## 3 Pharmacological Properties of GP
### Effects on Ischemia-Reverfusion(I/R) Injury  
Tissue ischemia-reperfusion (I/R) injury is the damage caused by excessive free radical attacks on cells in tissues after blood flow recovery on the basis of ischemia. Numerous evidence had confirmed that the saponins and flavonoids in GP exhibited the improvement effect on tissue I/R injury, including renal, hepatic, and myocardial I/R injury (as shown in Table 4). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Active Composition** & **Models** & **Dosage** & **Activity/Mechanism** & **Ref.** \\ \hline \multirow{8}{*}{GPS} & Oxygen-glucose deprivation-reoxygenation (OGD/R) H9c2 cell model & 5, 10, 20 \(\upmu\)M, pretreatment prior to ischemia & Enhanced the cell viability, inhibited the translocation of NF-kB subunit p65 into nuclei, inhibited NF-kB activation by suppressing the MAPK signaling transduction pathway. \\ \cline{2-3}  & Myocardial I/R rat model & 50, 100, 200 mg/kg, pretreatment prior to ischemia, p.o. & \begin{tabular}{c} Enhanced the cell viability, inhibited the translocation of NF-kB subunit p65 into nuclei, inhibited NF-kB activation by suppressing the MAPK signaling transduction pathway. \\ \end{tabular} \\ \cline{2-3}  & OGD/R H9c2 cell model & \begin{tabular}{c} 5, 10, 20 \(\upmu\)M, pretreatment prior to ischemia \\ \end{tabular} & \begin{tabular}{c} Alleviated the impairments on the cardiac function and structure, suppressed the activation of NF-kB via inhibition of phosphorylation of NF-kB \(\upalpha\) (lk8\(\upalpha\)), ERK, JNK, and p38. \\ \end{tabular} \\ \cline{2-3}  & \begin{tabular}{c} OGD/R H9c2 cell model \\ \end{tabular} & \begin{tabular}{c} 5, 10, 20 \(\upmu\)M, pretreatment prior to ischemia \\ \end{tabular} & \begin{tabular}{c} Protected cell viability, reduced ROS production and oxidative stress, and preserved mitochondrial function. \\ \end{tabular} \\ \cline{2-3}  & \begin{tabular}{c} 5, 100, 200 mg/kg, \\ Myocardial I/R rat model \\ \end{tabular} & \begin{tabular}{c} Attenuated infarct size, alleviated I/R-induced pathological changes in the myocardium, and preserved left ventricular function; reduced oxidative stress, preserved mitochondrial function in the cardiomyocytes, maintained mitochondrial membrane integrity, and inhibited the release of cytochrome c from the mitochondria to the cytosol. \\ \end{tabular} \\ \hline \multirow{2}{*}{Gypenoside A} & OGD/R H9c2 cell model & 10, 20 \(\upmu\)M, pretreatment prior to ischemia & Increases cell viability and inhibits apoptosis, exerted its protective effect on H9c2 cells by inhibiting the expression of miR-143-3p via the activation of AMPK. \\ \cline{2-3}  & OGD/R H9c2 cell model & 10, 20 \(\upmu\)M, pretreatment prior to ischemia & \begin{tabular}{c} Exerted protective effect by inhibiting the ER stress-induced apoptosis via inhibition of CHOP pathway and activation of PI3K/Akt pathway. \\ \end{tabular} \\ \cline{2-3}  & Myocardial I/R rat model & \
\begin{tabular}{c} 50, 100, 200 mg/kg, \\ pretreatment prior to ischemia, p.o. \\ \end{tabular} &
\begin{tabular}{c} Chromoved pathway and activation of PI3K/Akt pathway. \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Effects on ischemia–reperfusion(I/R) injury. It had been demonstrated that the generation of I/R injuries is closely associated with inflammation, oxidative damage, and cell apoptosis. Studies in vitro and in vivo had shown that the effect of GPS on I/R-induced injury was mainly attributed to its anti-inflammation, anti-oxidative, and anti-apoptotic activity. An oral treatment with 50 mg/kg GP 1 h prior to ischemia effectively attenuated the I/R-induced increase in the levels of hepatic lipid peroxidation and serum alanine aminotransferase and suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl-2 [102]. [PERSON] et al. [101] evaluated the protective effect against I/R-renal injury and its underlying molecular mechanisms.