The Medicinal Mushroom Agaricus bisporus

Review of Phytopharmacology and Potential Role in the Treatment of Various Diseases

Abstract

Nature has been a source of medicinal agents for thousands of years and an impressive number of modern drugs have been isolated from natural sources, based on their use in traditional medicine. Since ancient time's plants as well as fungus sources of medicinal compounds have continued to play a dominant role in maintenance of human health. Over 50% of all modern clinical drugs are of natural product origin and play an important role in drug development programs in the pharmaceutical industry. Mushrooms are an important natural source of food and medicine. Traditional aboriginals knew the importance of edible and wild mushrooms, and these are now being screened for their bioactivity in various ailments. We are aiming for this review is to compact a compressive scientific description of pharmacognosy, chemistry, and pharmacology of button mushroom (Agaricus bisporus), depending on published data and other available resources.

INTRODUCTION

The world population is increasing day-by-day. Currently, it is considered nearly 7 billion. Some theories suggest that by the year 2050, the global population will reach to 9 billion, and during 2100, it could be 20 billion.[¹] Lack of food and deterioration in human health will be burning issue due to the population growth and urbanization, with a concomitant reduction in arable land. To address global food demand (especially protein) can be converted into lingo-cellulosic agricultural and forest residues into protein-rich mushrooms is one of the most economically viable and sustainable biotechnology processes.[²] Utilization of edible fungi to fulfil human nutritional rights has been a common denominator in the history of humankind.[³⁴] Penicillin, perhaps the most famous of all antibiotic drugs, is derived from a common fungus called Penicillium. Many other fungi also produce antibiotic substances, which are now widely used to control diseases in human and animal populations. The discovery of antibiotics revolutionized healthcare worldwide. Some fungi which parasitize caterpillars have also been conventionally used as medicines.[⁵]

Agaricus bisporus (A. bisporus) Imbach is the most wild and cultivated edible mushroom and represents more than 40% of the world bearing of mushrooms.[⁶⁷] It is cultivated in over 70 countries and on every ascetic, except Antarctica. The global production in the 1990s was more than $800 million/year[⁸] and increased to $12,250 in 2002 (UN 2010). A. bisporus has a luscious taste with more nutritional value has very good aroma or flavoring taste is used as food and in food industries.[⁹] It is considered to have high biological activity, low toxicity and has significance folklore and ethanopharmacological significance. Apart from food and food beverages it has a role in perfumery, cosmetic industries and pharmaceutical industries.[¹⁰¹¹] Wild A. bisporus were referred for customer due to their flavor and texture.[¹²] It has been reported lots of primary and secondary metabolites responsible for the therapeutic activity for the prevention and treatment of many diseases such as cancer, hyperlipidemia, microbial diseases, cardiovascular problems, liver diseases, and immune problems. A. bisporus is a litter degrading basidiomycete commonly found in humic-rich environments which are useful as a model organism and cultivated in large scale for the food industry. Due to its ecological niche, it produces a variety of enzymes for detoxification and degradation of humified plant litter.[¹³]

HISTORY AND ETHNOPHARMACOLOGY

A. bisporus is an edible basidiomycete mushroom native to grasslands in Europe and North America. Commonly known as white button mushroom (WBM), is widely cultivated in most countries and it constitutes the bulk of all mushrooms consumed in the United States and Australia. Historical evidence indicates that it was first cultivated in France and that cultivar strains originated in Western Europe.[¹⁴¹⁵¹⁶] Ancient Egyptians believed mushrooms could grant immortality and thus, only the pharaohs were deemed worthy of eating or even touching them. In ancient Rome, mushrooms were often referred to as “food for the gods.” In Russia, China, and Mexico, and other world cultures, folklore held that mushrooms conferred superhuman strength.[¹⁷] Conventionally, the fungus was used in the treatment of cancer, cerebral stroke, and heart diseases. Furthermore, it has anti-aging property.[¹⁸] They represent as one of the world's greatest untapped resources of nutrition and palatable food of the future. Mushrooms have been found to be more effective against cancer, cholesterol reduction, stress, insomnia, asthma, allergies, and diabetes.[¹⁹] They can be used to bridge the protein malnutrition gap because they have a high amount of protein. Mushrooms are useful to increase the immunity. Hence, it provides a nutrient supplement as a form of tablets. They are also useful for diabetic and patients with cardiovascular disorders (because they contain low starch and low cholesterol). One-third of the iron in the mushrooms is available in free form. Their polysaccharide content is used as an anticancer drug and combat HIV effectively.[²⁰²¹] Biologically active compounds from the mushrooms possess antifungal, antibacterial, antioxidant, and antiviral properties, and have been used as insecticides and nematicides as well. There have been studies that demonstrate that women who eat these button mushrooms daily have reduced chances of getting breast cancer. The mushrooms can be thought to inhibit the production of enzymes that affect the production of estrogen which is a hormone that causes cancer to develop. The special effects of this substance on other kinds of cancer are still being studied.[²²]

BOTONICS

Botanical name: Agaricus bisporus (Lange) Imbach [Figure 1]

Figure 1: Morphology of Agaricus bisporus

Kingdom - Fungi

Divison - Basidomycota

Class - Agaricomycetes

Order - Agaricales

Family - Agaricaceae

Genus - Agaricus

Species - Agaricus bisporus[¹⁷]

A young fungus either light-yellow or light-brown in color with an abutted cap, known as common mushroom, white mushroom or button mushroom. In strains with darker flesh, the premature mushroom is variously marketed as cremini mushroom, baby bella, Mini bella, roman mushroom, Italian mushroom or brown mushroom.[²³] Original cap is a pale gray-brown, with extensive, horizontal scales on a paler background and fading toward the margins. It is first hemispherical in shape before flattening out with maturity and 5–10 cm (2–4 inches) in diameter. The precise, crowded gills are free and initially pink, then red-brown and finally a dark brown with a whitish edge from the cheilocystidia. The cylindrical stipe is up to 6 cm tall by 1-2 cm wide and bears a thick and narrow ring, which may be streaked on the upper side. The firm flesh is white, although stains a pale pinkish-red on bruising. The spore print is dark brown. The spores are oval to round and measure approximately 4.5–5.5 × 5–7.5 μm. Mushrooms are considered as a heterotrophic and have no chlorophyll.[²⁴] Scientific confession of the commercial cultivation of A. bisporous was made by French botanist Joseph Pitton de Tournefort in 1707.[²⁵] French agriculturist Olivier de Serres seen that transplanting mushroom mycelia would lead to the propagation of more mushrooms. Originally, cultivation was capricious as mushroom growers would watch for good flushes of mushrooms in fields before digging up the mycelium and replanting them in beds of composted manure or inoculating “bricks” of compressed litter, loam, and manure. Spawn collected this way usually contained pathogens and commonly crops would be infected or not grow at all.[²⁶] In 1893, pure culture, spawn was discovered and produced by the Pasteur Institute in Paris, for cultivation on composted horse dung.[²⁷] The substrate for culturing A. bisporous is the most complicated culture medium used for edible mushroom production. The compost is prepared by a two-stage mechanism. In the first stage, a mixture of raw materials, animal manure (such as stable bedding or poultry manure) and gypsum are assembled, wetted and formed into a stack (windrow). The cultivation of this species have succeeded on different composted organic such as chicken, horse or pigeon manures, straw residues from wheat, oat, tifton,[²⁸] reed crops,[²⁹³⁰] corn cob, molasses, wheat bran,[³¹] sugarcane bagasse, tea levaves,[³²] brachiaria,[³³] reed plant (Phragmites australis) straw,[³⁴] water hyacinth (Eichhornia crassipes),[³⁵] and others. Wheat straw with waste tea leaves[³⁶³⁷] and waste paper was used in the casing layer.[³⁸] Water inclusion is controlled, and the stack is dissembled and reformed at intervals. In the second stage, pasteurization is done to brace the compost for a selective growth medium on which A. bisporus has been inoculated. This two-phase process for substrate preparation has some demerits, Such as more time and space required for cultivation.[^39404142] Automated harvesting of A. bisporous by machine at the laboratory level; and the resulting pilot harvester was completely tested on a commercial mushroom farm. The apparatus associates various handling systems and mechatronic technologies. Mushrooms are located and sized using image analysis and a monochromatic vision system. An expert selection algorithm then decides the order in which they should be picked and selection of picking action (bend, twist or both).[⁴³⁴⁴] One of a pair of suction cup mechanisms attached to the single head of a Cartesian robot is then deployed, which can delicately detach individual mushrooms and place them gently into a specially designed, compliant finger conveyer. After high-speed skiving, a gripper mechanism is finally used to remove mushrooms from the conveyor into packs at the side of the machine.[⁴⁵]

CHEMICAL CONSTITUENTS

A. bisporus comes under the category of a food which is beneficial for humane health with excellent levels of dietary fibers and antioxidants including vitamins namely; thiamine, ascorbic acid, vitamin D₂ etc as well as minerals like folates, ergothioneine (ET) and polyphenols which may provide favorable effects on cardiovascular diseases and diabetes suggests that the mushroom might have potential anti-inflammatory, hypoglycemic, and hypocholesterolemic effects.[^46474849] Around half of the fungal cell wall mass is constituted by β-glucans along with ergosterol, tocopherols, linoleic acid, and lectins. Fungus contains 1-6 mg of phenolics/g of dried mushroom and flavonoid concentrations ranged between 0.9 and 3.0 mg/g of dried matter; as myricetin and catechin.[⁵⁰] Agaritine and its derivatives which chemically belongs to hydrazines, are the main aromatic compound of mushrooms. Hydrazines are present in mushroom species like A. bisporus, etc., Agaritine was found to contribute to the formation of toxic aryl diazonium ions. Gamma-glutaminyl-4-hydroxybenzene is the principal phenolic compound present in mushrooms.[⁵¹⁵²]

Abou-Heilah et al. reported potassium and sodium concentration was 300 and 28.2 parts per million, respectively.[⁵³] The ash analysis revealed the high amount of K, P, Cu, and Fe.[⁵⁴]A. bisporus contains Ca (0.04 g), Mg (0.16 g), P (0.75 g), Fe (7.8 g), Cu (9.4 mg), Mn (0.833 mg) and Zn (8.6 mg) per kilogram fresh weight.[⁵⁵] Various constituents, microelements, and vitamins present which is shown in [Tables 123].[⁵⁶]

Table 1: Constituents present in Agaricus bisporus

Table 2: Microelements present in Agaricus bisporus

Table 3: Vitamins present in Agaricus bisporus

PHARMACOLOGICAL ACTIVITY

Antioxidant and immunomodulating activity

Polysaccharides reported in A. bisporus had a good amount of “a” and “b” glucans which was confirmed by Fourier-transform infrared spectroscopy (FTIR) and were found to have immune stimulating effect.[⁵⁷]

Metabolic effect

A total of 240 seven-day old mix sexes quail chicks were randomly allocated to four experimental groups treated with the A. bisporus then old male and female chicks were separated at 21 days. Birds were allowed to free to take water and feed at the time of the 35 days of the growth period. Total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were found to be significantly decreased compared to the control. HDL cholesterol was significantly increased with 2% mushroom compared to the control so in conclusion 2% mushroom positively affects cholesterol, TG, high-density lipoprotein (HDL), and LDL of quails diet.[⁵⁸]

Anticancer activity

A. bisporus is effective in case of breast cancer because it decreases aromatase enzyme activity and estrogen biosynthesis. The researcher evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive and found to have decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line.[⁵⁹]

Anticholesterolemic and antiglycemic

The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates antiglycemic responses. For these studies the rats were fed hypercholesterolemic diet and type 2 diabetes induced by injection of streptozotocin for 3 weeks in rats. The result allowed reduced plasma glucose, TG concentrations, liver enzyme activities, alanine aminotransferase and aspartate aminotransferase.[⁶⁰] In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma TC, LDL, and concluded that A bisporus had both hypoglycemic and hypolipidemic activity in rats.[⁶⁰]

Anti-inflammatory activity

The anti-inflammatory activity of methanolic extracts of A. bisporus was investigated on activated macrophages and found that some edible mushrooms species have a potential anti-infl amatory capacity in vitro.[⁶¹]

Biomarkers of inflammation

In such a study (pilot) evaluation of bioavailability of ET in healthy men (n = 10), using a randomized, cross-over, dose-response, postprandial time-course design, conducted at the General Clinical Research Center at Pennsylvania State University in 2009. ET was administered with mushroom powder. Postprandial red blood cell concentrations of ET and plasma glucose, TGs, HDL, LDL and TC were also monitored. Biomarkers of inflammation and oxidative stress were evaluated using C-reactive protein and oxygen radical absorbance capacity (total). ET from A. bisporus mushrooms is bioavailable as assessed using red blood cell uptake postprandial, and consumption is associated with an attenuated postprandial TG response.[⁶²]

Enhances maturation of bone marrow-derived dendritic cells

In this study, in vitro supplementation with A. bisporus on the maturation of bone marrow-derived dendritic cell (BMDC) of C57BL mice and found that dose-dependently increased expression of maturation markers CD40, CD80, CD86, and major histocompatibility complex-II.[⁶³]

As a source of antibiotics and in cosmetics industry

A. bisporus contain a group of benzoquinone which belongs to antibiotics group and tyrosinase enzyme which was isolated from this species is completely resemble human tyrosinase which is very beneficial in field of cosmetics.[⁶⁴]

Intestinal fermentation

Kawakami et al., reported the intestinal fermentation of A. bisporus in rats. It was proved by physical examination of animals by bacterial and HPLC analysis of cecal content and concluded that the mushrooms powder have a beneficial effect on the intestine.[⁶⁵]

Skin disorders

This investigation was based on an effect of purified tyrosinase from A. bisporus on B16F10 melanocytes for the melanin production through blocking pigment cell machinery. Using B16F10 melanocytes showed that the stimulation of melanogenesis by purified tyrosinase is due to increased tyrosinase absorption. Cellular tyrosinase activity and melanin content in B16F10 melanocytes were increased by purified tyrosinase in a dose-dependent manner. The results indicated that purified tyrosinase can be treated as a contestant for the treatment of vitiligous skin conditions.[⁶⁶]

Antinociceptive properties

Komura et al. proved the anti-inflammatory and antinociceptive effects of fucogalactans, fucomannogalactans, and mannogalactans isolated from Agaricus brasiliensis and A. bisporus var. hortensis.[⁶⁷]

Antimicrobial activity

The study involved isolating Erwinia spp. and Ralstonia solanacearum from infected plants followed by subjecting the isolates and commercially acquired Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Streptococcus pneumoniae (ATCC 49617), Proteus vulgaris (ATCC 49990), Candida albicans, Aspergillus niger (ATCC 1015), Fusarium oxysporum (ATCC 16608), Ustilago maydis (ATCC 14826), Microsporum gypseum (ATCC 15621), and Malassezia furfur (ATCC 14423) and were successfully antagonized by mushroom.[⁶⁸]

Agaricus bisporus as nanoparticles

Owaid et al., developed the methanolic nanoparticles of A. bisporus have various advantages to treat cancer, viral, bacterial, fungal diseases, etc., This type of the nanoparticle synthesis by edible and medicinal mushrooms are economic and suitable to apply in nanomedicine due to the huge number of fruiting bodies which are produced in the world.[⁶⁹⁷⁰⁷¹] The commercial mushroom production process is usually performed in buildings or tunnels under highly controlled environmental conditions. In nature, the basidiomycete A. bisporus has a significant impact on the carbon cycle in terrestrial ecosystems as a saprotrophic decayer of leaf litter.[⁷²]

FUTURE PROSPECTS

Emerging evidence from exciting new studies suggests that mushrooms may also help to: boost energy, eliminate fatigue and balance the effects of stress, promote healthy skin and hair, cleanse the liver and flush out toxins, improve brain cell function and promote memory and concentration on the basis of various constituents present in the A. bisporus.

CONCLUSION

We can conclude about the diverse benefits of mushrooms towards humans by the words of the father of medicine that is, Hippocrates “Let food be your medicine and medicine be your food.” This saying applies suits mushrooms, as they have tremendous medicinal food, drug, and mineral values. Hence, they are a valuable asset for the welfare of humans. A. bisporus may be used to cure various diseases in future and play a key role or like a backbone in the research field. They are small plants but treasures major qualities which act as a key principle for various researches applicable to pharmacology, pharmacognosy, microbiology and biotechnology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

The author would like to express his hearty thanks Mrs. Garima A Tiwari, Sr. Assistant Professor, Department of Pharmacy, BBD University for necessary corrections and advises; Central Drug Research Institute, Lucknow for providing library facilities to access the journals and books and made this review possible.