Abstract
Lupeol, a natural active constituent of Betula alnoides (BA), is well known for its anti-inflammatory, anti-oxidant and neuroprotective activities. In present study the therapeutic potential of lupeol was investigated against amyloid beta (Aβ (1-42)) induced cognitive deficit, neurochemical and biochemical abnormalities in rats. Lupeol was isolated from the BA and its structure was confirmed through nuclear magnetic resonance spectra. Aβ (1-42) (4 μg/4 μL) intracerebroventrically (icv) was administered to rats for the induction of Alzheimer's disease (AD). Lupeol treatment (25 mg/kg/day, 50 mg/kg/day and 100 mg/kg/day per orally) was started one week after Aβ (1-42) infusion up to the 21st days. Morris water maze from day 16 to 21 and object recognition tasks on day 14 and 15 were performed for memory assessment. On 22nd day, animals were sacrificed and hippocampi were isolated for analysis of biochemical (acetylcholinesterase, lipid hydroperoxide, glutathione and nitrite) and neuro-inflammatory (tumor necrosis factor -α, interleukin (IL)-1β, and IL-6) parameters. In the present study Aβ (1-42) infusion was significantly impaired behavioral memory, increased oxidative stress, decreased antioxidant enzyme and increased pro-inflammatory markers. Treatment of lupeol significantly restored Aβ (1-42) induced behavioral and biochemical abnormalities in rats brain. The findings of the present study suggest that lupeol act through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders of AD.
Highlights
Alzheimer's disease (AD) is the most common form of dementia characterized by extracellular deposits of amyloid beta (Aβ (1-42)), intracellular neuro-fibrillary tau tangle, oxidative stress and decline in cognitive functions [1,2,3]
The Fourier transform infrared spectroscopy (FTIR) spectra gave information about the functional groups or chemical entities present in lupeol which was found in accordance with the literature data of lupeol [33]
Further 1H Nuclear magnetic resonance (NMR) spectrum of the compound revealed the presence of seven tertiary methyl protons, a sextet of one proton at δ 2.17 and presence of olefinic protons at (H-29a and b) which is characteristic of lupeol [34]
Summary
Alzheimer's disease (AD) is the most common form of dementia characterized by extracellular deposits of amyloid beta (Aβ (1-42)), intracellular neuro-fibrillary tau tangle, oxidative stress and decline in cognitive functions [1,2,3]. A variety of medicinal plants such as Betula alnoides, Vernonanthura ferruginea and Zanthoxylum rhoifolium have been reported to contain lupeol as an active constituent [13,14,15]. Lupeol has been reported to have various pharmacological activities including acetylcholinesterase (AChE). It has been reported to be effective in various pathologies and recently its neuroprotective effect has been studied [19,20]. The present work was carried out to investigate the neuroprotective potential of lupeol against ICV-Aβ(1-42) induced cognitive impairment, neurotransmitters deficits, neuroinflammation and oxidative-nitrosative stress in rats
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