Decrease In Anxiety By Inhibiting Glyoxalase I (Additional Reason For Pau D'arco)

[Lejeboca]

Mostly the role of glyoxalase I (GloI) inhibition in cancer therapy has been discussed on RP. The paper below shows its role for decreasing anxiety.

Earlier posts (see, e.g., Cottage Cheese & Fresh Flax Seed Oil Cures Cancer and Is Pau D'Arco Really The Best Option Out Of The Tabebuia Buffet?) and the entire thread on lapachone state that pau d'arco (Tabebuia spp.) is the best natural GloI inhibitor. Along come chinese skullcap (scutellaria baicalensis) and curcumin (Curcuma longa) .

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Abstract: Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in mice; however, its role in anxiety is controversial, and the underlying mechanism is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels of methylglyoxal (MG), a GABAA receptor agonist. Mice overexpressing Glo1 on a Tg bacterial artificial chromosome displayed increased anxiety-like behavior and reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety-like behavior, while higher doses caused locomotor depression, ataxia, and hypothermia, which are characteristic effects of GABAA receptor activation. Consistent with these data, we found that physiological concentrations of MG selectively activated GABAA receptors in primary neurons. These data indicate that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABAA receptor activation. More broadly, our findings potentially link metabolic state, neuronal inhibitory tone, and behavior. Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders.

 

[bdawg]

Good find! any more research related to the Glo1 pathway of anxiety reduction?

 

[olive]

Pair Pau D’Arco with L-Threonine.

L-Threonine creates methylglyoxal, a polyamine inhibitor.
Lapachone, found in Pau D’Arco, is a glyoxalase l inhibitor which stops methylglyoxal created by l-threonine being destroyed and turned into lactic acid.

 

[bdawg]

I did some quick research.

Lapachol seems to have some toxic/anti-fertility anti embryo effects

Is it a case of look at the net positive? otherwise this herb seems very promising

 

[Lejeboca]

Here is a paper by the same group, in part, as in my original posting. This paper continues the above work and shows that the effects of Glo1 lowering drugs on GABA have no adverse side effects of other types of drugs and are not only along the anxiety axis but also along the depression one. The effect on the depression is not typically seen by the "standard" GABA drugs.

GLO1 inhibitors for neuropsychiatric and anti-epileptic drug development

Many current pharmacological treatments for neuropsychiatric disorders, such as anxiety and depression, are limited by a delayed onset of therapeutic effect, adverse side effects, abuse potential or lack of effect in many patients. These off-target effects ...

www.ncbi.nlm.nih.gov

Abstract:
Many current pharmacological treatments for neuropsychiatric disorders, such as anxiety and depression,
are limited by a delayed onset of therapeutic effect, adverse side effects, abuse potential or lack of efficacy
in many patients. These off-target effects highlight the need to identify novel mechanisms and targets
for treatment. Recently, modulation of Glo1 (glyoxalase I) activity was shown to regulate anxiety-like
behaviour and seizure-susceptibility in mice. These effects are likely to be mediated through the regulation
of MG (methylglyoxal) by Glo1, as MG acts as a competitive partial agonist at GABA A (γ -aminobutyric acid
A) receptors. Thus modulation of MG by Glo1 represents a novel target for treatment. In the present article,
we evaluate the therapeutic potential of indirectly modulating MG concentrations through Glo1 inhibitors
for the treatment of neuropsychiatric disorders.

In pp. 463--464, Using the TST, Benton et al. [9] reported a positive
correlation between Glo1 expression and depression-like
behaviour in mice. This observation appears surprising in the
light of the link between Glo1, MG and GABA, since no other
GABA A R agonists (e.g. barbiturates and benzodiazepines)
reduce immobility on the TST [46]. Although Glo1 inhibitors
have not been evaluated for their efficacy in depression-
like behaviours, these data suggest that Glo1 inhibition may
have antidepressant activity, probably by increasing MG
levels.