Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells

Wanakhachornkrai, Oraphan; Pongrakhananon, Varisa; Chunhacha, Preedakorn; Wanasuntronwong, Aree; Vattanajun, Anusara; Tantisira, Boonyong; Chanvorachote, Pithi; Tantisira, Mayuree H.

doi:10.1186/1472-6882-13-204

Cited by 39 publications

(39 citation statements)

References 33 publications

(34 reference statements)

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“…Based on the previous report of ECa 233 increased activity of ERK and Akt in human neuroblastoma (Wanakhachornkrai et al, 2013), we further investigated effects of ECa 233 on the expression of FAK, Akt, and MAPK in HaCaT. As expected, ECa 233 was found to enhance the phosphorylation of FAK, Akt, (Figure 4) and ERK, p38 MAPK ( Figure 5).…”

Section: Discussionmentioning

confidence: 57%

Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling

Singkhorn

Tantisira

Tanasawet

et al. 2018

Phytotherapy Research

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Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay. Formation of filopodia, a key protein in cell migration as well as signaling pathways possibly involved were subsequently assessed. It was found that HaCaT cell migration was significantly enhanced by ECa 233 in a concentration- and time-dependent manner. The filopodia formations were accordingly increased in exposure to ECa 233 at concentrations of 0.1-100 μg/ml. Furthermore, ECa 233 was found to significantly upregulate the expression of Rac1 and RhoA and to induce phosphorylation of FAK and Akt as well as ERK and p38 MAPK. Taken all together, it is suggestive that ECa 233 induces cell migration and subsequently promotes wound healing activity, through the activation of FAK, Akt, and MAPK signaling pathways thereby supporting the role of ECa 233 to be further developed for the clinical treatment of wound.

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Section: Discussionmentioning

confidence: 57%

Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling

Singkhorn

Tantisira

Tanasawet

et al. 2018

Phytotherapy Research

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“…The complex regulation of spine formation and arborization potentially implicates a variety of biological pathways and processes including histone modification, transcription factors, microRNAs, kinases, hormones and cell surface receptors [37, 38]. Although details on its molecular mechanisms are limited, Centella asiatica has been shown to activate ERK1/2 and AKT in neuroblastoma cells [39, 40], two pathways that have been shown to affect dendritic morphology as well [41, 42]. Studies are ongoing in our lab to evaluate signal transduction pathways affected by CAW and the role they play in the neuroprotective effects of the extract.…”

Section: Discussionmentioning

confidence: 99%

Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification

Gray

Zweig

Murchison

et al. 2017

Neuroscience Letters

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The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer’s disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer’s disease.

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“…The neuroprotective effects of Centella asiatica have been well documented [20, 61-64], yet these effects have usually been attributed to the bioactive triterpenes (asiatic acid, madecassic acid, asiaticoside, madacassoside) present in the plant. We previously reported that our original extract of CAW does not contain these triterpenes [18].…”

Section: Discussionmentioning

confidence: 99%

Caffeoylquinic Acids in Centella asiatica Protect against Amyloid-β Toxicity

Gray

Morré

Kelley

et al. 2014

JAD

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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.

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Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells

Cited by 39 publications

References 33 publications

Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling

Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling

Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification

Caffeoylquinic Acids in Centella asiatica Protect against Amyloid-β Toxicity

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