Behavioural Brain Research 312 (2016) 20–29 Contents lists available at ScienceDirect Behavioural Brain Research jou rn al hom epage: www.elsevier.com/locate/bbr Research report Beneficial effects of cornel iridoid glycoside on behavioral impairment and senescence status in SAMP8 mice at different ages Denglei Ma, Yanqiu Zhu, Yanzheng Li, Cuicui Yang, Li Zhang, Yali Li, Lin Li ∗ , Lan Zhang ∗ Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China h i g h l i g h t s • CIG could not only treat early AD but also possess beneficial effects on moderate to severe AD. • CIG has the potential effect to ameliorate the daily living qualities and the lifespan of AD patients. • The pharmacological mechanism of CIG related to anti-hyperphosphorylation of tau in SAMP8 mice, which benefits to AD treatment. a r t i c l e i n f o Article history: Received 17 February 2016 Received in revised form 1 June 2016 Accepted 5 June 2016 Available online 6 June 2016 Keywords: Cornel iridoid glycoside Aging SAMP8 Behavior Tau phosphorylation Alzheimer’s disease a b s t r a c t The aim of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on behavioral changes and senescent status in senescence-accelerated mouse-prone 8 (SAMP8) mice at different ages (6, 10, and 14 months old). The learning and memory ability, the motor function and the aging condi- tions of SAMP8 mice were evaluated after CIG treatment in this study. Results showed that intragastrical administration of CIG (100 and 200 mg/kg) for two months obviously improved the impaired cognitive ability of SAMP8 mice at the age of 6 months and 10 months, respectively. The treatment with CIG sig- nificantly increased the motor function of SAMP8 mice at 10 months and 14 months of age, respectively. CIG also evidently decreased the high grading score of senescence and increased the low surviving rate of SAMP8 mice at the age of 14 months. In addition, CIG treatment inhibited tau hyperphosphorylation in the hippocampus and striatum of SAMP8 mice at different ages. Together, these results indicate that CIG represent a potentially useful treatment for ameliorating the impaired cognitive ability, the motor dys- function, aging conditions and hyperphosphorylation of tau in aging and age-related neurodegenerative diseases, such as Alzheimer’s disease. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Aging is associated with the deterioration of memory and motor abilities and with an increased incidence of neurodegenerative disorders, such as Alzheimer’s disease (AD) [1]. Senescence- accelerated mouse (SAM) is a murine model of accelerated aging, spontaneously developed from breeding pairs of the AKR/J series at Kyoto University [2]. Among the stains, senescence-accelerated mouse-resistant 1 (SAMR1) serves as a control exhibiting normal aging phenotype [3], while senescence-accelerated mouse-prone 8 (SAMP8) is one of the strains and widely used as aging-related neurodegeneration animal model [4]. SAMP8 displays irreversible ∗ Corresponding authors at: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China. E-mail addresses: linlixw@126.com (L. Li), lanizhg@126.com (L. Zhang). advancing senescence and share similar characteristics with aged humans and AD patients, such as a shortened lifespan, obvious age- related deteriorative cognition [5–7], physical impairments [7,8], hyperphosphorylation of tau [9], and various pathological features of age-associated neurodegeneration, [4,10,11]. Cornel iridoid glycoside (CIG) is the active ingredient extracted from Cornus officinalis Sieb. et Zucc, a traditional Chinese herb widely used for treatment of dementia and other age-related diseases in China [12]. The main components of CIG are morroniside and loganin. According to a pharmacokinetic study conducted by Chen, et al. [13], both morroniside and loganin are absorbed into blood after intragastrical administration. The HPLC study of tissue dis- tribution in rats has shown that both morroniside and loganin cross the blood-brain barrier [14,15]. In our previous studies, we found that CIG inhibited inflammation and apoptosis in the brain of rats with focal cerebral ischemia [16], promoted neurogenesis and angiogenesis and improved neurological function after stroke http://dx.doi.org/10.1016/j.bbr.2016.06.008 0166-4328/© 2016 Elsevier B.V. All rights reserved.