## 3 Pharmacological Properties of GP
### Anti-Atherogenic Effect  
Accumulating evidences had demonstrated that GP could be developed as potential and promising agents for atherosclerosis (AS) treatment. The detailed parameters of experiments including experimental models, dosage, and possible mechanisms were listed in Table 2. The anti-atherogenic mechanisms are shown in Figure 6, which were mainly related to the reduction of foam cell formation, inflammation, DNA damage, and endothelial cells (ECs) apoptosis and the increasement of autophagy and cholesterol flux. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Active Composition** & **Models** & **Dosage** & **Activity/Mechanism** & **Ref. ** \\ \hline \multirow{6}{*}{Gypenoside XVII (GP-17)} & A high-fat diet-induced & \multirow{3}{*}{50 mg/kg for 10 weeks, i.g.} & \multicolumn{2}{c}{Decreased blood lipid levels, increased the expression of antioxidant enzymes (SOD, GSH-Px, CAT) and decreased the MDA level in serum, decreased atherosclerotic lesion size.} \\  & AS model in ApoE-/- mice & & Reduced the ROS generation, protected HUVECs \\  & AS model in ApoE-/- mice & 6.25, 12, 25, 50, & against Ox-LDL-induced apoptosis and oxidative stress, increased the expression of ER\(\alpha\), alleviated atherosclerosis via the ER\(\alpha\)-mediated & \\  & AS model in ApoE-/- mice & & Dlown-regulated the expression of the receptor of CD36 in macrophages, up-regulated the expression of the receptor of ABCA1, LXR-\(\alpha\), PPAR-\(\alpha\) in macrophages, then reduced the intake of Ox-LDL in macrophages, andpromoted the efflux of Intracellular cholesterol. \\  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Active Composition** & **Models** & **Dosage** & **Activity/Mechanism** & **Ref. ** \\ \hline GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 g/kg for 4 weeks, i.g. & Lowered the levels of TG, TC and LDL-C, elevated HDL-C level, reduced atheromatous plaques in aortic canal, increased the expression of ULK1, Beclin1 and LC3, decreased p-mTOR expression, relieved the formation of atherosclerotic plaque and prevented atherosclerosis possibly through regulating the autophagy. & [53] \\ GPS & A high-fat diet-induced AS model in SD mice & 40, 80, 160 mg/kg for 7 weeks, i.g. & Inhibited the expression of ICAM-1, MCP-1 and NF-kB P56, delayed the process of atherosclerosis. & [54] \\ \hline GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 mg/kg for 7 weeks, p.o. & Enhanced PI3K and p-Akt expression and down-regulated expression of p-Bad, cytochrome c, cleaved caspase 3, cleaved caspase 9, down-regulated DRP1 and Mfn2 protein levels, inhibited the formation of atherosclerosis via the PI3K/Akt/Bad pathway. & [55] \\ GPS & Cholesterol-induced DNA damage in HUVECs & 1, 10 and 100 mg/mL & Decreased the expression of NOX4 and inhibited ROS production, increased the activity of NOS, decreased the \(\gamma\)H2 AX expression, alleviated DNA damage. & [56] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 g/kg for 4 weeks, i.g. & Increased the expression of Clock, Bmal1, Period 1, Period 2, Cry1 and Cry 2 proteins, alleviated the formation of atherosclerotic plaque. & [57] \\ \hline \multirow{4}{*}{GPS} & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of OPA1 and downward-regulated expression of Fission1, increased ATP level, increased the activity of respiratory chain enzyme complexes I, II, III, IV and V, protected ECs by affecting mitochondrial energy metabolism and fusion lysis. & [59] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 g/kg for 4 weeks, i.g. & Increased the expression of autophagosome related proteins Atg3, Atg4c, Atg5, Atg12, promoted the formation of autophagosome, reduced the serum lipid level. & [60] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 g/kg for 4 weeks, i.g. & Increased the expression of TLR4, MyD8, NF-kB, proteins Atg3, Atg4c, Atg5, Atg12, promoted the formation of autophagosome, reduced the serum lipid level.