## 3 Trepenoids iRIn Human Health
### Neuoprotective Effects of Terpenoids
& [138] \\ \hline \multirow{6}{*}{Methyl lucidone} & HT-22 cell line & Neuoprotective effects on glutamate-induced oxidative stress in HT-22 cells via Nrf-2/HO-1 signaling. & [139] \\ \cline{2-3}  & Limonene & Maternal separation mice & Antidepressant-like effects due to the reduction of nitrite levels in the hippocampus. & [140] \\ \hline \multirow{6}{*}{Lycopene} & Primary mouse neurons & Protected against T-BHP-induced neuronal oxidative damage and apoptosis via activation of the PI3K/Akt pathway. & [141] \\ \cline{2-3}  & Platycodin D & Primary cortical neurons & Protected cortical neurons against oxygen–glucose deprivation/reperfusion in neonatal hypoxic-ischemic encephalopathy. & [142] \\ \cline{2-3}  & & Glutamate-induced cytotoxicity cell model/protects hippocampal neurons against glutamate-induced cytotoxicity. & [143] \\ \cline{2-3}  & Rat adrenal pheochromocytoma cells (PC12) and primary rat cortical neurons & Inhibited neuronal apoptosis induced by oxygen–glucose deprivation and reoxygenation through the PI3K/Akt pathway. & [144] \\ \hline \multirow{6}{*}{Ginsenosides} & Oxygen–glucose deprived (OGD) & Neuoprotective effect of panax notoginseng & \\ \cline{2-3}  & SH-SY5Y cells & saponins by activating the EGFR/PI3K/Akt pathway. & [145] \\ \cline{2-3}  & Mouse model & Protective effects of notoginsenoside R1 via regulation of the PI3K-Akt-mTOR/JNK pathway in neonatal cerebral hypoxic-ischemic brain injury. & [146] \\ \hline \multirow{2}{*}{\(\alpha\)-Pinene} & Focal cerebral I/R in rats & Neuoprotective effect during ischemic stroke by attenuating neuroinflammation/ELISA. & [147] \\ \cline{2-3}  
Although several studies have investigated the bioavailability and blood-brain barrier (BBB) permeability of terpenoid compounds, there are still many challenges inherent in using terpenoids to prevent/treat neurodegenerative diseases. Despite evidence of the neuroprotective potential of terpenoids, the scarcity of clinical evidence and research studies on the application of terpenoids as a treatment for neurodegenerative diseases poses a significant challenge. [PERSON] et al. [PERSON] et al. (2018) evaluated the linalool potential neuroprotective effect in ACR-induced neurotoxicity in Wistar rats using advanced analytical techniques. They concluded that linalool exhibited protective effects against ACR-induced neurotoxicity in Wistar rats through the elevation of GSH contents and the reduction of lipid peroxidation in the cerebral cortex [PERSON] et al. (2018). [PERSON] et al. (2019) examined the effects of two key terpen, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, reporting that linalool and pinene influence multiple neurotransmitter, inflammatory, and neurotrophic signals, as well as behavior, demonstrating psychoactivity (albeit non-intoxicating) [PERSON] et al. (2018) In addition, [PERSON] et al. (2019) reported the in vitro neuroprotective potential of terpen from industrial orange juice by-products through multiple in vitro assays, including a parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB) [PERSON] et al. (2019). Further investigation is necessary to determine the efficacy and safety of terpenoids for treating these conditions [PERSON] et al. (2018). For instance, it is necessary to overcome the low bioavailability and ability to cross the BBB, which limits the effectiveness of terpenoids in the treatment of neurodegenerative diseases [PERSON] et al. (2018); [PERSON] et al. (2018), as well as the lack of studies standardizing dosage and formulation, making it difficult to determine the appropriate dose for patients [PERSON] et al. (2018). Moreover, the mechanisms of action of terpenoids are complex and not fully understood, jeopardizing target identification for treatment [PERSON] et al. (2018) and the identification of potential drug interactions and side effects [PERSON] et al. (2018).