Premna odorata extract as a protective agent on neurotoxic effect of aluminum: neurochemical, molecular, and histopathological alterations

Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant, where some reports claimed their anti-inflammatory, cytotoxic, and antituberculosis effects, without investigating its role on the brain. Therefore, forty mature male rats were equally divided into 4 groups; the 1st was kept as control. Rats in groups 2 and 4 were orally given P. odorata extract daily at a dose of 500 mg/kg B.W., while those in groups 3 and 4 were daily administrated aluminum chloride "AlCl₃" (70 mg/kg B.W.). The treatments extended for 30 successive days. At the end of the experimental period, brain samples were collected for biochemical assay of glutathione reductase (GSH), catalase, malondialdehyde (MDA), and acetylcholinesterase activity (AChE). Besides, monoamines (norepinephrine, dopamine, serotonin), amino acids (glutamine, serine, arginine, taurine and gamma-aminobutyric acid (GABA)), neurotransmitters, DNA damage, cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α genes were estimated. Moreover, brain samples were obtained for histopathological investigation. Aluminum toxicity resulted in a decline of GSH concentration, elevation of MDA, and AChE activity. Except for GABA which exhibited a significant decrease, there was a marked increase in the measured amino acid and monoamine neurotransmitters. Also, an increase in mRNA expressions of TNF-α and COX-2 was detected. It was noticed that Premna odorata extract reduced the oxidative stress and counteracted the augmentations in AChE caused by AlCl₃. Marked improvements in most measured neurotransmitters with downregulation of pro-inflammatory gene expression were recorded in P. odorata + AlCl₃ group. Premna odorata restores the altered histopathological feature induced by AlCl₃. In conclusion, the present findings clarify that P. odorata extract could be important in improving and treatment of neurodegenerative disorders as it was able to reduce oxidative stress, DNA damage, biochemical alterations, and histopathological changes in rats exposed to AlCl₃ toxicity.

Keywords: AChE; Aluminum chloride; Gene expression; Monoamine neurotransmitters; Neurotoxicity; Oxidative stress; Premna odorata.