## 3 Pharmacological Properties of GP  
### Anti-Cancer Effect  
To date, numerous studies have demonstrated the strong anti-cancer effect of the main components of GP, such as GPS, GPP, and flavonoids (as shown in Table 1). There are several mechanisms of GP's anti-cancer effect, as shown in Figure 4.  
Figure 3: Structures of two cucurbitane-type saponins. Figure 2: Structures of new dammarane-type saponins. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Active Ingredient** & **Model** & **Mechanism** & **Ref. ** \\ \hline \multirow{4}{*}{Gypenoside LI} & \multirow{4}{*}{Melanoma cells (A375 and SK-MEL-28)} & Induced intrinsic apoptosis along with S phase arrest, decreased the levels of CDK2, P-CDK2, Bcl-2, and FLIP, increased the levels of caspase 9, PARP cleavage, and BID death agonist, and increased the level of tumor suppressor miR-128-3p. \\ \hline \multirow{4}{*}{Gypenoside LI} & \multirow{4}{*}{Human breast cancer cells (MDA-MB-231 and MCF-7)} & Induced intrinsic apoptosis along with S phase arrest, decreased the levels of CDK2, P-CDK2, Bcl-2, and FLIP, increased the levels of caspase 9, PARP cleavage, and BID death agonist, and increased the level of tumor suppressor miR-128-3p. \\ \hline \multirow{4}{*}{Gypenoside LI} & \multirow{4}{*}{Human breast cancer cells (MDA-MB-231 and MCF-7)} & Inhibited the proliferation by decreasing the expression of ERCC6L, down-regulated the expression of MMP2 and MMP9, suppressed the migration ability of breast cancer cells, induced cell apoptosis, increased cytochrome c release from mitochondria into the cytoplasm, increased levels of Bax, decreased levels of PARP-1 and Bcl-2, induced cell cycle arrest in G0/G1 phase via down-regulating E2F1 and decreasing CDK2, CDK4, and cyclin D1. \\ \hline \multirow{4}{*}{Gypenoside L} & \multirow{4}{*}{Human hepatic cancer HepG2 cells and esophagus cancer (p21 and p27) and their upstream regulators, activated p38 and ERK MAPK pathways and NF-kB pathway to induce senescence.} \\ \hline \multirow{4}{*}{Gypenoside L} & \multirow{4}{*}{Human esophageal cancer cells (ECA-109 and TE-1)} & Induced cell death, which was associated with lysosomal swelling and autophagic flux inhibition, increased the levels of ROS, triggered protein ubiquitination and ER stress response, leading to Ca2+ release from ER IP3R-operated stores and finally cell death. \\ \hline \multirow{4}{*}{Gypenoside L} & \multirow{4}{*}{Human hepatocellular carcinoma cells} & Increased the intracellular ROS levels, which triggered protein ubiquitination and unfolded protein response, resulting in Ca2+ release from ER IP3R-operated stores and finally cytoplasmic vaccination and cell death. \\ \hline \multirow{4}{*}{Gypenoside L} & \multirow{4}{*}{Human lung cancer A549 cells} & Inhibited A549 cell migration from the upper to the lower chamber through the membrane, decreased the expression of MMP2 and MMP9, gynenoside L down-regulated the expression of CDK2 and CDK4 proteins rather than CDK1 protein, while gynenoside LI suppressed the expression of CDK1 protein rather than CDK2 and CDK4 proteins. Gypenoside L induced G0/G1 arrest and gynenoside LI induced G2/M arrest in A549 cells; induced A549 cell apoptosis through extrinsic pathway and intrinsic pathway, boosted the production of ROS, led to more cytochrome c release from mitochondria into cytoplasm and less expression of proaspase 8. \\ \hline \multirow{4}{*}{GPS} & \multirow{4}{*}{Human lung cancer A549 cells} & Increased p16, p21, p27, and p53 proteins and induced G0/G1 arrest; induced apoptosis by up-regulating Bax, caspase-3, and caspase-9 and down-regulating Bcl-2 levels. \\ \cline{1-1}  & & Induced DNA fragmentation and cell apoptosis, induced ROS and Ca2+ production, decreased the expression of Bcl-2 and Bcl-xl but increased the expression of Bax, increased the levels of p53 and promoted the release of cytochrome c and the activation of caspase-3, induced G0/G1 arrest, decreased the levels of cyclin D3, cyclin E, CDK4, CDK6 and CDK2, increased the levels of p15, p16, p21, p27, and p53.