## 3 Pharmacological Properties of GP
### Anti-Atherogenic Effect
& [61] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 2.973 g/kg for 4 weeks, i.g. & Inhibited the expression of NF-kB via ROS scavenging and reduced the production of inflammatory cytokines. & [62] \\ 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, TNF-\(\alpha\), alleviated the inflammatory response. & [61] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 10, 50, 100 and 200 mg/mL & Inhibited the activation of NF-kB via ROS scavenging and reduced the production of inflammatory cytokines. & [62] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of TLR4, MyD8, NF-kB, TNF-\(\alpha\), alleviated the inflammatory response. & [63] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of the TLR4, MyD8, NF-kB, TNF-\(\alpha\), alleviated the inflammatory response. & [61] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of the TLR4, MyD8, NF-kB, TNF-\(\alpha\), alleviated the inflammatory response. & [61] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of the TLR4, MyD8, NF-kB, TNF-\(\alpha\), alleviated the inflammatory response. & [62] \\ GPS & A high-fat diet-induced AS model in ApoE-/- mice & 100 mg/mL & Increased the expression of the TLR4, MyD8, NF-Inflammation occurred at different stages of AS progression. Therefore, anti-inflammatory therapy had become an important intervention to delay the progression of the disease. Recent studies had shown that the expression of TLR4 (Toll-like receptor 4) and its downstream signaling molecules MyD88 (Myeloid differentiation factor 88), NF-\(\kappa\)B, and TNF-\(\alpha\) in aortic tissue were inhibited after GP intervention (80 and 160 mg/kg for 10 weeks, i.e. ), thus alleviating vascular inflammation [61]. Studies had demonstrated that phytoestrogens, compounds with structural similarities to estradiol, could bind weakly to estrogen receptors and play a major role in the prevention and treatment of AS. Gypenside XVII (GP-17), a novel phytoestrogen, had a similar structure to estradiol, and its anti-atherogenic effect of GP-17 had been verified in vivo and vitro. GP-17 treatment (50 mg/kg) significantly decreased blood lipid levels, increased the expression of antioxidant enzymes, and decreased atherosclerotic lesion size, thus effectively preventing the progression of atherosclerosis in ApoE-/ mice. Oxidized low-density lipoprotein (Ox-LDL) in the pathogenesis of atherosclerosis was an exceptionally important risk factor, which contributed to endothelium apoptosis. GP-17 (50 \(\mu\)g/mL) significantly inhibited Ox-LDL-induced ROS generation and apoptosis in human umbilical vein endothelial cells (HUVECs) by the estrogen receptor alpha (ER\(\alpha\))/PI3K/Akt pathway. Furthermore, GP-17 had been verified as a selective ER\(\alpha\) modulator for atherosclerosis treatment [49]. With the deepened understanding of the pathogenesis of AS, the inhibition of the formation of macrophage foam cells and atherosclerotic plaque had been paid more attention for new drug development. The formation of macrophage foam cells was through scavenger receptor-mediated endocytosis of Ox-LDL. CD36 receptor was the most important scavenger receptor in the macrophage cell membrane to mediate the endocytosis of Ox-LDL. Studies had shown that the expression of the scavenger receptor of CD36 in macrophages was downed by GPS intervention (100 \(\mu\)g/mL), whereby the intake of Ox-LDL in macrophages was reduced [50]. In addition, [PERSON] et al. confirmed the inhibitory effect of gypenoside LVI (GPLVI) on Ox-LDL-induced foam cell formation for the first time.