Although cardiovascular diseases, diabetes and cancers still have their high prevalence, life expectancy in the 21st century is increasing resulting in an increase in age-related diseases, such as neurodegenerative diseases such as Parkinson’s and Alzheimer’s dementia . One way to simulate the aging of the body in the laboratory, including the brain, is to administer experimental animals a diet rich in galactose (D-Gal), a simple sugar analogous to glucose. It has been demonstrated that the administration of D-galactose induces cognitive deterioration and aging in rodent models, visible by the expression of specific cellular markers. Geraniol (GEN) belongs to the isoprenoid monoterpenes and reduces inflammation by modifying important signaling and cytokine pathways, and therefore its use as a medicine for the treatment of inflammation-related disorders is plausible.
A joint investigation by researchers from the Universities of Kuwait, Saveetha and Alexandria studied how GEN would be able to antagonize the “senescent” effects of galactose. The study was conducted using six groups of mice (6 mice per group). The first group received normal saline, then D-Gal (150 mg/wt) dissolved in normal saline (0.9%, w/v) was administered orally to the second group for 9 weeks. In group III, from the second week to the tenth week, mice were treated orally (without anesthesia) with D-Gal (150 mg/kg body weight) and GEN twice a week (40 mg/kg body weight). body) four hours later. Group IV mice were treated with GEN from the second week until the end of the experiment. For the comparison between young and old mice, 4-month-old (Group V) and 16-month-old control mice (Group VI) were used.
GEN administration induced a significant increase in spatial learning and memory with spontaneously altered behavior. The enhancement of antioxidant and anti-inflammatory effects and the activation of the cellular PI3K/Akt pathway were the mechanisms that mediated this effect. The PI3K/Akt kinase signal is used by cells for various purposes, such as inducing proliferation, cellular protection from external toxins, oxidative stress and as a protector of cell death (apoptosis). At the brain level it serves neurons to protect themselves from oxidative stress; it is also widely used by nerve stem cells for their regeneration, a process that is compromised in some brain areas (such as the hippocampus) responsible for memory and various cognitive phenomena that decline with aging. Furthermore, GEN treatment upregulated the transcription factor Nrf2 to reduce oxidative stress and apoptosis.
Research published last year confirmed that oral administration of GEN improved passive avoidance memory deficit, improved hippocampal LTP impairment, and reduced the accumulation of amyloid-beta (Aβ) plaques. in rats infused with Aβ. This suggests that this compound mitigates memory impairment by improving hippocampal synaptic function and inhibition of Aβ plaque formation. A complex biochemical-genetic analysis published by an independent group two years ago found that geraniol has a few dozen potential targets inside cells, although five were highlighted as the most likely: CHMR3, PRKCA, PRKCD, JAK1 and JAK2. The first is the M3 cholinergic receptor also present in the brain, the other four are cellular protein kinases that mediate signals downstream of hormone receptors (PRKCA, PRKCD) and growth factors (JAK1, JAK2).
Geraniol is therefore neuroprotective because it is able to stimulate the function of these proteins, protecting the vitality of neurons, defending them from oxidative stress and generating intracellular signals similar to those of important neurotrophic molecules. Its high bioavailability comes from possessing a hydrophobic structure that quickly passes the blood-brain barrier. Furthermore, being a natural molecule present in many aromatic essential oils, its biological safety is known and highly controlled. Consequently, its use could very easily be applied to the prevention or management of age-related cognitive decline or in cases of overt senile dementia.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Rajendran P et al. Aging. 2024 Mar; 16(6):5000-5026.
Bagheri S et al. Eur J Pharmacol. 2023; 951:175714.
Liu Y, Zhou S et al. Eur J Med Res. 2022; 27(1):93.