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

• Published in: Biomedicines Vol. 8; no. 10; p. 380
• Main Authors: Ahmad, Riaz, Khan, Amjad, Lee, Hyeon Jin, Ur Rehman, Inayat, Khan, Ibrahim, Alam, Sayed Ibrar, Kim, Myeong Ok
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 26-09-2020; MDPI
• Subjects: Alzheimer's disease; Antioxidants; Behavior; Brain; Cognitive ability; cognitive dysfunction; Dementia disorders; Fruits; GA-binding protein; Glial cells; Heme; Heme oxygenase (decyclizing); Inflammation; Membranes; Memory; Natural products; Neurodegeneration; Neurodegenerative diseases; Neurofibrillary tangles; neuroinflammation; Neuronal-glial interactions; Neuroprotection; Neurotoxicity; Oral administration; Oxidative stress; Oxygenase; Pathophysiology; Peptides; Plants; Proteins; Reactive oxygen species; reactive oxygen species (ROS); Secretase; Senile plaques; β-Site APP-cleaving enzyme 1; β-Site APP-cleaving enzymes; United States > US; South Korea
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines8100380

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 triterpenoid 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.