The protective effect of Centella asiatica and its constituent, araliadiol on neuronal cell damage and cognitive impairment.

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. C. asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. C. asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, C. asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that C. asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.

• Authors: Honoka Fujimori, Takuya Ohba, Masashi Mikami, Shinsuke Nakamura, Kenichi Ito, Hiroyuki Kojima, Tatsuji Takahashi, Arunasiri Iddamalgoda, Masamitsu Shimazawa, Hideaki Hara
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 148 Issue 1 Pg. 162-171 (Jan 2022) ISSN: 1347-8648 [Electronic] Japan
• PMID: 34924122 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Centella asiatica extract
• Endoplasmic Reticulum Chaperone BiP
• Hspa5 protein, mouse
• Membrane Glycoproteins
• Neuroprotective Agents
• Plant Extracts
• Reactive Oxygen Species
• Triterpenes
• endoplasmin
• PERK kinase
• eIF-2 Kinase

Topics

• Administration, Oral
• Animals
• Cell Death (drug effects)
• Cells, Cultured
• Centella (chemistry)
• Cognitive Dysfunction (drug therapy, etiology, prevention & control)
• Endoplasmic Reticulum Chaperone BiP (metabolism)
• Endoplasmic Reticulum Stress
• Hippocampus (cytology, pathology)
• Male
• Membrane Glycoproteins (metabolism)
• Mice, Inbred ICR
• Neurons (drug effects, pathology)
• Neuroprotective Agents
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Phytotherapy
• Plant Extracts (administration & dosage, isolation & purification, pharmacology)
• Reactive Oxygen Species (metabolism)
• Triterpenes (administration & dosage, isolation & purification, pharmacology)
• eIF-2 Kinase (metabolism)