Centella Asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action

Overview

Journal Int J Alzheimers Dis

Publisher Wiley

Date 2012 Apr 17

PMID 22506133

Citations 48

Authors

Amala Soumyanath

Yong-Ping Zhong

Edward Henson

Teri Wadsworth

James Bishop

Bruce G Gold

Joseph F Quinn

Affiliations

Soon will be listed here.

Abstract

Centella asiatica (CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

Citing Articles

improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice.

Matthews D, Khorani M, Bobe G, Caruso M, Magana A, Gray N J Alzheimers Dis Rep. 2025; 8(1):1611-1638.

PMID: 40034352 PMC: 11863750. DOI: 10.1177/25424823241296740.

Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice.

Varada S, Chamberlin S, Bui L, Brandes M, Gladen-Kolarsky N, Harris C Nutrients. 2025; 17(4).

PMID: 40005058 PMC: 11858387. DOI: 10.3390/nu17040729.

Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of .

Chamberlin S, Zweig J, Neff C, Marney L, Choi J, Yang L Pharmaceuticals (Basel). 2025; 18(1).

PMID: 39861082 PMC: 11768890. DOI: 10.3390/ph18010019.

Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms.

Anchimowicz J, Zielonka P, Jakiela S Int J Mol Sci. 2025; 26(1.

PMID: 39796234 PMC: 11720160. DOI: 10.3390/ijms26010380.

Neuroprotective effect against amyloidogenic transthyretin aggregates - Induced cytotoxicity on human neuroblastoma cell by phenolic-rich extract.

Eze F, Bunyapongpan A, Prapunpoj P Heliyon. 2024; 10(20):e39159.

PMID: 39640739 PMC: 11620063. DOI: 10.1016/j.heliyon.2024.e39159.

References

Wadsworth T, Koop D . Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem Pharmacol. 1999; 57(8):941-9. DOI: 10.1016/s0006-2952(99)00002-7. View

Woltjer R, McMahan W, Milatovic D, Kjerulf J, Shie F, Rung L . Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis. 2006; 25(2):427-37. DOI: 10.1016/j.nbd.2006.10.003. View

Morris R, Garrud P, Rawlins J, Okeefe J . Place navigation impaired in rats with hippocampal lesions. Nature. 1982; 297(5868):681-3. DOI: 10.1038/297681a0. View

Quinn J, Kulhanek D, Nowlin J, Jones R, Pratico D, Rokach J . Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: implications for clinical trials. Brain Res. 2005; 1037(1-2):209-13. DOI: 10.1016/j.brainres.2005.01.023. View

Ellman G, COURTNEY K, ANDRES Jr V, FEATHER-STONE R . A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7:88-95. DOI: 10.1016/0006-2952(61)90145-9. View

Wadsworth T, McDonald T, Koop D . Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol. 2001; 62(7):963-74. DOI: 10.1016/s0006-2952(01)00734-1. View

Gupta Y, Veerendra Kumar M, Srivastava A . Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav. 2003; 74(3):579-85. DOI: 10.1016/s0091-3057(02)01044-4. View

Lee M, Kim S, Sung S, Lim D, Kim H, Choi H . Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res Commun Mol Pathol Pharmacol. 2002; 108(1-2):75-86. View

Tariot P, Federoff H . Current treatment for Alzheimer disease and future prospects. Alzheimer Dis Assoc Disord. 2003; 17 Suppl 4:S105-13. DOI: 10.1097/00002093-200307004-00005. View

10.

Calon F, Lim G, Yang F, Morihara T, Teter B, Ubeda O . Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron. 2004; 43(5):633-45. PMC: 2442162. DOI: 10.1016/j.neuron.2004.08.013. View

11.

Veerendra Kumar M, Gupta Y . Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats. J Ethnopharmacol. 2002; 79(2):253-60. DOI: 10.1016/s0378-8741(01)00394-4. View

12.

James J, Dubery I . Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules. 2009; 14(10):3922-41. PMC: 6255425. DOI: 10.3390/molecules14103922. View

13.

Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong O, Piyawatkul N . Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol. 2008; 116(2):325-32. DOI: 10.1016/j.jep.2007.11.038. View

14.

Mook-Jung I, Shin J, Yun S, Huh K, Koh J, Park H . Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity. J Neurosci Res. 1999; 58(3):417-25. View

15.

Panza F, Frisardi V, Imbimbo B, DOnofrio G, Pietrarossa G, Seripa D . Bapineuzumab: anti-β-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. Immunotherapy. 2010; 2(6):767-82. DOI: 10.2217/imt.10.80. View

16.

Stackman R, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn J . Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment. Exp Neurol. 2003; 184(1):510-20. DOI: 10.1016/s0014-4886(03)00399-6. View

17.

Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius H . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003; 348(14):1333-41. DOI: 10.1056/NEJMoa013128. View

18.

Jew S, Yoo C, Lim D, Mook-Jung I, Jung M, Choi H . Structure-activity relationship study of asiatic acid derivatives against beta amyloid (A beta)-induced neurotoxicity. Bioorg Med Chem Lett. 2000; 10(2):119-21. DOI: 10.1016/s0960-894x(99)00658-7. View

19.

Bajpai M, Pande A, Tewari S, Prakash D . Phenolic contents and antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr. 2005; 56(4):287-91. DOI: 10.1080/09637480500146606. View

20.

Kappettu Gadahad M, Rao M, Rao G . Enhancement of hippocampal CA3 neuronal dendritic arborization by Centella asiatica (Linn) fresh leaf extract treatment in adult rats. J Chin Med Assoc. 2008; 71(1):6-13. DOI: 10.1016/s1726-4901(08)70066-2. View