## 3 AD and PD and Bioactive Rosemary Compounds with Health-Promoting Effects
### More Neuroprotective Properties of RO and Its Compounds  
Rosmarinic and caffeic acids have also been investigated in mice, and were shown to be neuroprotective against oxidative stress and DNA damage [114]. In male Wistar rats, RA protected the spinal cord from injury, and demonstrated neuroprotection by decreasing the levels of cytokines, such as TNF-a and Nrf2, which are oxidative stress indicators, and other antioxidant enzymes [115]. In another study, including young and aged mice, the outcome indicated that the EO of _R. officinalis_ improves memory in both age groups. Still, its efficacy was more apparent in aged mice [116]. In vivo, studies in humans also support the role of rosemary EOs in short-term image and numerical memory in secondary school students, as well as in the amelioration of cognition and the subjective state in healthy volunteers, with emphasis being given to the link between 1,8-cineole levels and their beneficial effect [117; 118; 119]. All the previous studies utilized inhalation as the administration method. As a noteworthy comment, it is interesting to mention that when comparing rosemary and lavender, it is clear that rosemary is better at ameliorating cognitive performance [117; 119]. Moreover, CA presents potent inhibition of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLP3) inflammasome both in vitroand in vivo. CA downregulates NLRP3 expression by inhibiting NF-\(\kappa\)B, while at the same time, it acts on NLRP9 inflammasome formation and induction by reducing mitochondrial ROS and stopping NLRP3-NIMA-related kinase (NEK7) synergy [120]. CA is a potent blocking agent of the activation of superoxide anion via the xanthine oxidase pathway. It has promising protective abilities towards dopaminergic neuronal cells, protecting them from toxicity by boosting neurotrophic factors and slowing down cell death processes [121]. In another study evaluating the properties of an RO extract and spearmint extract (with the main constituents being CA and RA) on cognition and recall in a SAMP8 mouse model of rapid aging, improved performance was observed in most tests [122]. Camphor was found to have neuroprotective properties against depression. In Wistar albino male rats, depression was induced by ciprofloxacin. The results after treatment with camphor showed an increase in catalase and Nrf activities and a downregulation of NO, malondialdehydedehyde (MDA), TNF-\(\alpha\), and Toll-like receptor 7 (TLR4) serum levels, while there was also a rise in serotonin, DA, GABA (gamma-amino butyric acid), and Rho family GTPase-activating guanosine-5\({}^{\prime}\)-triphosphate (P190-RHO GTP) protein levels, with non-pathogenic neuronal cells in the front cortex of the brain, making camphor a potential neuroprotective compound against major depression [123]. Furthermore, the ability of RA to prevent spinal cord injury (SCI) and promoting nerve repair in an in vivo SCI rat model is shown in Figure 5.  
Figure 5: Pathways affected by RA as a protective agent against SCI while assisting in nerve restoration. RA displays neuroprotective properties, combating oxidative stress and inflammation by stimulating the Nrf/HO-1 signaling pathway and inhibiting the NF-\(\kappa\)B signaling mechanism in SCI rat models.