## 4 Effect of PS on Cardiovascular Diseases Linked to MetS
They also reported a decreased thickness of the tunica media of aorta and decreased disruption in the arrangement of the elastic fibres in aortic tissue diabetic rats. PS leaf extract could prevent cardiac dysfunction and early signs of atherosclerosis by reducing degenerative changes in the myocardium and aortic tissues of STZ diabetic rats. There are a couple of drawbacks worth considering. All the in vitro studies did not use well-established antioxidant or anti-inflammatory agents as a positive control to verify the action of PS. Although simvastatin did not lower CRP, it did reduce VCAM and ICAMmore effectively than PS, according to a study by [PERSON] et al. [140]. The combination of PS and simvastatin may be more effective in preventing atherosclerosis than individual agents. Table 2 summarises the effect of PS on atherosclerosis linked to MetS, while Figure 6 summarises the current knowledge on the effect of PS supplementation on cardiovascular diseases linked to MetS and the further investigation required in this area. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Researcher** & **Study Design** & **Findings** \\ \hline \hline \multicolumn{3}{c}{Cell Culture Studies} \\ \hline \multirow{7}{*}{[PERSON] et al. [133]} & Cell line: HUVECs & \(\downarrow\) ICAM-1 and NF-\(\kappa\)B p65 protein expression at 150, 250, and 300 \(\upmu\)g/mL compared to negative control \\  & Mode of disease induction: TNF-\(\alpha\)-induced & 150, 250, and 300 \(\upmu\)g/mL compared to negative control \\  & Heterament: 100, 150, 250, and 300 \(\upmu\)g/mL AEPS for 24 h & \(\downarrow\) VCAM-1 protein expression compared to negative control \\  & Control: & \\  & Negative: no treatment & \\  & Positive: no & \\  & Cell line: HUVECs & \(\uparrow\) expression of eNOS mRNA compared to \\  & Mode of disease induction: H\({}_{2}\)O\({}_{2}\)-induced & negative control \\  & atherosclerosis & \(\uparrow\) eNOS protein levels compared to negative control \\  & Treatment: 150 \(\upmu\)g/mL AEPS for 24 h & control \\  & Control: & \(\uparrow\) eNOS enzyme activity compared to negative control \\  & Negative: no treatment & control \\  & Positive: no & \(\uparrow\) NO production compared to negative control \\  & Cell line: HUVECs & \(\uparrow\) NO levels compared to negative control \\  & Mode of disease induction: TNF-\(\alpha\)-induced & \(\uparrow\) DDAH1 mRNA expression, protein level, and \\  & atherosclerosis & enzyme activity compared to negative control \\  & Treatment: 150, 250, and 300 \(\upmu\)g/mL AEPS for 24 h & \(\downarrow\) ADMA level compared to negative control \\  & Control: & \\  & Negative: no treatment & \\  & Positive: no & \\ \hline \multicolumn{3}{c}{Animal Studies} \\ \hline \multirow{7}{*}{[PERSON] et al. [140]} & Animals: 42 male New Zealand White rabbits & \(\downarrow\) ICAM, VCAM, and CRP at 500 mg/kg (1.8 \(\pm\) 2 kg) & compared to negative control \\  & Mode of disease induction: HCD-induced & \\  & atherosclerosis & \\  & Treatment: 62.5, 125, 250, and 500 mg/kg/day of & \\  & AEPS for 10 weeks & \\  & Control: & \\  & Negative: no treatment & \\  & Positive: simvastatin (1.2 mg/kg) for 10 weeks & \\  & Animals: 42 male New Zealand White rabbits & \(\downarrow\) atherosclerotic lesions and fat deposit in the \\  & (1.8 \(\pm\) 2 kg) & \\  & Mode of disease induction: HCD-induced & \\  & atherosclerosis & \\  & Treatment: 62.5, 125, 250, and 500 mg/kg/day of & \\  & AEPS for 10 weeks & \\  & Control: & \\  & Negative: no treatment & \\  & Positive: simvastatin (1.2 mg/kg) for 10 weeks & \\  & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Effect of PS on atherosclerosis and cardiovascular complications due to MetS.