Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment

Abstract

Alzheimer's disease (AD) is acknowledged as the main causative factor of dementia that affects millions of people around the world and is increasing at increasing pace. Okadaic acid (OA) is a toxic compound with ability to inhibit protein phosphatases and to induce tau protein hyperphosphorylation and Alzheimer's-like phenotype. Kolaviron (KV) is a bioflavonoid derived from Garcinia kola seeds with anti-antioxidative and anti-inflammation properties. The main goal of this study was to assess whether kolaviron can exert neuroprotective effect against okadaic acid-induced cognitive deficit. Rats had an intracerebroventricular (ICV) injection of OA and pretreated with KV at 50 or 100 mg/kg and examined for cognition besides histological and biochemical factors. OA group treated with KV at 100 mg/kg had less memory deficit in passive avoidance and novel object discrimination (NOD) tasks besides lower hippocampal levels of caspases 1 and 3, tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) as inflammatory factors, reactive oxygen species (ROS), protein carbonyl, malondialdehyde (MDA), and phosphorylated tau (p-tau) and higher level of acetylcholinesterase (AChE) activity, mitochondrial integrity index, superoxide dismutase (SOD), and glutathione (GSH). Moreover, KV pretreatment at 100 mg/kg attenuated hippocampal CA1 neuronal loss and glial fibrillary acidic protein (GFAP) reactivity as a factor of astrogliosis. In summary, KV was able to attenuate cognitive fall subsequent to ICV OA which is partly mediated through its neuroprotective potential linked to mitigation of tau hyperphosphorylation, apoptosis, pyroptosis, neuroinflammation, and oxidative stress and also improvement of mitochondrial health.

Keywords: Alzheimer's disease; Apoptosis; Cognition; Inflammation; Kolaviron; Oxidative stress; Pyroptosis.

Fig. 1

Experimental design of the study. KV (50 and 100 mg/kg) was injected for 2 weeks. To induce memory impairment, OA was I.C.V. microinjected at 200 ng/kg. Behavioral assessment was done at 4th week and finally biochemical and histochemical assessments were conducted.

Fig. 2

Findings for performance in Y-maze (A), novel object recognition (B), and shuttle box (C) tests. * for p < 0.05, ** for p < 0.01 and *** for p < 0.001 compared to the sham group. # for p < 0.05 and ## for p < 0.01 versus OA group.

Fig. 3

Hippocampal level of BACE 1 (A) and AChE activity (B). These factors were evaluated three weeks after OA injection. * for p < 0.05 and ** for p < 0.01 (versus the sham); # for p < 0.05 (versus the OA group).

Fig. 4

Hippocampal level of mitochondrial membrane potential (MMP). * for p < 0.05 and *** for p < 0.001 (relative to the sham), # for p < 0.05 (versus the OA group).

Fig. 5

Density of CA1 pyramidal neurons (A) and immunoreactivity for glial fibrillar acidic protein (GFAP). * for p < 0.05, ** for p < 0.01 and *** for p < 0.001 versus the sham group; # for p < 0.05 and ## for p < 0.01 versus the OA group.