## 3 AD and PD and Bioactive Rosemary Compounds with Health-Promoting Effects
### Other Bioactive Compounds for Treating NDs  
Carnosol does not appear in as many reports as RA and CA for neuroprotection against PD. One in vitro study in neuronal cells, specifically HT2 cells, had been found. The results showed an increase in ARE activity and GSH synthesis. In the PC12 cell line, there was a stimulation of ERK, JNK, p38, and PI3K/Akt; PI3K/Akt-dependent activation of Nrf2; an increase in HO-1; and a decrease in H\({}_{2}\)O\({}_{2}\) toxicity [14; 40]. Moreover, an older study on rotenone-induced neurotoxicity in SN4741 cells examined the neuroprotective effect of carnosol. The outcome was indeed proved the neuroprotective ability of carnosol, as cell viability was improved through inhibiting caspase-3. Moreover, CS increased the levels of TH, Nurrl, and extracellular signal-regulated kinase 1/2 [11]. In vivo, carnosol had an anti-depressant effect in mice [14]. Another RO compound investigated for its neuroprotective effect is eugenol or 2-methoxy-4-(2-propenyl-phenol). Eugenol was used in a study in PC12 cells examining cell viability and the regulation of DA release, and concluded that the compound may be beneficial against the symptoms of PD, as it can increase the hormone's availability [102]. In an in vivo study, MPTP led to motor impairment in a mouse model, and a decrease in glutathione levels and lipid peroxidation, while treatment with the phenylpropanol reversed these effects. Lastly, eugenol can reduce the possibility of PD development but it cannot cure PD [103]. Another in vivo study analyzed the effect of combining eugenol with levodopa in 6-OHDA-stimulated Wistar rats. The findings showed that the combination of these chemicals decreased the PD-associated symptoms, in contrast to L-dopa alone, and increased GSH synthesis [104]. Luteolin, a flavonoid compound of the herb, was also used in 6-OHDA-treated PC12 cells. Overall, cell pretreatment with luteolin reduced the ROS production induced by 6-OHDA and downregulated the p53, UPR (unfolded protein response), and Nrf2-ARE pathways, making it a potential neuroprotective agent against PD [105]. Also, a luteolin derivative, luteolin-7-O-glycos (LUT-7-G), was given before the MPTP and 1-methyl-4-methylpyridinium (MPP\({}^{+}\)) treatment of SH-SY5Y cells, resulting in an extension of the cells' life. On the one hand, there was an increase in the Bcl-2/Bax ratio, while on the other hand, the cleaved caspase-3 level was reduced. Additionally, there was an increase in estrogen receptor (ER), Erox, and Er\(\beta\) levels, and a boost in the activation of the ERK1/2 (extracellular signal-regulated kinase 1/2)/STAT3 (signal transducer and activation of transcription 3)/c-Fos pathway. In vivo, LUT-7-G pretreatment enhanced bradykinesia and muscle strength while balancing the capacity of the mice treated with MPTP. Lastly, the cells containing TH were protected from injury, TH nerve fibers were found at higher quantities, and MPTP-inducedgliosis in the SN was reduced, making LUT-7-G a potential neuroprotective candidate [106]. Additionally, 1,8-cineole and a-pinene were examined in PC12 cells. Pretreatment with the two terpenes increased cell survival while inhibiting intracellular ROS accumulation and increasing the presence of antioxidant enzymes. The low levels of caspase-3 revealed minimal levels of apoptosis. Eliminating ROS and activating the Nrf2 factor through induction led to another conclusion: the two terpenes possess antioxidant effects and may be protective against diseases associated with oxidative stress, like Parkinson's [107]. Lastly, unsolic acid (UA), another rosemary compound, was used in vivo in rotenone-treated rats, revealing its potential as a neuroprotective agent against PD. Treatment with UA protected TH-positive cells, enhanced cognitive function in the Barnes maze (BMT), and minimized the oxidative stress and inflammation caused by the rotenone infusion.