Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity.
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.
Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
Nora E
NE
Gray
Department of Chemistry, Oregon State University, Corvallis, OR, USA.
Jeff
J
Morré
Department of Chemistry, Oregon State University, Corvallis, OR, USA.
Jeremiah
J
Kelley
Department of Chemistry, Oregon State University, Corvallis, OR, USA.
Claudia S
CS
Maier
Department of Pharmaceutical Sciences and the Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
Jan F
JF
Stevens
Department of Neurology, Oregon Health and Science University, Portland, OR, USA Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, USA.
Joseph F
JF
Quinn
Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
Amala
A
Soumyanath
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D028041:Centella / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; C472707:caffeoylquinic acid; D016875:tau Proteins; D011801:Quinic Acid; C469310:isochlorogenic acid; D002726:Chlorogenic Acid
Amyloid-β toxicity; Centella asiatica; caffeoylquinic acids; neuroprotection; tau