Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense,
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense, and pCREB/BDNF signaling in the hippocampus and frontal cortex Yong-Hyun Ko1 • Seung-Hwan Kwon1 • Seok-Yong Lee1 • Choon-Gon Jang1
Received: 5 April 2019 / Accepted: 22 June 2019 The Pharmaceutical Society of Korea 2019
Abstract Isoorientin (ISO) is considered one of the most important flavonoids with various pharmacological effects such as antioxidant, anti-inflammatory, and anti-cancer activities. Despite these beneficial activities, the effects of ISO on learning and memory have not been investigated so far. The current study evaluated the memory-enhancing effects of ISO in a scopolamine-treated mouse model by using the Y-maze and passive avoidance tests. The results showed that ISO (5 and 10 mg/kg, p.o.) treatment significantly improved the cognitive impairments caused by scopolamine. Additionally, ISO significantly decreased scopolamine-induced acetylcholinesterase and thiobarbituric acid reactive substance activities in both the hippocampus and frontal cortex of mice. In addition, ISO significantly increased the levels of total superoxide dismutase induced by scopolamine in the hippocampus and frontal cortex. Moreover, Western blot results indicated that ISO reversed the decreases in expression of phosphorylated cAMP response element binding (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus and frontal cortex of scopolamine-treated mice. Thus, our results provide initial evidence that ISO ameliorates scopolamine-induced memory and cognitive impairments partly by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling pathway, thereby exhibiting memory-enhancing activities.
Yong-Hyun Ko and Seung-Hwan Kwon contributed equally to this work. & Choon-Gon Jang [email protected] 1
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
Keywords Isoorientin Cognitive function Cholinergic system Brain-derived neurotrophic factor cAMP response element binding Alzheimer’s disease
Introduction Alzheimer’s disease (AD) is an age-related neurodegenerative disorder with progressive memory loss (Lee et al. 2015). Extensive studies of AD have shown that amyloidbeta accumulation, senile plaques, and aberrant oxidative and inflammatory processes cause cognitive and memory impairments in the central nervous system (Lee et al. 2011; Serrano-Pozo et al. 2011). Furthermore, several studies have demonstrated that brains of patients with AD have a loss of cholinergic neurons and acetylcholine receptors (Mufson et al. 2008). Therefore, restoring cholinergic function in the brain is a therapeutic target for treating or preventing memory-related disorders such as AD. Currently, various acetylcholinesterase inhibitors, such as tacrine and galantamine, have been used to treat AD symptoms (Mehta et al. 2012). However, these drugs can only reduce progres
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