The accumulation of β-amyloid (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.
Cellulose nanocrystals (CNCs) have received considerable attention recently because CNCs can be produced from renewable materials such as straw, wood, cotton, and sea animals (tunicates). CNCs are one of the stiffest organic materials, with an estimated tensile modulus (E) of 80-160 GPa depending on the starting material. In addition, composites incorporating CNCs have been fabricated from a variety of polymer matrices and CNCs have been shown to increase the E significantly and to a lesser extent the tensile strength (TS). A copolymer of poly(vinylidene fluoride) (PVDF), PVDF-co-hexafluoropropylene) (PVDFHFP), has received interest over the years in the area of lithium ion battery separator technology. However, the mechanical properties of neat PVDFHFP do not meet the necessary requirements for commercial separators, especially the low E. In this work, novel PVDHFHFP/CNC nanocomposite films were fabricated and characterized. It was found that incorporation of CNCs improves the E and TS. The improvement in mechanical properties of PVDFHFP upon addition of CNCs makes PVDFHFP a more suitable candidate for polymer separators in lithium ion batteries.
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