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Open AccessArticle

Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model

Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Neuroscience Research and Development Group, Khon Kaen University, Khon Kaen 40002, Thailand
School of Life Sciences, Medical School, Queen’s Medical Centre, Nottingham University, Nottingham NG7 2RD, UK
Author to whom correspondence should be addressed.
Nutrients 2018, 10(8), 1053;
Received: 19 July 2018 / Revised: 7 August 2018 / Accepted: 8 August 2018 / Published: 9 August 2018
(This article belongs to the Special Issue Nutrients for Cardiometabolic Health and Brain Function)
5-fluorouracil or 5-FU (a chemotherapeutic medication) has been revealed to induce memory deficits in many cancer patients. Asiatic acid (AA) is a triterpenoid extract from Centella asiatica. This compound can ameliorate intracellular oxidative stress caused by chemotherapy drugs. Recent studies have shown that AA is capable of inhibiting neuronal generation and memory deficit produced by 5-FU chemotherapy. This study aimed to assess the molecular mechanisms of AA related to hippocampal neurogenesis and memory in rats receiving 5-FU. Male Sprague Dawley rats were given AA (30 mg/kg) orally and given 5-FU (25 mg/kg) by i.v. injection 5 times. Some rats were given AA for 20 days before and during 15-FU treatment (preventive), some received AA for 20 days after 5-FU treatment (recovery), and some underwent treatment with AA throughout the time of the experiment (throughout) for 40 days. Treatment with 5-FU caused significant reductions in Notch1, sex determining region Y-box 2 (SOX2), nestin, doublecortin (DCX), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels within the hippocampus. In addition, 5-FU significantly increased p21 positive cell number in the subgranular zone (SGZ) and malondialdehyde (MDA) levels in the hippocampus. Administration with both AA and 5-FU in prevention and throughout was able to prevent decreases in Notch1 SOX2, nestin, DCX, and Nrf2 caused by 5-FU. Treatment with AA also led to decreases in p21 positive cells and MDA levels in the hippocampus. These findings exhibit that AA has the ability to counteract the down-regulation of neurogenesis within the hippocampus and memory deficits caused by 5-FU via inhibiting oxidative stress and increasing neuroprotective properties. View Full-Text
Keywords: 5-fluorouracil; asiatic acid; neuroprotection; hippocampus 5-fluorouracil; asiatic acid; neuroprotection; hippocampus
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Welbat, J.U.; Chaisawang, P.; Pannangrong, W.; Wigmore, P. Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model. Nutrients 2018, 10, 1053.

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