Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells
Open accessAbstract
Aim To investigate whether asiatic acid (AA), a pentacyclic triterpene in Centella asiatica, exerted neuroprotective effects in vitro and in vivo, and to determine the underlying mechanisms.Methods Human neuroblastoma SH-SY5Y cells were used for in vitro study. Cell viability was determined with the MTT assay. Hoechst 33342 staining and flow cytometry were used to examine the apoptosis. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured using fluorescent dye. PGC-1α and Sirt1 levels were examined using Western blotting. Neonatal mice were given monosodium glutamate (2.5 mg/g) subcutaneously at the neck from postnatal day (PD) 7 to 13, and orally administered with AA on PD 14 daily for 30 d. The learning and memory of the mice were evaluated with the Morris water maze test. HE staining was used to analyze the pyramidal layer structure in the CA1 and CA3 regions.Results Pretreatment of SH-SY5Y cells with AA (0.1-100 nmol/L) attenuated toxicity induced by 10 mmol/L glutamate in a concentration-dependent manner. AA 10 nmol/L significantly decreased apoptotic cell death and reduced reactive oxygen species (ROS), stabilized the mitochondrial membrane potential (MMP), and promoted the expression of PGC-1α and Sirt1. In the mice models, oral administration of AA (100 mg/kg) significantly attenuated cognitive deficits in the Morris water maze test, and restored lipid peroxidation and glutathione and the activity of SOD in the hippocampus and cortex to the control levels. AA (50 and 100 mg/kg) also attenuated neuronal damage of the pyramidal layer in the CA1 and CA3 regions.Conclusion AA attenuates glutamate-induced cognitive deficits of mice and protects SH-SY5Y cells against glutamate-induced apoptosis in vitro.
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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 [2]
Certain CAW active compounds increase learning and memory and provide neuroprotection in rodents in vivo.
“The neurological effects of certain CAW active compounds are also observed in vivo, increasing learning and memory while providing neuroprotection in rodents [2,13,112].”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [2]
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“The neurological effects of certain CAW active compounds are also observed in vivo, increasing learning and memory while providing neuroprotection in rodents [2,13,112].”
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- Authors
- Xu, M.-F., Xiong, Y.-Y., Liu, J.-K., Qian, J.-J., Zhu, L., & Gao, J.
- Affiliations
- Jiangsu University (CN)
- Affiliated Hospital of Jiangsu University (CN)
- Nantong University (CN)
- Corresponding author
- Gao, Jing
- Venue
- Acta Pharmacologica Sinica
- Published
- 2012-03-26
- Volume
- 33
- Issue
- 5
- Pages
- 578-587
- ISSN
- 0253-9756 (ISSN-L)
- 1671-4083
- 1745-7254
- PMC
- PMC4010358
- OpenAlex
- W1969457041
- Cited by
- 156
- References
- 56
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 10 · 2023: 18 · 2022: 12 · 2021: 17 · 2020: 13 · 2019: 11 · 2018: 12 · 2017: 16 · 2016: 10 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 14.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Pharmacologica Sinica (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31171143)
- Jiangsu University
- Ministry of Education, India
- University of California, Irvine
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- asiatic acid, Centella asiatica, pentacyclic triterpenes, neuroprotection, glutamate excitotoxicity, cognitive impairment, apoptosis, SH-SY5Y cells, mitochondrial membrane potential, reactive oxygen species, PGC-1α, SIRT1, lipid peroxidation, glutathione, superoxide dismutase, hippocampus, learning and memory
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Animals, Newborn, Behavior, Animal, Cell Survival, Cognition, Dementia, Disease Models, Animal, Dose-Response Relationship, Drug, Flow Cytometry, Glutathione, Heat-Shock Proteins, Humans, Memory, Neuroblastoma, Sodium Glutamate, Superoxide Dismutase, Time Factors, Transcription Factors, Blotting, Western, Lipid Peroxidation, Apoptosis, Oxidative Stress, Neuroprotective Agents, Nootropic Agents, Centella, Cell Line, Tumor, Mice, Membrane Potential, Mitochondrial, Pentacyclic Triterpenes, CA1 Region, Hippocampal, Sirtuin 1, CA3 Region, Hippocampal
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