Niger. J. Physiol. Sci. 37 (December 2022): 207 – 214 www.njps.physiologicalsociety.com Full length Research Article Hippocampus and Prefrontal Cortex Following the Use of Anti- Retroviral Therapy in Adult Wistar Rats: Therapeutic Role of Epigallocatechin Gallate Ogedengbe O.O. 1,2,5 , Saliu H. 2 , Fafure A.A. 2 , Akintayo C.O. 3 , Adekeye A.O. 2 , Ajiboye B.O. 4 , Azu O.O. 5,6 1 Department of Anatomy, Faculty of Basic Medical Sciences, Federal University, Oye-Ekiti, Nigeria 2 Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Nigeria 3 Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Nigeria 4 Department of Biochemistry, Faculty of Science, Federal University Oye-Ekiti, Oye-Ekiti, Nigeria 5 Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, University of KwaZulu- Natal, Durban, South Africa. 6 Department of Human, Biological and Translational Medical Sciences, School of Medicine, Hage Geingob Campus, University of Namibia, Windhoek, Namibia Summary: The contribution of prefrontal-hippocampal interactions to brain function of people infected with HIV may be aggravated by toxicities due to long-term use of antiretroviral agents. This study was designed to investigate the curative potential of Epigallotatechin gallate (EGCG) in the treatment of neurodegenerative disorders as a possible consequence of antiretroviral toxicity. Twenty-four adult male Wistar rats, weighing 80~100g, were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (EGCG 2.5mg/kg), D (EGCG 2.5mg/kg) + HAART) Brain histology, immunohistochemistry, and oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH),catalase (CAT) and malondialdehyde (MDA) were examined. The use of highly active antiretroviral therapy (HAART) showed extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus and prefrontal cortex. Expression of inflammasome cells was also evident in this group. MDA levels increased significantly with a significant reduction in the levels of GSH, as well as antioxidant enzyme (SOD and CAT) activities compared to other treatment groups. Treatment with EGCG resulted in partial neuronal restoration of histopathological alterations, and modulation of NLRP3 inflammasome in the hippocampus and prefrontal cortex. EGCG also showed significant improvements in terms of increased antioxidant levels of SOD, GSH, CAT and a reduced MDA level and well-preserved brain architecture. Epigallocatechin gallate improves brain morphology and function with a reversal of HAART-induced alterations. Keywords: Antioxidants, Antiretroviral, Inflammasome, Epigallocatechin gallate *Authors for correspondence: oluwatosin.ogedengbe@fuoye.edu.ng, Tel: +234(0)8163422223 Manuscript received- September 2021; Accepted- August 2022 DOI: https://doi.org/10.54548/njps.v37i2.7 ©Physiological Society of Nigeria INTRODUCTION The HIV/AIDS epidemic remains one of the most devastating health challenges that has had a significant impact on health outcomes and life expectancy in recent decades (Assefa and Gilks, 2020). There has been tremendous progress in the fight against this epidemic in recent years, with antiretrovirals serving as the standard treatment, thanks to the global commitment of the Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO) (Cobb et al., 2020, Zhang et al., 2020, Mai and Nguyen, 2022). In the global treatment of HIV/AIDS, highly active antiretroviral therapy (HAART) has been effective in revolutionizing the treatment of HIV infections and the quality of life of infected patients (Pongbulaan and Triyono, 2021). HAART, a tailor-made treatment regimen, consists of an alloy of various classes of antiretroviral drugs including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), fusion inhibitors (FIs) and chemokine receptor antagonists (CCR5 antagonists) (Ru and Tang, 2017). Current antiretroviral drugs are not curable and people with HIV will need to take them for the rest of their lives (Pasternak et al., 2021, Stern et al., 2021). However, the optimization of HAART, which requires long-term use, is not excluded from drug-related side effects (Matuszewska et al., 2021). HIV infection is associated with comorbidities that can be caused not only by HIV itself, but also by the