## 3 Results
### The Plant Extracts Reduce Lipid Accumulation in the Metabolically Challenged Hepatocytes
(**d**) Immunoblotting detection of enzymes engaged in lipid metabolism in the HepG2 lysates: FAS—fatty acid synthase; ATP-CL—ATP citrate lyase; ACAD9—long chain acyl-CoA dehydrogenase 9; m—mitochondrial, c/n—cytoplasmic/nuclear form; ACSL1—long chain acyl-CoA synthetase 1. Probing for \(\upbeta\)-actin serves as a loading control. The numbers below the protein bands express the band intensity normalised to \(\upbeta\)-actin in relation to the control (Con = 100%). RL—sea buckthorn extract (50 \(\upmu\)g/mL); RO—sea buckthorn fruit extract (50 \(\upmu\)g/mL); DL—Cornelian cherry leaf extract (50 \(\upmu\)g/mL); DO—Cornelian cherry fruit extract (50 \(\upmu\)g/mL); Con—cells treated with the appropriate amount of solvent. Panels (**b,c**) created with [[https://www.biorender.com/](https://www.biorender.com/)]([https://www.biorender.com/](https://www.biorender.com/)). Liver plays a central role in intermediary lipid metabolism in both fed and fasted conditions, facilitating storage or release of fats and distribution to peripheral tissues when needed. Therefore, hepatocytes abundantly synthesise enzymes involved in fatty acid anabolism, such as fatty acid synthase (FAS) and ATP-citrate lyase (ATP-CL); in mitochondrial fatty acid oxidation, such as acyl-CoA dehydrogenase 9 (ACAD9); as well as proteins that control or engage in lipid turnover in both anabolic and catabolic directions, such as lipin 1 and long-chain acyl-CoA synthetase 1 (ACSL1). Having observed that sea buckthorn and Cornelian cherry extracts affect lipid accumulation in metabolically challenged hepatocytes, we checked the levels of the mentioned proteins in HepG2 cells treated with the extracts. RL, RO and DO extracts downregulate FAS, whereas they increase ATP-CL (Figure 3d). RO, DL and DO extracts increase the level of the higher molecular weight precursor form of ACAD9, which can also be found in the cytoplasm and nucleus (ACAD9 c/n). On the other hand, they decrease the level of the mitochondrial ACAD9 (m) form (Figure 3d). All the extracts applied in higher concentrations (50 ug/mL) reduce lipin 1 level; the only extract that upregulates this protein is RO at a concentration of 10 ug/mL (Figure 3d). RL extracts in both concentrations decrease ACSL1, whereas the other extracts do not seem to alter this protein expression significantly (Figure 3d). Taken together, the sea buckthorn and Cornelian cherry extracts do have an impact on the enzymes that control lipid metabolism, but their influence is multidirectional. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline
**Treatment** & **n** & \ \begin{tabular}{c} **Mean Area** \\ **[\(\mu\)m\({}^{2}\)]** \\ \end{tabular}  & **Median** & **Min** & **Max** & \begin{tabular}{c} **Coefficient** \\ **of Variation** \\ \end{tabular}  & **Skewness** & **Kurtosis** \\ \hline HG & & & & & & & & \\ Con & 438 & 1.92 & 1.07 & 0.20 & 45.27 & 151.57 & 8.54 & 115.41 \\ RL & 460 & 1.61 & 0.98 & 0.20 & 14.46 & 115.78 & 2.91 & 11.67 \\ RO & 455 &  
The Plant Extracts Do Not Affect oxLDL Phagocytosis, but Modulate Monocyte Innate Response Activities  
Bearing in mind this connection between metabolic reprogramming, lipid uptake and inflammatory phenotype, we decided to check how the sea buckthorn and Correlian cherry extracts influence monocyte oxLDL phagocytosis, lipid metabolizing enzymes as well as IL-1 \(\beta\) and NO production. Preincubation with plant extracts prior to exposure to oxLDL had no influence on phagocytosis (Figure 4a,b). The extracts influenced the levels of enzymes involved in lipid metabolism in quite a diverse way: sea buckthorn leaf extracts (RL 10 and 50 \(\mu\)g/mL) FAS and ATP-CL were modulated in opposite directions and increased FAS was accompanied by decreased ATP-CL and vice versa (Figure 4c). This suggests the existence of a kind of compensatory mechanism. The RL extract in higher concentrations (50 \(\mu\)g/mL) upregulated the mitochondrial ACAD9 level (Figure 4c), which might indicate redirection to fatty acid oxidation and oxidative metabolism in general.