Lupeol Isolated from Betula alnoides Ameliorates Amyloid Beta Induced Neuronal Damage via Targeting Various Pathological Events and Alteration in Neurotransmitter Levels in Rat’s Brain

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 21 st days. Morris water maze from day 16 to 21 and object recognition tasks on day 14 and 15 were performed for memory assessment. On 22 nd 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.

BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

“…82 Moreover, other studies indicated that lupeol have neuroprotective property. 84 It has also been reported that lupeol inhibits BACE1 with an IC 50 value of 5.12 μM. 82 In another study conducted by Zhu et al, 85 a library of marine natural products with diverse molecular scaffolds were studied and the results showed anti-AD effects with two steroidal extracts isolated from the U. unicinctus.…”

“…Theoretical calculations of the PK values have shown that lupeol could cross the BBB more efficiently than ursolic acid . Moreover, other studies indicated that lupeol have neuroprotective property . It has also been reported that lupeol inhibits BACE1 with an IC 50 value of 5.12 μM …”

Cerebral Cortex and Hippocampal Protection Mediated by Callistemon viminalis in Aluminium Chloride Induced Alzheimer’s Disease

“…The R f value obtained from TLC was compared with the reported Rf value of the chemical constituent The chemical constituent confirmed by TLC was β-sitosterol, 26 Lupeol, 27 Betulinic acid, 28 Ursolic acid 29 that individually acts on the various pathways of the AD. In our study, chronic administration of aluminium chloride for 42 days caused significant increase in oxidative stress, abnormal biochemical alterations and histological changes in brain which were assessed by estimating behavioral and biochemical parameters.…”

Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1

“…Finally, all molecular simulation studies suggested that the lupeol is potent enough to inhibit BACE1, and this result is also supported by the findings from the recent report of Koirala et al [48], where lupeol also inhibited BACE1 with IC 50 values of 5.12 µmol/L and also exhibiting a very potent inhibition with low inhibition constant (Ki) value of 1.43 mmol/L, demonstrating the greater binding affinity. In addition, lupeol was illustrated to protect mouse hippocampal cell lines HT-22 against glutamate toxicity [49], and also suggested to potential as a neuroprotective agent in neurodegenerative diseases [49,50].…”