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

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.

N1-Methyladenosine (m1A) Regulation Associated With the Pathogenesis of Abdominal Aortic Aneurysm Through YTHDF3 Modulating Macrophage Polarization

“…It is also worth mentioning that novel chemo-photothermal synergistic therapy targeted on CD44 -positive inflammatory macrophages is being developed for the treatment of atherosclerosis ( 58 ). In addition, mTOR , a signaling molecule also called the mechanistic target of rapamycin, has been identified as a key factor in the PI3K/Akt/ mTOR or the AMPK/ mTOR signaling pathway ( 59 , 60 ). The overactivation of mTOR signaling accelerates AAA expansion via affecting the phenotype transition of VSMCs, macrophages infiltration, MMPs expression, and inflammatory cytokine production ( 61 ).…”

“…The overactivation of mTOR signaling accelerates AAA expansion via affecting the phenotype transition of VSMCs, macrophages infiltration, MMPs expression, and inflammatory cytokine production ( 61 ). Hence, mTOR is also reckoned as a potential target for AAA drug therapy including rapamycin, metformin (MET) and Gambogic acid ( 59 , 60 , 62 ). As for the integrin family (including ITGB1, ITGAV, ITGA1 , etc.…”

Mouse models for abdominal aortic aneurysm

“…inhibitor (Ortega et al, 2019), niacin (Horimatsu et al, 2019), licochalcone A, a traditional Chinese medicine (Hou, Yang, & Zheng, 2019), and gambogic acid, a derivative of resin (Liu, Shan, & Li, 2019), which inhibited AAA development. In contrast, vascular smooth muscle-specific deficiency of the alpha subunit of the heterotrimeric G stimulatory protein, responsible for receptor-stimulated cAMP generation and activation of protein kinase A pathway (Qin et al, 2019), promoted AAA formation in mouse models.…”

Aneurysms and dissections - What is new in the literature of 2019/2020 - a European Society of Vascular Medicine annual review

“…Gambogic acid is the main effective constituent of Gamboge. Liu et al demonstrated that Gambogic acid prevents angiotensin II induced AAA through inflammatory and oxidative stress dependent targeting of the PI3 K/Akt/mTOR and NF-κB signaling pathways in mice [49]. Licochalcone A (LA), a chalcone derived from liquorice, exhibits multiple biological activities, including anti-oxidation and anti-inflammation.…”