Centella asiatica extract protects against amyloid β_(1-40)-induced neurotoxicity in neuronal cells by activating the antioxidative defence system

10.1016/j.jtcme.2015.07.002

Chien-Li Chen；Wen-Hao Tsai；Chun-Jen Chen；Tzu-Ming Pan

Alzheimer's disease ； Amyloid β ； Centella asiatica ； Antioxidative defence system ； Oxidative stress ； Reactive oxygen species

Journal of Traditional and Complementary Medicine

6卷4期（2016 / 10 / 01）

362 - 369

英文

Centella asiatica (雷公根léi gōng gēn) is a traditional medicinal herb with high antioxidant activity, which decreases amyloid-β (Aβ) deposition in the brain. At the same time, aggregated Aβ-induced oxidative stress is the trigger in the pathogenesis of Alzheimer's disease (AD). Here, we investigated the ability of C. asiatica ethanol extract (CAE) to protect PC12 and IMR32 cells from Aβ_(1-40)-induced production of reactive oxygen species (ROS) and concomitant neurotoxicity. Aggregated Aβ_(1-40) treatment resulted in reduced cell viability, which can be reversed by cotreatment with 25, 50, and 100 μg/mL CAE. Moreover, CAE eliminated the Aβ_(1-40)-mediated increase in ROS production. Thus, CAE-mediated protection against aggregated Aβ_(1-40)-induced neurotoxicity is attributable to modulation of the antioxidative defense system in cells, including the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and levels of glutathione and glutathione disulfide by CAE. This emphasizes the potential therapeutic and preventive value of CAE in the treatment of AD.

1. Aliev, G,Seyidova, D,Lamb, BT(2003).Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer's disease-like pathology in transgenic mice.Neurol Res.,25,665-674.
2. Anantharaman, M,Tangpong, J,Keller, JN(2006).b-Amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLh/NLh X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease.Am J Pathol,168,1608-1618.
3. Behl, C,Davis, JB,Lesley, RS,Schubert, D(1994).Hydrogen peroxide mediates amyloid beta protein toxicity.Cell,77,817-827.
4. Clementi, ME,Marini, S,Coletta, M,Orsini, F,Giardina, B,Misiti, F(2005).Abeta (31-35) and Abeta (25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: role of the redox state of methionine-35.FEBS Lett.,579,2913-2918.
5. Conti, M,Couturier, M,Lemonnier, A,Lemonnier, F(1993).Effects of alpha-tocopherol on antioxidant enzyme activity in human fibroblast cultures.Int J Vitam Nutr Res.,63,71-76.
6. Demuro, A,Parker, I,Stutzmann, G.(2010).Calcium signaling and amyloid toxicity in Alzheimer disease.J Biol Chem,285,12463-12468.
7. Dhanasekaran, M,Holcomb, LA,Hitt, AR(2009).Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model.Phytother Res,23,14-19.
8. Donahue, JE,Flaherty, SL,Johanson, CE(2006).RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease.Acta Neuropathol.,112,405-415.
9. Gunasingh, MJ,Philip, JE,Ashok, BS(2008).Melatonin prevents amyloid proto-fibrillar induced oxidative imbalance and biogenic amine catabolism.Life Sci.,83,96-102.
10. James, JT,Dubery, IA(2009).Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban.Molecules,14,3922-3941.
11. Jeong, JC,Yoon, CH,Lee, WH(2005).Effects of Bambusae concretio Salicea (Chunchukhwang) on amyloid beta-induced cell toxicity and antioxidative enzymes in cultured rat neuronal astrocytes.J Ethnopharmacol,98,259-266.
12. Lee, CL,Wang, JJ,Pan, TM(2008).Red mold rice extract represses amyloid beta peptide-induced neurotoxicity via potent synergism of anti-inflammatory and anti-oxidative effect.Appl Microbiol Biotechnol,79,829-841.
13. Manczak, M,Anekonda, TS,Henson, E,Park, BS,Quinn, J,Reddy, PH(2006).Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression.Hum Mol Genet.,15,1437-1449.
14. Mattson, MP(2004).Pathways towards and away from Alzheimer's disease.Nature,430,631-639.
15. Mukherjee, S,Dugad, S,Bhandare, R(2011).Evaluation of comparative free-radical quenching potential of Brahmi (Bacopa monnieri) and Mandookparni (Centella asiatica).Int J Ayurveda Res,32,258-264.
16. Rafamantnana, MH,Rozet, E,Raoelison, GE(2009).An improved HPLC-UV method for the simultaneous quantification of triterpenic glycosides and aglycones in leaves of Centella asiatica (L.) Urb (APIACEAE).J Chromatogr B Anal Technol Biomed Life Sci,887,2396-2402.
17. Saido, TC,Iwata, N.(2006).Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease. Towards presymptomatic diagnosis, prevention and therapy.Neurosci Res.,54,235-253.
18. Sakono, M,Zako, T(2010).Amyloid oligomers: formation and toxicity of Abeta oligomers.FEBS J.,277,1348-1358.
19. Scheuner, D,Eckman, C,Jensen, M(1996).Secreted amyloid betaprotein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.Nat Med,2,864-870.
20. Schupf, N,Patel, B,Silverman, W(2001).Elevated plasma amyloid beta-peptide 1-42 and onset of dementia in adults with down syndrome.Neurosci Lett,301,199-203.
21. Selkoe, DJ(2001).Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein.J Alzheimers Dis.,3,75-80.
22. Smith, JV,Luo, Y(2003).Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761.J Alzheimers Dis,5,287-300.
23. Soumyanath, A,Zhong, YP,Henson, E(2012).Centella asiatica extract improves behavioral deficits in a mouse model of Alzheimer's disease: investigation of a possible mechanism of action.Int J Alzheimers Dis,2012,381974.
24. Subathra, M,Shila, S,Devi, MA,Panneerselvam, C(2005).Emerging role of Centella asiatica in improving age-related neurological antioxidant status.Exp Gerontol,40,707-715.
25. van Dijk, EJ,Prins, ND,Vermeer, SE(2004).Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions.Ann Neurol,55,570-575.
26. van Marum, RJ(2008).Current and future therapy in Alzheimer's disease.Fundam Clin Pharmacol,22,265-274.
27. van Oijen, M,Hofman, A,Soares, HD,Koudstaal, PJ,Breteler, MM(2006).Plasma Aβ1-40 and Aβ1-42 and the risk of dementia: a prospective case-cohort study.Lancet Neurol.,5,655-660.
28. Veerendra-Kumar, MH,Gupta, YK(2002).Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats.J Ethnopharmacol,79,253-260.
29. Wilcock, G,Howe, I,Coles, H(2003).A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease.Drugs Aging,20,777-789.
30. Younkin, SG.(1998).The role of A beta 42 in Alzheimer's disease.J Physiol Paris,92,289-292.

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