Mal J Med Health Sci 16(SUPP14): 39-43, Dec 2020 39 Malaysian Journal of Medicine and Health Sciences (eISSN 2636-9346) ORIGINAL ARTICLE The Effect of Citrus Peel Extract (Citrus Reticulata) on Hippocampal Histopathological Appearance in Wistar Rats Induced by Trimethyltin Chloride Fini Andriani 1 , Talitha Salsabila 1 , Bilqis Nabilah 1 , Endang Kumaidah 2 , Hardian 2 , Ainun Rahmasari Gumay 2 1 Undergraduate Student, Faculty of Medicine, Diponegoro University, Semarang, 50275 Indonesia 2 Department of Physiology, Faculty of Medicine, Diponegoro University, Semarang, 50275 Indonesia ABSTRACT Introduction: Oxidative stress and chronic inflammation play an important role in neurodegenerative disease. Flavonoids in citrus peel have antioxidant and antiinflammation activity which contribute as neuroprotective agent. The aim of this study is to determine the effect of citrus peel extract (Citrus reticulata) to hippocampal histopathological in Wistar rats were induced by trimethyltin chloride. Methods: 30 male Wistar rats were divided into five groups those were C1, C2, P1, P2 and P3. The C1 group was administered standard diet. The C2 group was injected intraperitoneally by trimethyltin chloride with a single dose (8 mg/kgBW). P1, P2, and P3 groups were injected intraperitoneally by trimethyltin chloride with a single dose (8 mg/kgBW) and administered orally by citrus peel extract after 48 hours injection of trimethyltin chloride with doses 56.25; 112.5; and 225 mg/kgBW/day until 14 th day. On 15 th day, samples were terminated and hippocampal tissues were collected for microscopic preparations. Results: The number of degenerative neurons of hippocampus in C2 (35.80 ± 13.084) was significantly higher than P1 (19.20± 9.230; p=0.049), P2 (15.80 ± 4.919; p=0.013) and P3 (19.60 ± 4.929; p=0.032). There was a significant difference of the number of degenerative neurons of hippocampus between C1 (19.40 ± 7.232) and C2 (35.80 ± 13.084; p=0.040). Conclusion: Administration of citrus peel extract (Citrus reticulata) gave an effect for hippocampal histopathological appearances in Wistar rats induced by trimethyltin chloride. Keywords: Citrus peel extract, Trimethyltin chloride, Neuroprotective agent, Hippocampal histopathological Corresponding Author: Ainun Rahmasari Gumay, M.Sc Email: ainungumay@fk.undip.ac.id Tel: +6281325093344 INTRODUCTION Dementia is neurodegenerative disease that progressively attacks two or more cognitive functions. According to data from World Health Organization (WHO), there were estimated 35.6 million people worldwide living with dementia in 2010 and are expected will increase doubly every 20 years, reaching 65.7 million in 2030 and 115.4 million in 2050 (1). The most common form of dementia is Alzheimer’s Disease (AD), accounting for around 60-70% of cases. The incidence of AD increases with age, it is around 3% at the age of 65-74 years, 19% at the age of 75-84 years and 47% at the age of more than 84 years (2). Neurodegenerative disease is a progressive degeneration process and gradually attacks the nervous system. Oxidative stress and chronic inflammation have big contribution in the process of neurodegenerative diseases. In physiological conditions, the levels of free radicals are maintained and regulated by enzymatic and non-enzymatic antioxidant activities. Excessive levels of reactive oxygen species (ROS) or reactive nitrogen species (RNS) result in an inflammation process in neuron (3). High metabolic activity and low antioxidant defense ability cause neurons in the brain to be more susceptible to oxidative stress, especially in neurons of aging brain.(4) The pathogenesis of Alzheimer’s disease begins with the formation of Aβ deposits in the brain due to the mutation of amyloid precursor proteins (APP). Accumulation of Aβ in the brain results in oxidative damage to neurons (5). Nowadays there is no effective therapy for neurodegenerative diseases, and mostly the marketed drugs are available for symptomatic therapy. Therefore, a lot of study had been done to find natural ingredients which are proposed as neuroprotector agents, one of them is citrus peel (3). Polymethaloxyflavones (PMFs) is the most abundant flavonoid in citrus peel which play a great contribution as an antioxidant and