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.