## 3 Trepenoids iRIn Human Health
### Neuoprotective Effects of Terpenoids
The PI3K/Akt signaling pathway is an intracellular signal transduction pathway that promotes survival and growth in response to extracellular signals. For this reason, this pathway should be highly regulated by multiple mechanisms involving crosstalk with other signaling pathways. Therefore, it is important to note that several terpenoids are associated with PI3K/Akt signaling regulation, showing their high potential in the prevention of neurodegeneration (Table 4). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Terpenoid** & **Assay** & **Reported Activities** & **Ref.** \\ \hline \multirow{4}{*}{Artesunate} & C57 BL/6 mice (newborn) and primary neural stem/progenitor cells (NSFCs) & Ameliorated the insufficient endogenous neural stem/progenitor cell (NSFC) proliferation caused by ischemia. By stimulating the PI3K/Akt signaling pathway, ART could increase the phosphorylation level of FOXO-3a, downregulate p27 kip1, and inhibit the transcription of FOXO-3a. & [124] \\  & Neuroundally differentiated PC12 cells & Protection against A\(\beta\)25-35-induced apoptosis and tau hyperphosphorylation by regulating PI3K/Akt/GSK-3\(\beta\) signaling. & [125] \\ \hline \multirow{4}{*}{Asiaticoside} & Streptozotocin (STZ)-induced diabetic cognitive deficit rat model & Ameliorated cerebral oxidative stress, inflammation, and apoptosis. & [126] \\ \cline{2-4}  & Streptozotocin-induced hyperglycemia mice & Antioxidant and neuroprotective effects on mouse models of depression, improving their depressive behavior by upregulating the PI3K/Akt/Nrf2/HO-1 signaling pathway. & [127] \\ \cline{2-4}  & Catalyol & Catalyol activated the PI3K/Akt/mTOR pathway, decreasing the expression of miR-124 and increasing the expression of downstream protein S6, thus enhancing in vivo axon growth and neuronal survival in stroke models. & [128] \\ \hline \multirow{2}{*}{Celastrol} & Cacute spinal cord injury rats & Inhibited microglial pyrotosis and attenuated inflammatory reactions. & [129] \\ \cline{2-4}  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Illustrative examples of terpenoid eliciting neuroprotective activities. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Terpenoid** & **Assay** & **Reported Activities** & **Ref. ** \\ \hline \multirow{6}{*}{Geniposide} & Epileptic rats model & Activated Akt, followed by increased PI3K and GSK-3\(\beta\) expression, thus improving pathological symptoms. & [130] \\ \cline{2-3}  & Hippocampal neurons & Inhibited apoptosis, resulting in antidepressant properties in the brain. & [131] \\ \cline{2-3}  & Chronic constriction injury model & Inhibited the EGFR/PI3K/Akt signaling pathway, thereby alleviating pain symptoms in the sciatic nerve. & [132] \\ \hline \multirow{6}{*}{Bilobalide and ginkgolides} & Rat model of middle cerebral artery occlusion & Supported neuronal cell survival in patients suffering from ischemic stroke. & [133] \\ \cline{2-3}  & Rat model of middle cerebral artery occlusion & Bilobalide derivatives (diAc-iso and diBrBr-iso) performed better than the original compound (proliferating cell activity, neuroprotective effects against A\(\beta\) (1–40) peptides, and neurite outgrowth effects). & [134] \\ \hline \multirow{6}{*}{Ginkgolide B} & Rats cerebral I/R damage model & Activation of Nrf2 and CREB through PI3K/Akt signaling. & [135] \\ \cline{2-3}  & Rat model of middle cerebral artery occlusion (MCAO) and OGD/R cell model & Antioxidant effects against cerebral ischemia injury by activating the Akt/Nrf2 pathway. & [136] \\ \hline \multirow{6}{*}{Ginkgolide K} & Primary cortical astrocytes from newborn mice exposed to oxygen–glucose deprivation & Superior therapeutic potential to ginkgolide B; easier to upregulate PI3K and p-Akt expression, affecting downstream pathways, thereby contributing to anti-inflammatory and antioxidant effects. & [137] \\ \cline{2-3}  & Echinocyst acid & Collagen-induced intracerebral haemorrhage mice & Neuoprotective effect via the PI3K/Akt pathway.