ORIGINAL PAPER Neuroprotective Effect of Hesperidin on Aluminium Chloride Induced Alzheimer’s Disease in Wistar Rats Arokiasamy Justin Thenmozhi • Tharsius Raja William Raja • Udaiyappan Janakiraman • Thamilarasan Manivasagam Received: 27 October 2014 / Revised: 14 January 2015 / Accepted: 20 January 2015 Ó Springer Science+Business Media New York 2015 Abstract The present study was aimed to evaluate the protective effect of hesperidin (Hes) on aluminium chloride (AlCl 3 ) induced neurobehavioral and pathological changes in Alzheimeric rats. Intraperitonial injection of AlCl 3 (100 mg/kg body weight) for 60 days significantly elevated the levels of aluminium (Al), activity of acetylcholines- terase (AChE) and protein expressions of amyloid precur- sor protein (APP), b amyloid (Ab 1–42 ), b and c secretases as compared to control group in hippocampus and cortex of rat brain. Hes administration orally along with AlCl 3 injection for 60 days, significantly revert the Al concen- tration, AChE activity and Ab synthesis-related molecules in the studied brain regions. Our results showed that alu- minum exposure was significantly reduced the spontaneous locomotor and exploratory activities in open field test and enhanced the learning and memory impairments in morris water maze test. The behavioral impairments caused by aluminum were significantly attenuated by Hes. The his- topathological studies in the hippocampus and cortex of rat brain also supported that Hes (100 mg/kg) markedly reduced the toxicity of AlCl 3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. From these results, it is concluded that hesperidin can reverse memory loss caused by aluminum intoxication through attenuating AChE activity and amyloidogenic pathway. Keywords Alzheimer’s disease Á AlCl 3 Á Hesperidin Á Memory loss Á Ab synthesis Introduction Alzheimer’s disease (AD) is the most common form of dementia, associated with neuropathological and neurobe- havioral changes accompanied by memory and cognitive impairments. It is characterized by excessive production and accumulation of Ab peptide, the pathological product of amyloid precursor protein (APP) by sequential proteo- lytic action of b- and c-secretases [1]. Aluminum (Al) is the third most abundant metal in the earth’s crust and its role in the etiology and pathogenesis of AD has drawn more perceive, due to the well documented animal exper- iments [2] and clinical studies [3]. It is reported that Al is known to accelerate extracellular Ab generation and aggregation [4, 5]. Al acts as a cholinotoxin [6] and cause alterations on the cholinergic activity, a key event in the neurochemistry of AD [7]. Acetylcholinesterase (AChE) inhibitors (donepezil, riv- astigmine, etc.,), NMDA antagonists (Memantine), anti- hyperammonemic drugs (Carveditol), anti inflammatory drugs (rofecoxib) and secretase inhibitors (Memoquin) were shown to have neuroprotective effects with consid- erable side effects and could not be used successfully [8]. Now, the global scenario of therapeutic research is towards herbal or alternate system of medicine. Epidemiological studies showed a link between the consumption of plant- derived foods and a range of health benefits, at least par- tially, to some of the phytochemical constituents including polyphenols [9]. Flavonoids are a broad class of polyphe- nolic compounds that exhibit neuroprotective properties in experimental models of AD, stroke, PD etc., [10] and influence normal cognitive function [11]. Hesperidin (Hes, 3, 5, 7-trihydroxy flavanone-7-rham- noglucoside) is a biologically and pharmacologically active citrus bioflavonoid, abundantly found in sweet orange and A. J. Thenmozhi (&) Á T. R. W. Raja Á U. Janakiraman Á T. Manivasagam Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India e-mail: justinthenmozhi@rediffmail.com 123 Neurochem Res DOI 10.1007/s11064-015-1525-1