Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression

Schuck, Florian; Schmitt, Ulrich; Reinhardt, Sven; Freese, Christian; Lee, Ik‐Soo; Thines, Eckhard; Efferth, Thomas

doi:10.1016/j.phymed.2015.08.001

Cited by 11 publications

(5 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, identification of novel ADAM10 enhancers from phytomedical collections via reporter gene assay has been demonstrated to be a promising approach 19 , 20 . By analyzing drugs already approved by the FDA, rapid translation into clinical studies is likely, enhancing the attractiveness of such re-purposing strategies.…”

Section: Resultsmentioning

confidence: 99%

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Reinhardt

Stoye

Luderer

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPP-alpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer’s disease (AD). Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-plaque formation and learning and memory deficits in AD mouse models. Therefore, it has been assumed that ADAM10 might represent a valuable target in AD therapy. Here we screened a FDA-approved drug library and identified disulfiram as a novel ADAM10 gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP-alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute disulfiram treatment of Alzheimer model mice induced ADAM10 expression in peripheral blood cells, reduced plaque-burden in the dentate gyrus and ameliorated behavioral deficits. Alcohol-dependent patients are subjected to disulfiram-treatment to discourage alcohol-consumption. In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in Alzheimer patients in the future.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Reinhardt

Stoye

Luderer

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Consequently, it prevents the formation of toxic amyloid beta peptides, but also provides a neuroprotective fragment of the amyloid precursor protein (sAPPalpha). However, a challenge remains due to its limitation in crossing the blood-brain barrier [21], making the design of new formulations a necessity in the future.…”

Section: Neuroprotective Effectsmentioning

confidence: 99%

Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy

et al. 2022

View full text Add to dashboard Cite

Viniferin is a resveratrol derivative. Resveratrol is the most prominent stilbenoid synthesized by plants as a defense mechanism in response to microbial attack, toxins, infections or UV radiation. Different forms of viniferin exist, including alpha-viniferin (α-viniferin), beta-viniferin (β-viniferin), delta-viniferin (δ-viniferin), epsilon-viniferin (ε-viniferin), gamma-viniferin (γ-viniferin), R-viniferin (vitisin A), and R2-viniferin (vitisin B). All of these forms exhibit a range of important biological activities and, therefore, have several possible applications in clinical research and future drug development. In this review, we present a comprehensive literature search on the chemistry and biosynthesis of and the diverse studies conducted on viniferin, especially with regards to its anti-inflammatory, antipsoriasis, antidiabetic, antiplasmodic, anticancer, anti-angiogenic, antioxidant, anti-melanogenic, neurodegenerative effects, antiviral, antimicrobial, antifungal, antidiarrhea, anti-obesity and anthelminthic activities. In addition to highlighting its important chemical and biological activities, coherent and environmentally acceptable methods for establishing vinferin on a large scale are highlighted to allow the development of further research that can help to exploit its properties and develop new phyto-pharmaceuticals. Overall, viniferin and its derivatives have the potential to be the most effective nutritional supplement and supplementary medication, especially as a therapeutic approach. More researchers will be aware of viniferin as a pharmaceutical drug as a consequence of this review, and they will be encouraged to investigate viniferin and its derivatives as pharmaceutical drugs to prevent future health catastrophes caused by a variety of serious illnesses.

show abstract

“…To analyze the potential toxic impact of fungal components on the viability of neuronal cells, we chose SH-SY5Y cells that serve as representatives of neurons in many investigations [19]. Cells were treated for 24 h with the extracts in an initial concentration of 5 ng/µL and ATP content, mirroring viability, measured with the Cell Titer Glo Assay (Promega, [20,21]). A hit was defined if within at least three independent experiments, treatment with the extract resulted in a value <100%-3xSD% and a SD between experiments of <10%.…”

Section: Resultsmentioning

confidence: 99%

“…The ITS sequence of IBWF D03003 has 100% identity with three CBS strains of Penicillium coprobium (CBS 129797; CBS 561.90; CBS 210.70). The fungal extract was analyzed and fractionated as described previously [20]. Briefly, 400 µg of extract were injected and fractions separated on HPLC to obtain 92 fractions comprising eluent of 15 s. Subsequently, fractions were evaporated and stored at −20 °C until further use.…”

Section: Methodsmentioning

confidence: 99%

Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons

et al. 2019

View full text Add to dashboard Cite

The identification and characterization of fungal commensals of the human gut (the mycobiota) is ongoing, and the effects of their various secondary metabolites on the health and disease of the host is a matter of current research. While the neurons of the central nervous system might be affected indirectly by compounds from gut microorganisms, the largest peripheral neuronal network (the enteric nervous system) is located within the gut and is exposed directly to such metabolites. We analyzed 320 fungal extracts and their effect on the viability of a human neuronal cell line (SH-SY5Y), as well as their effects on the viability and functionality of the most effective compound on primary enteric neurons of murine origin. An extract from P. coprobium was identified to decrease viability with an EC50 of 0.23 ng/µL in SH-SY5Y cells and an EC50 of 1 ng/µL in enteric neurons. Further spectral analysis revealed that the effective compound was patulin, and that this polyketide lactone is not only capable of evoking ROS production in SH-SY5Y cells, but also diverse functional disabilities in primary enteric neurons such as altered calcium signaling. As patulin can be found as a common contaminant on fruit and vegetables and causes intestinal injury, deciphering its specific impact on enteric neurons might help in the elaboration of preventive strategies.

show abstract

Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression

Cited by 11 publications

References 41 publications

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy

Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons

Contact Info

Product

Resources

About