The Effect of Compounds Isolated from Nannochloropsis sp. Microalgae on PON1 and HDL Activities

Atherosclerosis is a chronic disease that is characterized by accumulation within the intima of the arterial wall of lipids and oxidized lipids. High density lipoprotein (HDL) plays an important role in preventing atherosclerosis (AS). The antioxidant effect of HDL is mostly associated with paraoxonase (PON1) activity. PON1 hydrolyzes oxidized lipids, oxidized low density lipoprotein (LDL) and thus protects against atherosclerosis development, also PON1 was shown to be responsible for some of the HDL antiatherogenic characteristics such as HDL-mediated cholesterol efflux from macrophages. Thus, increasing PON1 activities may improve HDL functions and quality and decrease atherosclerotic risk.

In our laboratory we found that the ethanol extract of Nannochloropsis sp. microalgae (ethanol: water 70:30%) increased PON1 activity. The active compound was isolated and identified. The effect of the isolated compound on rePON1lactonase and esterase activity was examined. It was increased rePON1 activity by a dose and time respond manner and preserve its activity for at least 48 hours. In addition, the isolated compound was increased human serum PON1 lactonase activity by a dose respond manner after incubation for 4 hours at 37˚C.

Using tryptophan-fluorescence-quenching assay, we found that the isolated compound interact with rePON1 spontaneously with negative free energy (ΔG=-22.87 KJ/mole at 25˚C) and high affinity (Ka= 1.05*10⁴ M^-1). Molecular modeling calculations show that the main interaction is a hydrogen bond with a support of van der Waals interactions.

Furthermore, the isolated compound increased the HDL cholesterol efflux from macrophages by a dose dependent manner.

Our findings suggest that Nannochloropsis sp. microalgae containing agents with a potential role in decreasing Atherosclerosis risk by improving HDL quality. The isolated agent can increase PON1 activity and HDL cholesterol efflux, both are antiatherogenic effects.