Medicinal Plant, St John's Wort, May Reduce Neuronal Degeneration Caused By Parkinson's Disease

In the last few years, the idea that the excessive numbers of free radicals has an important role in the complex etiology of Parkinson's disease has spread. Post-mortem investigations have revealed evidence of lipid peroxidation as well as oxidative damage to the DNA of brain proteins in patients suffering from the disease. The increase of oxidative stress is attributed, among other factors, to a less active mitochondrial complex I. Certain environmental contaminants such as pesticides, and in particular Rotenone, can cause Parkinson's. Nevertheless, the mechanism that causes Rotenone to have these effects is not yet fully understood. The hypothesis is that the increase in the production of Reactive oxygen species (ROS) caused by the altered function of the mitochondrial complex I could be the cause of the degeneration of dopaminergic neurons through the apoptotic process.

A proposition that is widely accepted is that ingesting high quantities of antioxidants can reduce the risk of suffering from Parkinson's disease or delay its progression. Natural products are highly appreciated in the development of drugs for their great structural diversity and wide range of pharmacological effects. Approximately one third of the best selling drugs in the world are, or derive from, natural substances. With this is mind, a plant well known for its antidepressant effects, St John's wort (Hypericum perforatum), was chosen for an in vivo test using a model of Parkinson's disease with rotenone.

St John's wort presents proven antioxidant effects, which make it beneficial for all those pathologies that cause an increase of free radicals. With the goal of determining which component of St John's wort is responsible for its beneficial role against neurodegenerative diseases, it was decided to evaluate the effects of a standard Hypericum Perforatum extract with a 0.3% concentration of Hypericin, versus those of an extract with 11% Hyperforin but deficient in other active compounds of the plant. In the same experimental conditions as both these extracts, Quercetin was used as a positive control.

Body weight was controlled to determine whether or not the use of the different drugs had any significant impact on it. The pre-treatment of animals with both types of extract reduced the negative effects of Rotenone, as well as the loss of body weight during the chronic treatment. The obtained results after the catalepsy test show that the pre-treatment of animals with both extracts reduced the latency period increased by Rotenone. These behavioural alterations suggest that neurons in the nigrostriatal pathway are sensitive to the toxic effects of the pesticide. In fact, the administration of the toxin for a period of 30 days caused extensive lesions to that region, in many cases creating areas with missing neurons. The evaluation of neuron degeneration caused in the substantia nigra shows a reduction of dopaminergic neuron death with St John's wort.

The evaluation of antioxidant enzymes levels, superoxide dismutases, catalase, and glutathione peroxidase, conclude that administration both St John's wort extracts can prevent the increase of the three enzymes, reducing them significantly. St John's wort reduces the exacerbated production of Reactive oxygen species produced in the presence of Rotenone, as well as the damage that the free radicals cause dopaminergic neurons in the substantia nigra, avoiding the action of apoptosis. The neuron protecting effects are greater with the standard Hypericum Perforatum extract with the 0.3% concentration of Hypericin. This implies that the powerful antioxidant effects of the plant is caused by a synergic action of various of its active compounds.

The research team formed by Mª Ángeles Gómez del Rio, Irene Iglesias Peinado and Juana Benedí González, from the Departamento de Farmacología; Mª Isabel Sánchez Reus, from the Departamento de Bioquímica y Biología Molecular of the Facultad de Farmacia at the UCM has been awarded the CINFA 2008 prize (Real Academia Nacional de Farmacia) for their investigation.