Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents 60–70% of all dementia cases. AD is characterized by the formation and accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuronal cell loss. Further accumulation of Aβ in the brain induces oxidative stress, neuroinflammation, and synaptic and memory dysfunction. In this study, we investigated the antioxidant and neuroprotective effects of the natural flavonoid lupeol in the Aβ1–42 mouse model of AD. An Intracerebroventricular injection (i.c.v.) of Aβ (3 µL/5 min/mouse) into the brain of a mouse increased the reactive oxygen species (ROS) levels, neuroinflammation, and memory and cognitive dysfunction. The oral administration of lupeol at a dose of 50 mg/kg for two weeks significantly decreased the oxidative stress, neuroinflammation, and memory impairments. Lupeol decreased the oxidative stress via the activation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) in the brain of adult mice. Moreover, lupeol treatment prevented neuroinflammation by suppressing activated glial cells and inflammatory mediators. Additionally, lupeol treatment significantly decreased the accumulation of Aβ and beta-secretase-1 (BACE-1) expression and enhanced the memory and cognitive function in the Aβ-mouse model of AD. To the best of our knowledge, this is the first study to investigate the anti-oxidative and neuroprotective effects of lupeol against Aβ1–42-induced neurotoxicity. Our findings suggest that lupeol could serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.

Quinpirole-Mediated Regulation of Dopamine D2 Receptors Inhibits Glial Cell-Induced Neuroinflammation in Cortex and Striatum after Brain Injury

“…The western blot analysis was assessed as previously described with minor changes [ 25 , 26 , 27 ]. In brief, an equal volume of 20–30 μg of proteins (extracted from the ipsilateral cortex) was mixed with 2× Sample Buffer (Invitrogen).…”

Herbal Mixture of Carthamus tinctorius L. Seed and Taraxacum coreanum Attenuates Amyloid Beta-Induced Cognitive Dysfunction In Vivo

“…In addition, BACE exerts β-secretase activity in the brain, promoting AD pathology [ 44 ]. Neurodegeneration induced by ICV injection of Aβ 1-42 in mice significantly increased BACE expression [ 49 ]. In addition, BACE cleaves APP and subsequently generates sAPPβ and C99 [ 50 ].…”

Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain

“…Experimental procedures were conducted in accordance with the Animal Ethics Committee (IACUC) of the Division of Applied Life Science, Department of Biology, Gyeongsang National University, Korea (Approval ID: 125). We used male mice in this study because they are resistant to stress, tough ecological conditions, and hormonal alteration [ 23 ].…”

“…with Aβ 1–42 (Aβ 1–42 group), and (3) mice injected with Aβ 1–42 and NAM (via I.P route) NAM + Aβ 1–42 (250 mg/kg for 1 week); dosages of NAM were selected following previously published studies [ 17 ]. The NAM-alone group was not examined in the current study, as no ill effects of NAM have previously been reported in the brain [ 17 , 23 ]. Fresh NAM was prepared on daily basis in a normal saline solution followed by the needed volume of injection, and it was injected into the mice for treatment.…”