RESUMO
Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1ß), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid ß plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.
RESUMO
Opuntia ficus-indica (L.) Mill. (OFI), also known as Indian fig Opuntia or prickly pear, is a member of the family Cactaceae that produces edible, nutritionally rich sweet fruits. It has been traditionally used to treat several health disorders and is considered to possess various therapeutic properties. In this work, we have characterized 37 secondary metabolites using HPLC-MS/MS, identified the polysaccharide from the fruits and cladodes pulp, and estimated the neuroprotective activity. All tested extracts exhibited substantial antioxidant activities in-vitro and neuroprotective potential in AlCl3 induced Alzheimer's condition. Administration of OFI extracts attenuated AlCl3 induced learning and memory impairment as confirmed from passive avoidance test and counteracted the oxidative stress as manifested from decreasein the elevated MDA level, increased TAC, GSH, SOD and CAT levels. OFI extracts significantly decreased the elevated brain levels of proinflammatory cytokines (NF-κß and TNF-α), increased anti-inflammatory cytokine (IL-10), and monoamine neurotransmitters (NE, DA, 5-HT) as compared to positive control group. The extracts showed a significant decrease in acetylcholinesterase level (AChE) as compared with AlCl3. Furthermore, molecular docking was performed to investigate the ability of the major constituents of OFI extracts to interact with acetylcholinesterase (AChE) and serotonin transporter (SERT). Among the tested extracts, cladodes contain highest phenolic content and exhibited the highest antioxidant, anti-inflammatory and neuroprotective activities, which could be attributed to presence of several polyphenols, which could function as AChE and SERT inhibitors. Opuntia ficus-indica might be promising candidate for treating Alzheimer disease, which makes it a subject for more detailed studies.
