Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo

Hucklenbroich, Joerg; Klein, Rebecca; Neumaier, Bernd; Graf, Rudolf; Fink, Gereon R.; Schroeter, Michael; Rueger, Maria Adele

doi:10.1186/scrt500

Cited by 80 publications

(47 citation statements)

References 35 publications

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“…Besides transplanted cells, endogenous NSC can be mobilized from their neurogenic niches, namely the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampus. However, the intrinsic potential of endogenous NSC is insufficient and external stimuli are necessary to fully exploit their therapeutic potential (Arvidsson et al 2002;Lee et al 2012;Rueger et al 2012;Hucklenbroich et al 2014;Lindvall and Kokaia 2015;Rabenstein et al 2015;Braun et al 2016). The small NCAM-derived peptide FGL crosses the blood-brainbarrier and constitutes an attractive candidate molecule for enhancing the therapeutic potential of endogenous NSC and may thus open a new therapeutic vista.…”

Section: Discussionmentioning

confidence: 98%

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

Klein

Mahlberg

Ohren

et al. 2016

J Neuroimmune Pharmacol

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The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [F]-fluoro-L-thymidine ([F]FLT) to visualize endogenous NSC in vivo. FGL significantly increased endogenous NSC mobilization in the neurogenic niches as evidenced by in vivo and ex vivo methods, and it induced remyelination. Moreover, FGL affected neuroinflammation. Extending previous in vitro results, our data show that the NCAM mimetic peptide FGL mobilizes endogenous NSC after focal ischemia and enhances regeneration by amplifying remyelination and modulating neuroinflammation via affecting microglia. Results suggest FGL as a promising candidate to promote recovery after stroke.

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Section: Discussionmentioning

confidence: 98%

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

Klein

Mahlberg

Ohren

et al. 2016

J Neuroimmune Pharmacol

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“…Among turmerons, arturmerone is a major bioactive compound of C. longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease (Hucklenbroich et al 2014).…”

Section: Composition Of Essential Oilmentioning

confidence: 99%

Composition of Essential Oils in Turmeric Rhizome

Devkota

Rajbhandari

2016

Nepal Journal of Science and Technology

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Turmeric has been recognized as a pharmaceutical crop. It is valuable primarily for essential oil and curcumin content. Chemical composition of the essential oils obtained from the rhizome of turmeric was determined by GC/ MS technique. More than 75 compounds were detected and 67 of them were identified. They accounted for 98.59% of essential oil. The essential oil contained 15 monoterpenes (5.58%), 43 sesquiterpenes (84.37%) and 10 nonterpenic components (8.64%). The major constituents were ß-turmeron, a-turmeron, Epi-a-patschutene, ß-sesquiphellandrene, 1,4-dimethyl-2-isobutylbenzene, (±)-dihydro-ar-turmerone, zingiberene, E-a-atlantone and (-)-caryophyllene oxide. Thin layer chromatographic finger printing and quantitative determination of phenolics in acetone extract of commercially available turmeric samples were carried out using Folin-Ciocalteu colorimetric method. Gallic acid was used as the standard for the estimation of phenolics. All the investigated turmeric extracts contained relatively high amount of phenolics.

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“…Endogenous neurogenesis activating after infarction is insufficient to repair the damaged area of brain by itself [7] . Thus, promoting the proliferation and migration of endogenous/transplanted NSCs is a promising therapeutic target for ischemic infarction [8][9][10] . HIF-1α is constitutively expressed but is degraded rapidly by 26s proteasomes in normoxia in most cells.…”

Section: Research Articlementioning

confidence: 99%

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

Ye¹,

Chen²,

2017

Receptor Clin Invest

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Our previous studies have shown that transplantation of Hypoxia-inducible factor-1α (HIF-1α) gene modified neural stem cells (NSCs) reduced brain injury by improving the survival of NSCs and protecting the vascular system. HIF-1α plays pivotal roles during hypoxia, and its downstream pathways might be the primary mechanisms for the growth of NSCs. However, there are very few studies reported whether HIF-1α regulates NSCs migration. In this study, to test the hypothesis that HIF-1α modulates migration of NSCs after cerebral ischemia, we compared the injection of HIF-1α gene recombinant adenovirus, and control adenovirus in ischemia penumbra at 24 h after transient middle cerebral artery occlusion (tMCAO). BrdU labeled NSCs were transplanted in the lateral ventricle at the same time in both groups. The modified neurological severity score (NSS) was used to evaluate neurological deficits. Immunohistochemistry for HIF-1α, BrdU, Slit2 and Robo1 were performed. Comparing with vehicle group HIF-1α group showed better behavioral recovery on day 21 and 28. Expression of HIF-1α in HIF-1α group is higher than that in vehicle group. In HIF-1α group, more BrdU-positive cells were found than that in vehicle group. There are increased Slit2 in HIF-1α group. However, robo1, a receptor of Slits is decreased than that in vehicle group. Thus, we concluded that in cerebral ischemia rat model HIF-1α increased NSCs migration by inhibiting Slit2-Robo1 pathway, and improved the neurological behavior. In conclusion, our results indicate that HIF-1α may be a potential therapeutic target for ischemic stroke through promoting neuroregeneration.

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Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo

Cited by 80 publications

References 35 publications

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

Composition of Essential Oils in Turmeric Rhizome

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

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