Photostability of sennosides and their aglycones in solution.

INTRODUCTION: Sennosides are the main active constituents of the dried leaves and/or pods of Senna alexandrina Mill. that are used as laxatives. A hypothesis is that aglycones are formed during the degradation of sennosides. However, it is unknown, whether this happens under visible light exposure and how photosensitive sennosides behave in solution. OBJECTIVES: Pure anthraquinone glycosides were tested on their behaviour during sample preparation in the lab under visible light exposure in dependence on the instability of the solvent. MATERIALS AND METHODS: Samples before and after exposure were analysed using UHPLC with UV/Vis and MS detection. RESULTS: Under visible light protection, the solutions were stable for 14 days at room temperature whereas a loss of 20%-60% was measured after 1 day of light exposure. The loss of sennosides due to degradation can be as fast as up to 2%-2.5% per hour, which might have a tremendous impact on phytochemical analysis results during the course of an analysis. The formation of aglycones was not observed in the degradation of sennosides and rhein-8-O-glucoside. CONCLUSION: Aglycones could not be found as a result of the forced degradation. The solutions of sennosides clearly need to be protected from light to obtain reliable analytical results, and light protection is a major point for the stability of liquid preparations.

Is comfrey root more than toxic pyrrolizidine alkaloids? Salvianolic acids among antioxidant polyphenols in comfrey (Symphytum officinale L.) roots.

Comfrey root preparations are used for the external treatment of joint distortions and myalgia, due to its analgesic and anti-inflammatory properties. Up to date, key activity-determining constituents of comfrey root extracts have not been completely elucidated. Therefore, we applied different approaches to further characterize a comfrey root extract (65% ethanol). The phenolic profile of comfrey root sample was characterized by HPLC-DAD-QTOF-MS/MS. Rosmarinic acid was identified as main phenolic constituent (7.55 mg/g extract). Moreover, trimers and tetramers of caffeic acid (isomers of salvianolic acid A, B and C) were identified and quantified for the first time in comfrey root. In addition, pyrrolizidine alkaloids were evaluated by HPLC-QQQ-MS/MS and acetylintermedine, acetyllycopsamine and their N-oxides were determined as major pyrrolizidine alkaloids in the comfrey root sample. Lastly, the antioxidant activity was determined using four assays: DPPH and ABTS radicals scavenging assays, reducing power assay and 15-lipoxygenase inhibition assay. Comfrey root extract exhibited significant antioxidant activities when compared to known antioxidants. Thus, comfrey root is an important source of phenolic compounds endowed with antioxidant activity which may contribute to the overall bioactivity of Symphytum preparations.

In-Silico UHPLC Method Optimization for Aglycones in the Herbal Laxatives Aloe barbadensis Mill., Cassia angustifolia Vahl Pods, Rhamnus frangula L. Bark, Rhamnus purshianus DC. Bark, and Rheum palmatum L. Roots.

For the European Pharmacopoeia (Ph. Eur.) herbal monograph draft of Cassia angustifolia Vahl. and Cassia senna L. leaves and pods, a safety limitation of aloe-emodin and rhein was proposed, due to toxicological concerns. A quantitative, analytical method of the anthraquinone aglycones in all Ph. Eur. monographed herbal laxatives is of interest. A rational method development for the aglycones aloe-emodin, rhein, emodin, chrysophanol, and physcion in five herbal drugs was realized by using 3D chromatographic modelling (temperature, solvent, and gradient time) and design of experiment (DOE) software (DryLab® 4). A methodical approach suitable for the challenging peak tracking in the chromatograms of the herbal drugs in dependence on the changes in the chromatographic conditions is described by using a combination of mass spectroscopy (MS) data (UHPLC-QDa), UV/Vis-spectra, and peak areas. The model results indicate a low robust range and showed that with the selected chromatographic system, small interferences could not be averted. The separation achieved shows a pure UV/Vis spectrum for all aglycones except for chrysophanol in Aloe barbadensis and emodin in Cassia angustifolia fruit. A gradient with the best resolution of the aglycones in all five drugs is proposed, and its suitability demonstrated for the quantification of aglycones in these herbal drugs.

Is excessive electroencephalography beta activity associated with delinquent behavior in men with attention-deficit hyperactivity disorder symptomatology?

BACKGROUND/AIMS: The attention-deficit/hyperactivity disorder (ADHD) shows an increased prevalence in delinquents compared to the normal population. In recent studies, a subgroup of subjects with ADHD as well as a subgroup of delinquents displayed excessive electroencephalography (EEG) beta activity, which has been associated with antisocial behavior in ADHD children. We investigated whether delinquent behavior in adults with ADHD symptomatology is related to excessive beta activity. METHODS: We compared the resting state EEGs (eyes open/closed) of delinquent and nondelinquent subjects with ADHD symptoms and those of a control group regarding EEG power spectra and topography. RESULTS: Delinquents with ADHD symptomatology showed more beta power at frontal, central and parietal brain regions than nondelinquents with ADHD symptoms. CONCLUSION: Excessive beta power may thus represent a risk factor for delinquent behavior in adults with ADHD symptomatology. The awareness of such a risk factor may be helpful in the assessment of the risk for delinquent behavior in a psychiatric context and may provide a neurobiological background for therapeutic interventions.

Function and activity in patients with knee arthroplasty: validity and reliability of a German version of the Lysholm Score and the Tegner Activity Scale.

OBJECTIVE: The Lysholm score and the Tegner activity scale are widely used for assessing knee function and activity level after knee ligament injuries. This study aimed to asses validity and reliability of the German versions of the Lysholm score (Lysholm-G) and the Tegner activity scale (Tegner-G) in patients after total knee arthroplasty (TKA). METHODS: Two patient groups (<3 months postoperative; 3 to 12 months postoperative) and a healthy control group completed both questionnaires twice within 3 to 7 days. On the first occasion, the SF-12 questionnaire was also administered. The instruments' absolute and relative reliability, internal consistency, construct validity (discriminative validity and exploratory factor analysis), criterion validity, and floor/ceiling effects were determined. RESULTS: Both instruments showed acceptable relative reliability (Lysholm-G: ICC2,1 = 0.87; Tegner-G: ICC2,1 = 0.79), and the Lysholm-G had a Cronbach's alpha of 0.93. Kruskal-Wallis test and post-hoc Mann-Whitney U tests showed significant differences in both scores among the groups. Factor analysis of Lysholm-G yielded three factors that together explained 76% of the variance. Correlations between the Lysholm-G/Tegner-G and the physical component of the SF-12 were moderate (ρ = 0.60/0.59). Item analysis of the Lysholm-G revealed a low relative reliability for the item "instability" and low discriminative validity for the items "locking" and "instability". CONCLUSIONS: This study demonstrated acceptable psychometric performances for the Lysholm-G and the Tegner-G scales as outcome measures for patients with TKA. A short version of the Lysholm score without the "locking" and "instability" items might be more appropriate for TKA patients.

Neurophysiological correlates of delinquent behaviour in adult subjects with ADHD.

The attention deficit/hyperactivity disorder (ADHD) shows an increased prevalence in arrested offenders compared to the normal population. The aim of the present study was to investigate whether ADHD symptoms are a major risk factor for criminal behaviour, or whether further deficits, mainly abnormalities in emotion-processing, have to be considered as important additional factors that promote delinquency in the presence of ADHD symptomatology. Event related potentials (ERPs) of 13 non-delinquent and 13 delinquent subjects with ADHD and 13 controls were compared using a modified visual Go/Nogo continuous performance task (VCPT) and a newly developed version of the visual CPT that additionally requires emotional evaluation (ECPT). ERPs were analyzed regarding their topographies and Global Field Power (GFP). Offenders with ADHD differed from non-delinquent subjects with ADHD in the ERPs representing higher-order visual processing of objects and faces (N170) and facial affect (P200), and in late monitoring and evaluative functions (LPC) of behavioural response inhibition. Concerning neural activity thought to reflect the allocation of neural resources and cognitive processing capability (P300 Go), response inhibition (P300 Nogo), and attention/expectancy (CNV), deviances were observable in both ADHD groups and may thus be attributed to ADHD rather than to delinquency. In conclusion, ADHD symptomatology may be a risk factor for delinquency, since some neural information processing deficits found in ADHD seemed to be even more pronounced in offenders with ADHD. However, our results suggest additional risk factors consisting of deviant higher-order visual processing, especially of facial affect, as well as abnormalities in monitoring and evaluative functions of response inhibition.

Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription.

Poly(ADP-ribose) polymerase-1 (PARP-1) and nuclear factor kappaB (NF-kappaB) have both been demonstrated to play a pathophysiological role in a number of inflammatory disorders. We recently presented evidence that PARP-1 can act as a promoter-specific coactivator of NF-kappaB in vivo independent of its enzymatic activity. PARP-1 directly interacts with p300 and both subunits of NF-kappaB (p65 and p50) and synergistically coactivates NF-kappaB-dependent transcription. Here we show that PARP-1 is acetylated in vivo at specific lysine residues by p300/CREB-binding protein upon stimulation. Furthermore, acetylation of PARP-1 at these residues is required for the interaction of PARP-1 with p50 and synergistic coactivation of NF-kappaB by p300 and the Mediator complex in response to inflammatory stimuli. PARP-1 physically interacts with the Mediator. Interestingly, PARP-1 interacts in vivo with histone deacetylases (HDACs) 1-3 but not with HDACs 4-6 and might be deacetylated in vivo by HDACs 1-3. Thus, acetylation of PARP-1 by p300/CREB-binding protein plays an important regulatory role in NF-kappaB-dependent gene activation by enhancing its functional interaction with p300 and the Mediator complex.

Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression.

Nuclear factor kappaB (NF-kappaB) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. Here, we show that coactivator-associated arginine methyltransferase CARM1/PRMT4 is a novel transcriptional coactivator of NF-kappaB and functions as a promoter-specific regulator of NF-kappaB recruitment to chromatin. Carm1 knockout cells showed impaired expression of a subset of NF-kappaB-dependent genes upon TNFalpha or LPS stimulation. CARM1 forms a complex with p300 and NF-kappaB in vivo and interacts directly with the NF-kappaB subunit p65 in vitro. CARM1 seems to act in a gene-specific manner mainly by enhancing NF-kappaB recruitment to cognate sites. Moreover, CARM1 synergistically coactivates NF-kappaB-mediated transactivation, in concert with the transcriptional coactivators p300/CREB-binding protein and the p160 family of steroid receptor coactivators. For at least a subset of CARM1-dependent NF-kappaB target genes, the enzymatic activities of both CARM1 and p300 are necessary for the observed synergy between CARM1 and p300. Our results suggest that the cooperative action between protein arginine methyltransferases and protein lysine acetyltransferases regulates NF-kappaB-dependent gene activation in vivo.