Impact of plant extracts tested in attention‐deficit/hyperactivity disorder treatment on cell survival and energy metabolism in human neuroblastoma SH‐SY5Y cells

Abstract

Plant extracts like Hypericum perforatum and Pycnogenol ® have been tested as alternatives to the classical ADHD drugs. It has been possible to describe neuroprotective effects of such plant extracts. A reduction of ADHD symptoms could be shown in clinical studies after the application of Pycnogenol ® , which is a pine bark extract. The impacts of the standardized herbal extracts Hypericum perforatum, Pycnogenol ® and Enzogenol ® up to a concentration of 5.000 ng/ml on cell survival and energy metabolism in human SH-SY5Y neuroblastoma cells has been investigated in the present examination. Hypericum perforatum significantly decreased survival of cells after treatment with a concentration of 5000 ng/ml, whereas lower concentrations exerted no significant effects. Pycnogenol ® induced a significant increase of cell survival after incubation with a concentration of 32.25 ng/ml and a concentration of 250 ng/ml. Other applied concentrations of Pycnogenol ® failed to exert significant effects. Treatment with Enzogenol ® did not lead to significant changes in cell survival.Concerning energy metabolism, treatment of cells with a concentration of 5000 ng/ml Hypericum perforatum led to a significant increase of ATP levels, whereas treatment with a concentration of 500 ng/ml had no significant effect. Incubation of cells with Pycnogenol ® and Enzogenol ® exerted no significant effects.None of the tested substances caused any cytotoxic effect when used in therapeutically-relevant concentrations. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The extract of Hypericum perforatum is known to exert both antioxidative properties and protective effects (e.g. Benedi et al., 2004;Breyer at al., 2007; El-Sherbiny et al., 2003;Sanchez-Reus et al., 2007). However, no improvement of ADHD symptoms after a treatment of eight weeks has been found in a recently published randomised, double-blind, placebocontrolled study (Weber et al., 2008). The patients had not received any other drugs during this study.A plant extract which has been discussed extensively in terms of ADHD treatment over the last few years is Pycnogenol ® . Pycnogenol ® stands for a bark extract of the French maritime pine (Pinus pinaster) and mainly consists of procyanidines as well as catechins and phenolic acids (Packer et al., 1999). The antioxidant activities of this extract have been described. It could be been shown in vitro that Pycnogenol® is a free radical scavenger (Packer et al., 1999), that it stimulates activities of antioxidant enzymes like Cu, Zn superoxide dismutase (Fitzpatrick et al., 1998) and that it influences the glutathione metabolism (Berryman et al., 2004 , 2006; Joshi et al., 2006;Ross, et al., 2003; Spahis et al., 2008) as well as in adults suffering from ADHD (Bulut et al., 2007;Selek et al., 2008). Also Ginko biloba has been shown to be effective for tre...

Psychiatric Disorders and Polyphenols: Can They Be Helpful in Therapy?

“…The same cells were used in another experiment, in which Pycnogenol and extract from Hypericum perforatum (St. John's wort) were used as alternatives to the classical ADHD drugs. Pycnogenol exerted no significant effect on ATP level but increased cell survival at the concentrations 32.25 and 250 ng/mL [ 124 ].…”

Using Cell Cultures for the Investigation of Treatments for Attention Deficit Hyperactivity Disorder: A Systematic Review

“…Mitochondrial activity was evaluated at different times of exposure and substance concentrations. The final results revealed that none of the substances reduced neuronal cell survival compared with control cells [8,9,11]. The activity of LDH enzyme was measured by only one study [11] in which cell death was induced by concentrations of amphetamine (3.50 mM and 5.00 mM).…”

“…From the 16 studies selected in our systematic search, five (31.3%) used the SH-SY5Y neuroblastoma [7,8,10,33,34] and two (12.5%) used the PC12 cell line [18,32]. This first strain is a sub-line of the SK-N-SH cell, which was established in culture in 1970 from human metastatic neuroblastoma tissue [35].…”

“…Three studies [8,9,11] quantitatively evaluated cellular viability the neuroblastoma SH-SY5Y using the 3-(4,5dimethylthiazol-2yl)-2,5-diphenyl tetrazoline bromide (MTT) assay, measuring lactate dehydrogenase (LDH) activity, or evaluating the adenosine triphosphate (ATP) content.…”

Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder

“…St. John's wort and pycnogenol have been tested as therapeutic alternatives to treat ADHD. A significant increase of SH-SY5Y cell survival was induced by pycnogenol, which did not cause any cytotoxic effect when used in therapeutically relevant concentrations; also, treatment with St. John's wort significantly increased ATP levels [100]. Oroxylin A is a flavonoid isolated from the root of Scutellaria baicalensis Georgi, a herb found in East Asia.…”