TitleCaffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity.
Publication TypeJournal Article
Year of Publication2014
AuthorsGray NE, Morré J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A
JournalJ Alzheimers Dis
Date Published2014
KeywordsAmyloid beta-Peptides, Cell Death, Cell Line, Transformed, Centella, Chlorogenic Acid, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Gene Expression Regulation, Enzymologic, Humans, Neuroblastoma, Neuroprotective Agents, Quinic Acid, tau Proteins

The accumulation of amyloid-β (Aβ) is a hallmark of Alzheimer's disease and is known to result in neurotoxicity both in vivo and in vitro. We previously demonstrated that treatment with the water extract of Centella asiatica (CAW) improves learning and memory deficits in Tg2576 mice, an animal model of Aβ accumulation. However the active compounds in CAW remain unknown. Here we used two in vitro models of Aβ toxicity to confirm this neuroprotective effect and identify several active constituents of the CAW extract. CAW reduced Aβ-induced cell death and attenuated Aβ-induced changes in tau expression and phosphorylation in both the MC65 and SH-SY5Y neuroblastoma cell lines. We confirmed and quantified the presence of several mono- and dicaffeoylquinic acids (CQAs) in CAW using chromatographic separation coupled to mass spectrometry and ultraviolet spectroscopy. Multiple dicaffeoylquinic acids showed efficacy in protecting MC65 cells against Aβ-induced cytotoxicity. Isochlorogenic acid A and 1,5-dicaffeoylquinic acid were found to be the most abundant CQAs in CAW, and the most active in protecting MC65 cells from Aβ-induced cell death. Both compounds showed neuroprotective activity in MC65 and SH-SY5Y cells at concentrations comparable to their levels in CAW. Each compound not only mitigated Aβ-induced cell death, but was able to attenuate Aβ-induced alterations in tau expression and phosphorylation in both cell lines, as seen with CAW. These data suggest that CQAs are active neuroprotective components in CAW, and therefore are important markers for future studies on CAW standardization, bioavailability, and dosing.

Alternate JournalJ. Alzheimers Dis.
PubMed ID24448790
PubMed Central IDPMC3973491
Grant ListAT002688 / AT / NCCIH NIH HHS / United States
3P30 AG000817 24 S1 / AG / NIA NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States
S10RR027878 / RR / NCRR NIH HHS / United States
P30 AG008017 / AG / NIA NIH HHS / United States
5 P30 AG008017 24 / AG / NIA NIH HHS / United States
S10 RR027878 / RR / NCRR NIH HHS / United States
T32 AT002688 / AT / NCCIH NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States