying mechanism. It was demonstrated that gambogic acid significantly inhibited AAA incidence rate, and reduced edge leading aortic diameter and aortic wall thickness in AAA mice. Gambogic acid treatment markedly decreased the levels of proinflammatory cytokines and oxidative stress factors, and transforming growth factor‑β (TGF‑β) and matrix metalloproteinase (MMP)‑2 and MMP‑9 protein expression in AAA mice. Furthermore, Gambogic acid decreased expression of phosphatidylinositol 3‑kinase (PI3K), and phosphorylation of protein kinase B (Akt), mechanistic target of rapamycin (mTOR) and p70‑S6 kinase 1. It also suppressed nuclear factor (NF)‑κB protein expression in AAA mice. The findings of the present study indicated that Gambogic acid prevents angiotensin II‑induced AAA through inflammatory and oxidative stress‑dependent targeting of the PI3K/Akt/mTOR and NF‑κB signaling pathways.

Keywords: gambogic acid; abdominal aortic aneurysm; phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin; nuclear factor-κB.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Aortic Aneurysm, Abdominal / chemically induced*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Garcinia / metabolism
  • Inflammation / metabolism*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism
  • Xanthones / pharmacology*

Substances

  • NF-kappa B
  • Xanthones
  • Angiotensin II
  • gambogic acid
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9