12 January - 20 June 2016

Compounds found in green tea and red wine may block formation of toxic metabolites

A study by researchers from the Department of Molecular Microbiology and Biotechnology at Tel Aviv University, published in the journal Communications Chemistry, is reporting that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites in those with certain congenital metabolic disorders.

A study by researchers from the Department of Molecular Microbiology and Biotechnology at Tel Aviv University, published in the journal Communications Chemistry, is reporting that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites in those with certain congenital metabolic disorders.

 The formation of protein and polypeptide amyloid fibrils has been associated with numerous neurodegenerative diseases such as Alzheimer’s. Additionally, certain congenital metabolic disorders result in those affected having to adhere to a strict diet to prevent the formation of such fibrils. The current study notes that one of the most promising therapeutic approaches for dealing with amyloidogenic diseases is the” inhibition of amyloid formation by small-molecule inhibitors” which inhibit the self-assembly processes for amyloid fibril formation and that polyphenols are thought to inhibit amyloid formation in this way.

Gazit et al. wanted to focus on whether polyphenols such as EGCG (found in green tea) and tannic acid (TA) (found in red wine), both known to prevent amyloid formation, could help prevent formation of the toxic metabolites in metabolic diseases. The studies performed were focused on varying the concentration of the two polyphenols in the presence of three amyloidogenic metabolites, namely, adenine, phenylalanine and tyrosine and looking at fibril formation on a neuronal cell model within six hours.  A variety of imaging techniques including thioflavin-T (ThT) fluorescence assays, Transmission Electron Microscopy (TEM) and Extreme High-Resolution Scanning Electron Microscopy (XHR-SEM)) were used. The researchers found evidence of a dose-dependent inhibition of aggregate formation with increasing concentration of polyphenols, with the highest concentration level resulting in near complete inhibition of aggregate formation. Gazit et al. also found that at lower concentrations, TA exhibited a stronger inhibitory effect than EGCG with the adenine and tyrosine metabolites, however, when it came to phenylalanine, EGCG resulted in substantial inhibition across all concentrations whereas TA had almost no effect at its lowest concentration, a significant reduction at the middle concentration and total inhibition at the highest.

Gazit et al. went on to examine the correlation between the inhibitory potential observed and cytotoxicity. SH-SY5Y cells were incubated for 24 hours with amyloid fibrils of the three metabolites in the presence of the polyphenol inhibitors. Again, a dose-dependent correlation was found with the greater presence of inhibitors increasing cell viability. They did find however, that levels of cell viability restoration were not reproduced when the inhibitors were added after six hours of prior treatment with fibrils, concluding this “indicates that the restoration of cell viability was a result of lack of metabolites assembly formation owing to the addition of EGCG or TA”. Following on from this, further research into the mechanism of fibril formation inhibition and cell viability restoration involved the addition of the inhibitors at 0, 0.5, 1, and 2 hours. Their results showed that, although both EGCG and TA act as inhibitors, they have different mechanisms such that EGCG can prevent aggregation at both the early and later stages (up to and including the 2-hour addition), whereas, TA only has a significant effect at the early stages of fibril formation. Gazit et al. attributed these differences to EGCG’s molecular packing. With relatively smaller dimensions than TA, it is able to bind to the amyloid’s ordered lattice to a larger extent in higher concentrations.

In conclusion, the study notes that “the less-explored concept of error of metabolism disorders as amyloid diseases may thus lead to the development of new therapeutic strategies, in addition to the current dietary restrictions”. One of the authors of the study, Shira Shaham-Niv, is quoted in a press release as saying that the teams work has “led to an overhaul in the research community's understanding of metabolic diseases”. Shaham-Niv added that “Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies. We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer”

RSSL can analyse green tea for catechins, including epigallocatechin-gallate (EGCG) and epigallocatechin (EGC). To find out more please contact Customer Services telephone 0118 918 4076 or e-mail enquiries@rssl.com

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