Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model
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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.
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Compounds in CA such as ferulic acid and asiatic acid induce Nrf2 and its ARE-regulated targets, exhibiting a neuroprotective effect.
“Compounds such as the phenolic ferulic acid [89,90] and the triterpene asiatic acid [2,91], induce Nrf2 and its ARE-regulated targets, exhibiting a neuroprotective effect [92,93,94,95].”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [92]
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References 63 · Cited by 42
- Authors
- Welbat, J. U., Chaisawang, P., Pannangrong, W., & Wigmore, P.
- Affiliations
- Khon Kaen University (TH)
- University of Nottingham (GB)
- Corresponding author
- Welbat, Jariya Umka
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2018-08-09
- Volume
- 10
- Issue
- 8
- Pages
- 1053
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6115773
- OpenAlex
- W2886480677
- Cited by
- 42
- References
- 63
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 3
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Thailand Research Fund (TRG5780086)
- Neuroscience Research and Development Group at Khon Kaen University (012/2559)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- asiatic acid, 5-fluorouracil, chemotherapy-induced neurotoxicity, hippocampal neurogenesis, oxidative stress, memory impairment, Notch1, SOX2, Nrf2, p21, malondialdehyde, subgranular zone, neuroprotection
- MeSH terms
- Doublecortin Protein, Animals, Antimetabolites, Antineoplastic, Antioxidants, Behavior, Animal, Disease Models, Animal, Fluorouracil, Hippocampus, Male, Memory, Memory Disorders, Nerve Tissue Proteins, Signal Transduction, Rats, Sprague-Dawley, Oxidative Stress, Neuroprotective Agents, Pentacyclic Triterpenes, Neurogenesis, Cell Cycle Checkpoints
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