Abstract
Alzheimer’s disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD (SAD) associated neuropathological changes. The present study was undertaken to explore the neuroprotective effects of the methoxy flavonoid, umuhengerin, in an STZ-induced SAD mouse model as a potential therapy for AD. Mice were injected once with STZ (3 mg/kg, ICV), followed by daily administration of umuhengerin (orally, 30 mg/kg) or the positive control donepezil (orally, 2.5 mg/kg) for 21 days. The pharmacological activity of umuhengerin was assessed through estimation of oxidative stress and inflammatory markers via mouse ELISA kits, Western blot analysis, and brain histopathological examination. Morris water maze test was also conducted to investigate umuhengerin-induced cognitive enhancement. The results showed that umuhengerin attenuated STZ-produced neuroinflammation and oxidative stress with a notable rise in the expression of Nrf2 (nuclear factor erythroid 2-related factor 2). In contrast, it downregulated Keap-1 (Kelch-like ECH associated protein 1), as well as elevated brain contents of GSH (reduced glutathione) and HO-1 (heme oxygenase-1). STZ-injected animals receiving umuhengerin showed marked downregulation of the nuclear factor kappa beta (NF-Kβp65) and noticeable increment in the expression of its inhibitor kappa beta alpha protein (IKβα), as well as prominent reduction in malondialdehyde (MDA), H2O2 (hydrogen peroxide), and TNF-α (tumor-necrosis factor-alpha) contents. Β-secretase protein expression and acetylcholinesterase (AchE) activity were also diminished upon umuhengerin injection in the STZ group, leading to decreased Aβ formation and cognitive improvement, respectively. In conclusion, umuhengerin neuroprotective effects were comparable to the standard drug donepezil; thus, it could be an alternative approach for AD management.
Highlights
Alzheimer’s disease (AD) is characterized by Aβ plaque accumulation and neurofibrillary tangles formation [1]
Psiadia punctulate andand identified based on Umuhengerin(Figure (Figure1)1)was wasisolated isolatedfrom from
As for day, normal animals received umuhengerin showed no significant difference inthe thetest time spent in the target that quadrant in which the platform no significant difference in the time spent in the target quadrant in which the platform was formerly placed, in comparison with control mice
Summary
Alzheimer’s disease (AD) is characterized by Aβ (amyloid-β) plaque accumulation and neurofibrillary tangles formation [1]. Injection of a small dose of streptozotocin (STZ) intracerebroventricularly (ICV) is reported to serve as a reputable mimicker model of SAD, as the injected animals displayed behavioral, neurochemical, and structural changes that accompany human SAD This model is associated with a marked increment in oxidative stress and proinflammatory markers, as well as cholinergic derangement, Aβ accumulation, and cognitive impairment, which are well-known pathological changes linked to SAD [8]. Augmented cognitive abilities via the protection of neurons against oxidative stress, and the inhibition of AChE and β-secretase activities [9]. These are shown to be capable of augmenting vascular blood flow and initiating neurogenesis [10]. Due to flavonoid-associated positive pharmacologic effects, we undertook this study to investigate umuhengerin as a potential candidate for combating STZ-induced neurodegeneration and cognitive decline
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
