The Endothelial Protective Properties of Essential Oil from Fructus Alpiniae zerumbet via the Akt/NOS-NO Signaling Pathway In Vitro

Abstract

Oxidized low-density lipoprotein has been demonstrated to induce vascular injury, at least partly, through the nitric oxide-dependent pathway. Our previous studies showed that the essential oil from Fructus Alpiniae zerumbet had a capacity of antioxidation to ameliorate endothelial function and vasodilatation on aortic rings ex vivo. The present study aims to confirm the hypothesis that Fructus Alpiniae zerumbet protects against oxidized low-density lipoprotein-induced endothelial dysfunction in human aortic endothelial cells, and the role nitric oxide synthase plays in the process. Human aortic endothelial cells were pretreated with one of three different doses of Fructus Alpiniae zerumbet (1, 2, or 4 µg/mL), simvastatin (10 µM), or vehicle,followed by coincubation with oxidized low-density lipoprotein (150 µg/mL), for designed time periods. Exposure to oxidized low-density lipoprotein resulted in cytotoxicity accompanied by mitochondrial membrane potential collapse, excessive reactive oxygen species generation, and a decrease of nitric oxide production. The upregulation of inducible nitric oxide synthase mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Furthermore, oxidized low-density lipoprotein inhibited Akt phosphorylation and downregulated endothelial nitric oxide synthase and soluble guanylatecyclase in mRNA expression and the protein level. However, cytotoxicity and aberrant reactive oxygen species and nitric oxide generation caused by oxidized low-density lipoprotein could be significantly inhibited by Fructus Alpiniae zerumbet or Sim pretreatment. Results from this study confirmed that Fructus Alpiniae zerumbet could protect against oxidized low-density lipoprotein-induced endothelial dysfunction by antioxidation and modulating the Akt/nitric oxide synthase-nitric oxide signaling pathway.

Phytochemicals of Alpinia zerumbet: A Review

“…The chemical constituents in the essential oils of A. zerumbet fruits have been reported by the groups of Shen et al [ 88 , 92 ], Feng et al [ 53 ], and Hou et al [ 87 ]. The group of Shen et al [ 88 , 92 ] identified 58 volatile compounds in the essential oils of A. zerumbet fruits collected from China. The major components were camphene (10.1%), β-pinene (15.1%), β-phellandrene (16.4%), and 1,8-cineole (11.0%) [ 88 , 92 ].…”

“…The group of Shen et al [ 88 , 92 ] identified 58 volatile compounds in the essential oils of A. zerumbet fruits collected from China. The major components were camphene (10.1%), β-pinene (15.1%), β-phellandrene (16.4%), and 1,8-cineole (11.0%) [ 88 , 92 ]. Feng et al [ 53 ] identified 1,8-cineole (8.8%) in the essential oils obtained from A. zerumbet fruits collected in Guizhou Province (China) in July 2017.…”

<b><i>Alpinia zerumbet</i></b> and Its Potential Use as an Herbal Medication for Atherosclerosis: Mechanistic Insights from Cell and Rodent Studies

“…In addition, apoptosis of intraplaque small vessels, including endothelial cells, has been implicated in the pathogenesis of atherosclerosis [42]. EOFAZ can significantly inhibit ox-LDL-induced endothelial dysfunction in HAECs via the Akt/NOS-NO signaling pathway, and the results indicate that unbalanced NOS-NO bioavailability is involved in oxidative stress to a certain degree [43]. HAECs are pretreated with EOFAZ (1, 2, or 4 µg/mL) for 2 h and coincubated with ox-LDL (150 µg/mL) for another 12 or 24 h. The results confirm that EOFAZ inhibit LDH release in a dose-dependent manner, especially in high-dosage groups.…”

Essential Oil from Fructus Alpiniae Zerumbet Protects Human Umbilical Vein Endothelial Cells In Vitro from Injury Induced by High Glucose Levels by Suppressing Nuclear Transcription Factor-Kappa B Signaling

“…Recent in vitro studies have shown that the essential oil of FAZ (EOFAZ) can protect endothelial cells from injury, and exhibits a wide range of pharmacological properties, including anti-inflammatory effects, protection against cardiovascular diseases, and antioxidant activity [20,21]. Also, we have previously shown that EOFAZ could reduce vascular endothelial cell injury using a variety of injurious agents [22]. …”