Acute and Chronic Mental Stress Both Influence Levels of Neurotransmitter Precursor Amino Acids and Derived Biogenic Amines.

Acute and chronic mental stress are both linked to somatic and psychiatric morbidity, however, the neurobiological pathways of these associations are still not fully elucidated. Mental stress is known to be immunomodulatory, which is one of the basic concepts of psychoneuroimmunology. In the present study, neurotransmitter precursor amino acid levels and derived biogenic amines were analyzed prior to and at 0, 30 and 60 minutes following an acute mental stress test (with/without chronic mental stress) in 53 healthy subjects. Psychometric measurements of mental stress, depression and anxiety were collected. Kynurenine/tryptophan was influenced by the factor acute mental stress (KYN/TRP increase), no influence of the factor chronic mental stress or any interaction was found. Phenylalanine/tyrosine was influenced by the factor acute mental stress (PHE/TYR increase) as well as by chronic mental stress (PHE/TYR decrease). Interactions were not significant. KYN/TRP correlated with state anxiety values, while PHE/TYR correlated negatively with chronic stress parameters. Kynurenic acid was significantly reduced in the acute and quinolinic acid in the chronic mental stress condition. In conclusion, neurotransmitter precursor amino acid levels and derived biogenic amines are influenced by acute and chronic mental stress. Mechanisms beyond direct immunological responses may be relevant for the modulation of neurotransmitter metabolism such as effects on enzyme function through cofactor availability or stress hormones.

Leoligin, the major lignan from Edelweiss, inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase and reduces cholesterol levels in ApoE-/- mice.

The health benefit through the control of lipid levels in hyperlipidaemic individuals is evident from a large number of studies. The pharmacological options to achieve this goal shall be as specific and personalized as the reasons for and co-factors of hyperlipidaemia. It was the goal of this study to reveal the impact of leoligin on cholesterol levels and to define its mechanism of action. Oral application of leoligin in ApoE-/- mice led to significantly reduced total serum cholesterol levels and a reduction in postprandial blood glucose peak levels. In the absence of biochemical signs of toxicity, leoligin treatment resulted in reduced weight gain in mice. The effects of leoligin on serum cholesterol levels may be due to a direct inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) by a unique, non-statin-like binding mode. Postprandial serum glucose peaks may be reduced by a mild peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity of leoligin. No effect on atherosclerotic plaque size was observed. As a non-toxic, cholesterol-, peak glucose-, and weight gain-lowering compound, leoligin continues to fulfil characteristics of a potential agent for the treatment of cardiovascular disease (CVD). The counterregulatory overexpression of hepatic HMGCR in leoligin treated animals possibly explains the missing permanent anti-atherosclerotic effect.