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Rationale for Mushroom Nutrition Supplementation in Neurodegenerative Conditions*

by Carolin Cornelius, Monia Cavallaro, Maria Scuto and Vittorio Calabrese(more info)

listed in neurological, originally published in issue 208 - August 2013

Rationale

The effects of edible mushrooms is an area of increasing interest associated with health benefits in a number of pathologies, mostly associated with oxidative stress and free-radical-induced cell damage(1).

Hericium Mushrooms
Hericium Mushrooms

Neurodegenerative Processes

The brain has a large potential oxidative capacity but a limited ability to counteract oxidative stress (2-4). Within the cell, reactive oxygen species (ROS) are physiologically present at minimal concentration as by-products of aerobic metabolism as well as second messengers in many signal transduction pathways and, in normal conditions, there is a steady-state balance between pro-oxidants and antioxidants which is necessary to ensure optimal efficiency of antioxidant defences (5-8).

However, when the rate of free radical generation exceeds the capacity of antioxidant defences, oxidative stress ensues with consequential severe damage to DNA, proteins and lipids(9-11). Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain, including neurodegenerative disorders such as Alzheimer’s disease (AD)(12-16). Recently the term “nitrosative stress” has been used to indicate the cellular damage elicited by nitric oxide and occurs when intermediates are produced from nitrosate thiol, hydroxyl and amine groups as well as its congeners peroxynitrite N2O3, nitroxyl anion and nitrosonium (all can be indicated as reactive nitrogen species or RNS) (17-19).

There is growing evidence that the continuous presence of a small stimulus such as low concentrations of ROS is in fact able to induce the expression of antioxidant enzymes and other defence mechanisms. The basis for this phenomenon may be encompassed by the concept of hormesis (21), a term for generally-favourable biological responses to low exposures to toxins and other stressors and which can be characterized as a particular dose–response relationship in which a low dose of a substance is stimulatory and a high dose is inhibitory. In this context, radicals may be considered to be beneficial since they act as signals to enhance defences rather than deleterious as they are when cells are exposed to high levels of ROS.

On the other hand, oxidants, when in excess can, over long term, disrupt redox homeostasis, impose oxidative stress and subsequently lead to a dramatic loss of molecular fidelity which is the major cause for accumulation of unfolded or misfolded proteins in brain cells. Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases, but also amyotrophic lateral sclerosis and Friedreich ataxia belong to the so called “protein conformational diseases” and affect several millions of aged people in all the world (20).

Cells have evolved mechanisms such as the unfolded protein response, where chaperons can rescue misfolded proteins by breaking up aggregates and assisting the refolding process, while proteins thatcannot be rescued by refolding are delivered to the proteasome by other chaperones to be recycled(22). In general, an unfolded protein response conformational diseases are conditions that arise from the dysfunctional aggregation of proteins in non-native conformations. This often is associated with multiple metabolic derangements that result in the excessive production of ROS and oxidative stress (22).

The ability of a cell to deal with ROS and RNS requires the activation of pro-survival pathways as well as the production of molecules endowed with anti-oxidant and anti-apoptotic activities.

It is plausible to exploit the possibility that mushroom nutrition can activate signaling processes within brain cells leading to augmented cellular stress resistance, thereby opening novel therapeutic windows to withstand deleterious effects of oxidative damage in vulnerable neurons and consequently cell death-mediated degenerative diseases (23-45).

It has been known that enzyme therapy plays an important role in several clinical conditions such as in cancer treatment, malignant lymphoma and cardiovascular disorders(46,47). All the above evidence supports the notion that nutritional approaches with mushroom biomass can be a novel target for preventive medicine actions based on the modulation of endogenous redox state to withstand conditions of oxidative stress which is the main pathogenic factor operating in aging and neurodegenerative disorders, as well as in the promotion and progression of malignant cells.

Accordingly, a variety of proteins have been isolated and characterized from mushrooms and fungi including lectins, ribonucleases, ribosome-inactivating proteins, anti-fungal proteins, laccases and ubiquitin-like peptides Some of these proteins exhibit anti-proliferative/anti-tumour, anti-microbial and human immunodeficiency virus (HIV)-1 reverse transcriptase (RT) inhibitory activities(48). These mushroom enzymes mentioned below are thought to prevent oxidative stress as well as to inhibit cell growth in several diseases.

In view of recent findings showing that mushrooms are effective in the treatment of oxidative stress, we have determined the levels of various enzymes associated with the removal of ROS (superoxide dismutase, catalase, peroxidase, GSH-reductase, NADPH-cytochrome C reductase, laccase) as well as tyrosinase and in the following mushrooms: Polyporus umbellatus, Agaricus blazei, Pleurotus ostreatus and Hericium erinaceus.

Method

Antioxidant enzyme activities in these select mushrooms were investigated by simulating the intestinal tract of the human body with the following proteolytic enzymes:

1.Pepsin (500 IU/tablet) at pH 2 for 30 min. at 37ºC in an incubator with orbital shaking

2.Trypsin (500 IU/tablet) at pH 7.6 for 30 min. at 37ºC in an incubator with orbital shaking.

Results

It was found the following:

Table 1 Enzyme Activity in presence of Proteolytic Enzymes (U /500 mg Biomass)*

TABLE 1

Polyporus umbellatus

Agaricus blazei

Pleurotus ostreatus

Hericium erinaceus

Superoxide dismutase

(SOD)

11.8 10³ U

143.5 10³ U

13.043 10³ U

19.430 10³ U

Superoxide dismutase (SOD) + Pepsin

10.4 10³ U

115.9 10³ U

10,671 10³ U

17,544 10³ U

Superoxide dismutase (SOD) + Trypsin

11.1 10³ U

128.7 10³ U

11,940 10³ U

14.961 10³ U

NADPH Cyt. “P-450” reductase

10,200 uM

7,500 Um

8,330 uM

4,620 uM

NADPHCyt. “P-450” reductase + Pepsin

10,800 uM

4,725 uM

4,957 uM

2,772 uM

NADPH Cyt. “P-450” reductase + Trypsin

11,000 uM

7,510 uM

3,716 uM

5,108 uM

GSH Reductase

15,4 U

510 U

69.6 U

21.74 U

GSH Reductase + Pepsin

4,3 U

84 U

6.9 U

20.9 U

GSH Reductase + Trypsin

13.55 U

517 U

18.55 U

21.80 U

 * Mycology Research Laboratories Ltd supplied the biomass samples of Agaricus blazei, Pleurotus ostreatus , Polyporus umbellatus and the Hericium erinaceus for the study. (www.mycologyresearch.com )

1. Highest levels of superoxide dismutase (SOD) (Tables 1,2) were recorded in Hericium erinaceus and Pleurotus ostreatus (19,430x103 U/500g biomass and 13,043x103 U/500g biomass, respectively), followed by Agaricus blazei (143.5x103 U/500g biomass) and Polyporus umbellatus (11.8x103 U/500g biomass). Incubation with pepsin induced a 10 to 20% decrease in enzyme activity, while trypsin decreased by 6-10%, in all species examined but Hericium erinaceus where the decrease was 20%.

2. NADPH-Cyt P450 reductase activity (Tables 1,2) was detected in all four mushroom species with Polyporus umbellatus exhibiting the highest activity (10,2 mU/500g biomass), followed by Pleurotus ostreatus (8,33 mU/500g biomass), Agaricus blazei (7,5 mU/500g biomass) and Hericium erinaceus (4,62 mU/500g biomass. In the presence of proteolytic enzymes, enzyme activity was decreased by 40% after pepsin treatment in Agaricus blazei, Pleurotus ostreatus and Hericium erinaceus. No change in the activity was found in Polyporus umbellatus. Interestingly under trypsin exposure only Pleurotus ostreatus showed a 50% reduction in the enzyme activity while in the other mushrooms no changes were measured.

3. Reduced glutathione, most commonly called glutathione or GSH, is a relatively small molecule ubiquitous in living systems. Significant levels of GSH reductase activity were measured Agaricus blazei (510 U/500g biomass), Pleurotus ostreatus (69.6 U/500g biomass) and Hericium erinaceus (21.74 U/500g biomass), with the lowest activity found in Polyporus umbellatus (15.4 U/500g biomass) (Tables 1,2). In the condition of the intestinal tract no change in the activity in Hericium erinaceus was detected under pepsin. However it was found a significant reduction of 70-80% under pepsin in Agaricus blazei, Pleurotus ostreatus and Polyporus umbellatus. With regards to trypsin effects no reduction of the enzyme activity was measured in Hericium erinaceus as well as in Agaricus blazei. Polyporus umbellatus showed a 12% reduction and Pleirozus ostreatus 34% decrease (Tables 1,2).4)

Conclusions

In conclusion, these studies suggest that important antioxidant and cytoprotective enzymes are present in all the different fungi examined, suggesting considerable potential for therapeutic strategies based on nutritional interventions with mushrooms to limit and/or prevent the adverse consequences associated with free-radical induced damage in neurodegenerative disorders.

*This article is a synopsis of two articles published in the Clinical Journal of Mycology Vol II. July 2009: http://www.mycologyresearch.com/pdf/newsletter/Clinical_Journal_of_Mycology_Vol2_July2009.pdf

  1. Mushroom Nutrition as a Target for Novel Therapeutic Strategies: Relevance to Nutritional Approaches and Antioxidant Redox Mondulation in Antiaging Medicine. Calabrese V.1, Cornelius C.1, Cavallaro M.1, Cambria M.1, Toscano MA2
  2. Comparative Enzyme Analysis of Polyporus umbellatus, Agaricus blazei , Pleurotus osteratus and Hericium erinaceus. Cornelius C.1, Cavallaro M.1, Cambria M.T.1 Toscano M.A.2 and Calabrese V.1

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About Carolin Cornelius, Monia Cavallaro, Maria Scuto and Vittorio Calabrese

Carolin Cornelius, Monia Cavallaro, Maria Scuto and Vittorio Calabrese, Department of Chemistry and Biomedical Sciences, Faculty of Medicine, University of Catania, 95100 Catania, Italy. They may be contacted via calabres@unict.it

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