6-Paradol Modulates the Amyloidogenic Pathway and Cognitive Decline in a Streptozotocin Mouse Model of Sporadic Alzheimer’s Disease; In-vivo and Insilico Studies

Document Type : Original Article


1 Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah

2 Pharmacognosy department, Faculty of Pharmacy-Cairo University

3 Department of Pharmacology &Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

4 Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt


There is a great interest in developing new drugs for the prophylaxis and treatment of Alzheimer's disease (AD) from natural and synthetic sources. 6- Paradol is a principal phenolic constituent in plants belonging to the family Zingiberaceae. This compound’s anti-inflammatory, anti-apoptotic, and antioxidant properties suggest that it could be used to treat Alzheimer's disease. In this study, 6- paradol was purified from Aframomum melegueta seeds and tested for the possible effect on the STZ-induced Alzheimer’s disease model in mice at two dose levels (10 and 20 mg/kg). The curative effects of 6- paradol were assessed by measuring the level of amyloid β 42, α, β, and γ -secretases. Furthermore, the enhancement of cognitive abilities in mice following treatment was evaluated using the Y and water maze. Additionally, docking studies were conducted to analyze how effective 6-paradol could be in treating Alzheimer's in humans, by looking at its interaction with human Aβ 42, α, β and γ-secretase active sites. The results demonstrated that 6-paradol improved cognitive and behavioral impairments as well as AD-like pathology in the streptozotocin model in mice. These beneficial effects were accompanied by a reduction in cerebral Aβ 42, β and γ-secretase activities with increasing of α-secretase activity. Moreover, the experiment showed that 6-paradol binds effectively to the examined active sites, implying that further investigation could be conducted to explore its possible benefits for treating Alzheimer's in humans.