Lavandula angustifolia Effects on Rat Models of Alzheimer's Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics

Abstract

Background: Alzheimer's Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aβ-induced rat Alzheimer's models was investigated through nuclear magnetic resonance spectrometry.

Methods: For the establishment of rat Alzheimer's models, 10 μg of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 MHz 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment.

Results: Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism.

Conclusion: As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed.

Keywords: Alzheimer disease; Lavandula; Metabolomics; Serum.

Figure 1.

3D scatter scores plots for A) PCA and B) PLS-DA models for the comparison of Alzheimer rats versus control group. As can be seen, PLS-DA model could obviously discriminate Alzheimer and control groups. Part C presents the Y observed versus Y predicted and the resulting ROC curve with AUC of 1 after 7-fold cross-validation of the PLS-DA model which confirms the model has well separated the groups.

Figure 2.

3D scatter scores plots for A) PCA and B) PLS-DA models for the comparison of lavender treated rats versus Alzheimer group. Part C, shows the Yobserved versus Ypredicted and the resulting ROC curve with AUC of 1 after 7-fold cross-validation of the PLS-DA model. The groups are well separated by the model.

Figure 3.

10 biomarkers levels were reversed nearly to control values after treatment with lavender extract. The Y-axis represents the relativepeak intensities in NMR spectra (*p<0.05, **p<0.01, ***p<0.001).