Antidepressant potential of Agaricus Bisporus: A comprehensive study

 Corresponding author: Tilotma Sahu. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Antidepressant potential of Agaricus Bisporus: A comprehensive study Tilak Kumar Sinha, Tilotma Sahu * and Rajesh Kumar Nema Rungta Institute of Pharmaceutical Sciences, Bhilai, Durg C.G, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 Publication history: Received on 09 December 2024; revised on 21 January 2025; accepted on 24 January 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.1.0076 Abstract Many important nutrients and medicinal bioactive chemicals are thought to be possible to be found in mushrooms. Agaricus Bisporus is the most significant commercially grown mushroom worldwide and a member of the Basidiomycetes family. Rich in minerals, vitamins, lipids, fiber, proteins, and carbohydrates, this mushroom is a wellknown nutritious food. Mirtazapine is a commonly prescribed antidepressant medication that is a member of the BCS Class II drug class and has high permeability and low solubility. Goal: The formulation of the gastroretentive floating tablets of mirtazapine was statistically optimized using the Box Behnken design. Materials and Procedures: Using design expert software, a polynomial model was created after the responses were examined using the three components of the three design levels. A comparison was made between three distinct independent components. Reviewing contemporary research on the nutritional and therapeutic qualities of Agaricus Bisporus is the primary aim of this research. Only findings released after 2006 have been taken into consideration due to the acceleration of mushroom research during the past 10 years. The maintenance of human health has relied heavily on the use of therapeutic substances derived from plants and fungi from ancient times. Natural products are the source of more than half of all contemporary clinical medications and are crucial to pharmaceutical industry drug research initiatives. A significant natural food and medicinal source is mushrooms. The significance of edible and wild mushrooms was recognized by traditional Aboriginal people, and these are currently being examined for their bioactivity in treating a range of illnesses. This review's objective is to provide a concise scientific explanation of the pharmacognosy, chemistry, and pharmacology of button mushrooms. Keywords: Agaricus Bisporus; Antidepressant; Nutrition; Mushroom; Button Mushroom 1. Introduction Globally, mushrooms are already a significant component of human diets as non-animal sources of protein, but less is known about their environmental impact and value chain. A controlled drug delivery system is utilized to improve a medicine's therapeutic efficacy and get around some issues with traditional therapy (1). A member of the kingdom's Agaricaceae family, division Basidiomycota of fungi, Agaricus Bisporus Imbach is one of the most widely grown mushrooms around the world. Champignon, button, and white mushrooms are some of the common names for this species. In this essay, the word "mushroom" will be used instead. Apart from its medicinal and cosmetic uses, this fungus is primarily consumed by humans. It is extremely nutritious because it is a source of (2). The agent must be delivered to the target tissue in the ideal quantity at the ideal timing in order to achieve optimum therapeutic efficacy, resulting in low toxicity and few adverse effects. Delivering a medicinal ingredient to the target site in a prolonged controlled release form can be accomplished in a number of ways.Microspheres are tiny spherical particles that usually have dimensions between 1 μm and 1000 μm, which is in the micrometer range. Microspheres can also be called microparticles. A variety of synthetic and natural materials are used to make it. Commercially available microspheres come in three varieties: glass, polymer, and ceramic (3). in order to create microspheres using a variety of natural and artificial materials. Commercially available microspheres come in three varieties: glass, polymer, and ceramic. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 605 Polyethylene microspheres are frequently utilized as either temporary or permanent fillers (4). Polyethylene microspheres can form porous structures in ceramics and other materials because of their lower melting temperature. Many important nutrients and medicinal bioactive chemicals are thought to be possible to be found in mushrooms. Agaricus Bisporus is the most significant commercially grown mushroom worldwide and a member of the Basidiomycetes family. This mushroom is a well-known, healthful food because of its abundance of minerals, vitamins, fiber, lipids, proteins, and carbohydrates (5). These mushrooms are known being hepatoprotective, antioxidant, antimicrobial, anticancer, antidiabetic, antihypercholesterolemic, and antihypertensive properties. They contain a number of active ingredients, including essential amino acids, peptides, glycoproteins, polysaccharides, lipopolysaccharides, triterpenoids, nucleosides, lectins, fatty acids, and their derivatives. Reviewing contemporary research on the nutritional and therapeutic qualities of Agaricus Bisporus is the main goal of this study (6). Material – Agaricus Bisporus collect from local market, Methanol Figure 1 Agaricus Bisporus 1.1. Plant profile Table 1 Botanical Discription Botanical name Agaricus Bisporus (Lange) Imbach Kingdom Fungi Divison Basidomycota Class Agaricomycetes Order Agaricales Family Agaricaceae Genus Agaricus Species Agaricus Bisporus 1.1.1. History and ethnopharmacology The basidiomycete fungus that can be eaten A. Bisporus In indigenous to North American and European grasslands. Often referred to as WBM, or white button mushroom it is extensively grown in the majority of nations and makes up the majority of every mushroom eaten in Australia and The United States. It was first grown in France, according to historical records, and cultivar strains came from Western Europe(7). Only the pharaohs were considered deserving of eating perhaps even touching mushrooms, as the ancient Egyptians thought They may grant immortality. They were able They were able to provide immortality mushrooms. frequently known as "food for the gods" in the ancient Rome. Folklore in Mexico, China, Russia, and other nations claimed that mushrooms gave people supernatural power (8). 1.1.2. Historical review of medicinal plant The most prevalent species in the fungus kingdom, which includes edible mushrooms, is Agaricus. Up to 38% of the world's mushroom production comes from the genus Agaricus, which includes both species A. bisporus (such as button, Swiss brown with portobello variations) and species Agaricus campestris (such as field mushroom).One Flammulina World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 606 filiformis, or enoki), oysters (Ostreatus Pleurotus), shiitake (Lentinus edulis), Tricholoma murrillianum, or matsutake, and porcini (Boletus edulis) are further edible mushrooms (9). Face and neck erythema was recorded. She experienced tightness in her chest, tongue angioedema, and urticaria. This led to more intramuscular adrenaline (500 mg), which improved her condition. A chest radiograph was normal, and an ECG revealed atrial fibrillation without ischemic alterations. Four hours after experiencing acute symptoms, The tryptase level of the patient was increased at 24.8 mg/L(reference range < 11.5 mg/L). After being admitted to the ward for the night, she was discharged the next day after being weaked off of oxygen (10). 1.1.3. Historical sources relevant for study of medicinal plants The edible basidiomycete mushroom A. bisporus is indigenous to North American and European grasslands. Often referred to as white button mushroom (WBM), it is extensively grown in the majority of nations and makes up the majority of all mushrooms consumed in Australia and the US. It was first grown in France, according to historical records, and cultivar strains came from Western Europe. The pharaohs were the only ones considered deserving of eating perhaps even touching mushrooms, as the ancient Egyptians thought They may grant immortality. Mushrooms were frequently Known as "food for the gods" in classical Rome (11).The free form of iron in mushrooms makes up onethird of their content. Their polysaccharide content successfully fights HIV and is utilized as an anticancer medication. The mushrooms' biologically active chemicals have been utilized as insecticides and nematodes and have antifungal, antibacterial, antioxidant, and antiviral qualities.Studies have shown that women who regularly consume these button mushrooms are less likely to get breast cancer (12). 1.1.4. Phytoconstituent Given that A. bisporus is classified as a dish that is good for people health and contains high levels of dietary fiber, antioxidants, and vitamins like thiamine, vitamin and ascorbic acid D2, in addition to minerals like folates, ergothioneine (ET), as well as polyphenol that could be beneficial for cardiovascular and diabetic conditions, it is possible that The anti-inflammatory properties of the mushroom, hypoglycemic, as well as low cholesterol properties . Together with ergosterol, tocopherols, linoleic acid, and lectins, β-glucans make up around half of the bulk of the fungal cell wall (13). The primary aromatic component of mushrooms is agaritine and its derivatives, which are chemically classified as hydrazines. Certain types of mushrooms, such as A. bisporus, contain hydrazines. Agaritine has been shown to contribute to the creation of damaging aryl diazonium ions. In mushrooms, gamma-glutaminyl-4-hydroxybenzene is the main phenolic component(14). Table 2 The components of Agaricus Bisporus CONSTITUENT (UNIT/100 G) REFERENCES PROXIMATE H20 92.45 Gram (15) ENERGY 22 KCAL (16) PROTEIN 93 KJ (17) ADJUSTED PROTEIN 3.09 G (18) TOTAL LIPID 2.18 G (19) ASH 0.34 G (20) CARBOHYDRATE 0.85 G (21) FIBER 3.26 G (22) SUGAR 1.98 G (23) GLUCOSE 1.48 G (24) FRUCTOSE 0.17 G (25) FIBER 1 G (26) World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 607 Table 3 The microelements that Agaricus Bisporus contains MICROELEMENT VALUE/(UNIT/100 G) REFERENCES Calcium (Ca) 3 mg (27) Iron (Fe) 0.5 mg (28) Magnesium (Mg) 9 mg (29) Phosphorus (P) 86 mg (30) Potassium (K) 318 mg (31) Sodium (Na) 5 mg (32) Zinc (Zn) 0.52 mg (33) Copper (Cu) 0.318 mg (27) Manganese (Mn) 0.047 mg (28) Selenium (Se) 9.3 µg (25) Table 4 Agaricus Bisporus contains vitamins. Vitamins Value/(unit/100 g) Refereces Vitamin C,total ascorbic acid 2.1 mg (34) Thiamin 0.081 mg (20) Riboflavin 0.402 mg (23) Niacin 3.607 mg (21) Pantothenic acid 1.497 mg (35) Vitamin B6 0.104 mg (36) Folate 17 µg (37) Choline b17.3 mg (38) Betaine 9.4 mg (39) Vitamin B12 0.04 µg (22) Tocopherol, beta 0.01 mg (26) Tocopherol, gamma 0.01 mg (40) Tocopherol, delta 0.01 mg (41) Vitamin D (D2 + D3 ) 0.2 µg (42) Vitamin D2 (ergocalciferol) 0.2 µg (43) 2. Medicinal importance of Agaricus Bisporus In order to create functional foods, there is growing interest in removing the bioactive components from mushrooms. The use of A. bisporus in numerous traditional medicines has a long history. Extracts from A. bisporus and/or the bioactive substances it contains are being used more and more globally as anti-cancer agents, antioxidants, and antiinflammatory substances to treat a range of human diseases, such as cancer, diabetes, fungal and bacterial infections, immune system problems,and coronary heart disease (44). 2.1. Anti cancer One of the mostdeadly illnesses in the world is cancer. Polysaccharides and other natural active components from mushrooms have recently been isolated and shown to have strong anti-cancer effects against a variety of cancer cell World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 608 lines. The glucan and other polysaccharides found in basidiomycota are thought to have therapeutic properties. The beta-glucan family of chemicals includes the polysaccharides, which seem to have anti-tumorigenic properties through boosting cellular immunity (45). α-glucan, β-glucan, and galactomannan are the three primary polysaccharides found in A. bisporus with galactomannan accounting for 55.8% of the total . According to, (1→3) and (1→6)-d-glucans are the most frequently extracted glucans from A. bisporus 69% more tumor necrosis factor (TNFα) was produced when Juice from fruits enhanced with A. bisporus α-glucans (5 g glucans/day) ingested lipopolysaccharide (42). 2.2. Antidiabetic The three main polysaccharides present in A. bisporus are Galactomannan, α-glucan, and β-glucan, with galactomannan making up 55.8% of the total. The most often isolated glucans from A. bisporus are (1→3) and Consuming fruit juice supplemented with α-glucans from A. bisporus (5 g glucans/day) and (1→6)-d-glucans Lipopolysaccharide resulted in a 69% increase in tumor necrosis factor (TNFα) (46). Adults at risk for type 2 diabetes may benefit from frequent use of A. bisporus over time due to its many components, which have possible health benefits of antioxidants and antiinflammatory. indicated that consuming Agaricus Bisporus could be a useful method for postmenopausal women to prevent nonalcoholic fatty liver disease's stage of liver steatosis that can be reversed early (47). 2.3. Antioxidant Numerous writers have documented A. bisporus's total phenolics and antioxidant qualities. In comparison to Lentinula edodes, Pleurotus Grifola frondosa, Pleurotus eryngii, and Ostreatus, A. bisporus mushrooms, particularly port abellas (A. bisporus brown ), had a greater capacity for antioxidants (48). Phenolic chemicals are said to be the primary antioxidant components present in mushrooms. There is a strong correlation between phenolic contents and antioxidant activity, indicating that phenolic compounds may be the main source of antioxidant activity in edible. On the other hand, although having a low level of antioxidant activity, A. bisporus exhibits significant levels of phenolics compound (40). “One of the main risk factors for the development of atherosclerosis” one of the most dangerous diseases in humans, and subsequent cardiovascular Illness is hyperlipidemia, which is distinguished by high triglyceride levels or cholesterol (Esmaillzadeh or Azatbakth, 2008). Because phytosterols inhibit the absorption of cholesterol, they can lower LDL and plasma cholesterol (49). 2.4. Antihyperlipidemic Increased triglyceride or cholesterol levels, or hyperlipidemia, are a major risk factor for the the beginning and development of atherosclerosis, one of the most dangerous illnesses in humans, and consequent cardiovascular disease (50). As a hypolipidemic agent, lovastatin lowers cholesterol in people with hypercholesterolemia, lowering their risk of cardiovascular disease.shown that the triple-negative breast cancer cell line MDA-MB-231 responds to lovastatin's anti-cancer actio The cell line for triple-negative breast cancer MDA-MB-231 reacts to the anti-cancer effects of lovastatin . asserted that 565.4 mg/kg of Agaricus Bisporus of lovastatin and proposed that A. bisporus, the white button mushroom, lowers serum and/or liver cholesterol levels (46). 2.5. Antimicrobial According to certain earlier research, A. bisporus extracts made with methyl alcohol demonstrated antibacterial properties against a variety of bacteria, yeasts, and dermatophytes. Extracts from A. bisporus have been shown to exhibit microbial inhibition (51). As seen in Figure 1, AgNPs, or silver nanoparticles are among most widely employed Nanoparticles of metal and have strong antibacterial and antifungal properties. It is believed that Agaricus Bisporus plays a significant Role in the creation of AgNPs, or silver nanoparticles; it was shown that A. bisporus ranked second (by roughly 11%) in the synthesis of significant nanoparticles, behind the oyster mushroom Pleurotus sp (52). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 609 Figure 2 Biosynthesis silver Nanoparticles Using Mushroom Agaricus Bisporus 2.6. Anticholesterlomic and antiglycemic Examining the theory that consumption of WBM fruiting bodies controls antiglycemic reactions was the aim of this investigation. Rats were given a hypercholesterolemic diet for these investigations, and streptozotocin injections caused type 2 diabetes in the rats for three weeks (25). Oral administration of ABP for four weeks significantly reduced plasma TC and LDL in hypercholesterolemic rats, leading to the conclusion that A bisporus exhibited both hypoglycemic and hypolipidemic effects on rats (53). 2.7. Anti inflammatory activity The anti-inflammatory qualities were tested using activated macrophages. of A. bisporus methanolic excerpts , and it was discovered that certain edible mushroom species may have anti-inflammatory properties in vitro (54). 3. Improved dendritic cell maturation from bone marrow This study investigated how A. bisporus supplementation affected the maturation of bone marrow-derived dendritic cells in C57BL mice in vitro (BMDC) and discovered that the manifestation of maturation indicators CD40, CD80, CD86, and major histocompatibility complex-II increased dose-dependently (49). 3.1. Skin disorders This study's objective was to investigate how isolated A. bisporus tyrosinase affected B16F10 melanocytes' ability to produce melanin by inhibiting pigment cell machinery. It was demonstrated using B16F10 melanocytes that pure tyrosinase stimulates melanogenesis because it increases tyrosinase absorption. Purified tyrosinase enhanced melanin concentration and cellular tyrosinase activity in B16F10 melanocytes in a way that is depending on dosage. Based on the results, pure tyrosinase may be utilized as a potential therapy for vitiligous skin conditions (55). 3.2. Antinociceptive properties Komura et al. demonstrated the anti-inflammatory and antinociceptive properties of mannogalactans, fucogalactans, and fucomannogalactans that were separated from A. bisporus var. hortensis and Agaricus brasiliensis (56). 3.3. Agaricus Bisporus as nanoparicles The methanolic nanoparticles of A. bisporus have various advantages to treat cancer, viral, bacterial, fungal diseases, etc, Because there are so many fruiting bodies generated worldwide, this kind of nanoparticle synthesis by edible and medicinal mushrooms is both economical and appropriate for use in nanomedicine (37). As a saprotrophic decomposer of leaf litter, the basidiomycete A. bisporus naturally influences the carbon cycle in terrestrial habitats (57). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 610 3.4. Future prospect Based on a variety of components found in A. bisporus, emerging data from fascinating new research indicates that mushrooms may also help to increase energy, reduce fatigue and balance the effects of stress, support healthy skin and hair, cleanse the liver and flush out toxins, enhance brain cell function, and promote memory and concentration (58). 4. Mechanism of action • Neurotransmitter modulation Neurotransmitters implicated in mood regulation, including serotonin, dopamine, and norepinephrine, may be affected by L-lysine in terms of their levels and activity (59). • Stress reduction by modifying the hypothalamic-pituitary-adrenal (HPA) axis, L-lysine may help lower anxiety and stress (60). • Antioxidant activity Due to its antioxidant qualities, L-lysine may help shield the brain from inflammation and oxidative damage (61). 5. Biochemical pathway • SEROTONIN PATHWAY The production of serotonin, a neurotransmitter that controls mood, hunger, and sleep, involves L-lysine (62) • Dopamine and Norepinephrine Regulation Dopamine and norepinephrine are neurotransmitters that are essential for motivation and mood management, and L-lysine may have an impact on their function (63). • GABA and Glutamate Regulation L-lysine may also affect the activity of two neurotransmitters involved in mood regulation: glutamate (an excitatory neurotransmitter) and GABA (an inhibitory neurotransmitter) (64). Figure 3 Biochemical Pathway 6. Clinical evidence • Reduced Symptoms of Depression: L-lysine supplementation has been demonstrated to lessen depressive symptoms, such as elevated mood, decreased anxiety, and improved cognitive performance (65). • Anxiolytic Effects: In both human and animal research, L-lysine has been shown to have anxiolytic (antianxiety) properties (66). • Antidepressant Effects: Studies on animals have demonstrated that L-lysine has antidepressant properties, and some human research indicates that it might also have antidepressant properties (67). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 611 7. Animal studies • Decreased stress and anxiety: Studies on mice and rats have demonstrated that L-lysine supplementation reduces stress and anxiety behaviors (68). • Better mood: In animal models, L-lysine has been shown to elevate mood and lessen Depressieve model (69). Figure 4 Rat on Antidepressant 7.1. Safety and interaction • Safety: Although large dosages of L-lysine may result in gastrointestinal adverse effects, it is usually regarded as safe for intake (70). • Interactions: Blood thinners, diabetic drugs, and immunosuppressants are among the drugs that L-lysine may interact with (71). 7.1.1. Future prospect Based on a number of components found in A. bisporus, it appears that mushrooms may also help to: increase energy, reduce fatigue and balance the effects of stress, support healthy skin and hair, cleanse the liver and flush out toxins, enhance brain cell function, and improve memory and concentration. Table 5 Patent on Agaricus Bisporus S no. Patent Number Title Description Assignee Filling Date 1 US10893921B2 Pharmaceutical composition containing Agaricus Bisporus extract Treating cancer and immune-related disorders MycoMed Technologies Inc. 202001-17 2 EP3647797A1 Medicinal mushroom extract and uses thereof Treating various diseases, including cancer, diabetes, and neurodegenerative disorders Agaricus Biosciences LLC 202007-22 3 WO2020121015A1 Agaricus Bisporus-based composition for treating inflammatory diseases Treating inflammatory diseases, such as arthritis and asthma Korea University Research and Business Foundation | 202004-23 4 CN112345191B Agaricus Bisporus polysaccharide and its Antitumor therapy Sichuan University 202005-19 World Journal of Biology Pharmacy and Health Sciences, 2025, 21(01), 604-615 612 application in antitumor therapy 5 JP2020515111A Agaricus Bisporus extract and its use in treating dementia Treating dementia Hokkaido University 202002-20 6 JP2021522121A Agaricus Bisporus extract and its use in treating skin diseases Treating skin diseases, such as acne and psoriasis Hokkaido University 202101-28 7 CN113456921B Agaricus Bisporus polysaccharide and its application in immunotherapy Immunotherapy Sichuan University 202012-15 8. Conclusion Because of its high nutritional content, a bisporus may offer substantial protection against malnutrition, particularly in developing and underdeveloped nations. Although A. bisporus has medicinal properties, especially as an antioxidant, antibacterial, anticancer, and anti-cardiovascular disease agent, however it is not good for your diet. In recent decades, edible mushrooms have gained popularity as a source of medication or as an addition to health foods. This adage is appropriate for mushrooms because of their amazing therapeutic food, medicine, and mineral properties. They are therefore a great advantage for human welfare. In the future, A. bisporus may be employed to treat a variety of illnesses and serve as a vital component or backbone of research. Compliance with ethical standards Disclosure of conflict of interest No conflict of interest to be disclosed. References [1] Goglio P, Ponsioen T, Carrasco J, Milenkovi I, Kiwala L, Van Mierlo K, Helmes R, Tei F, Oosterkamp E, Pérez M. An environmental assessment of Agaricus Bisporus ((JE Lange) Imbach) mushroom production systems across Europe. European Journal of Agronomy. 2024 Apr 1; 155:127108. [2] Pérez-Bassart Z, Reyes A, Martínez-Abad A, López-Rubio A, Fabra MJ. Feasibility of Agaricus Bisporus waste biomass to develop biodegradable food packaging materials. Food Hydrocolloids. 2023 Sep 1; 142:108861. [3] Andrade, M. S., Ishikawa, O. H., Costa, R. S., Seixas, M. V. S., Rodrigues, R. C. L. B., & Moura, E. A. B. (2022). Development of sustainable food packaging material based on biodegradable polymer reinforced with cellulose nanocrystals. Food Packaging and Shelf Life, 31, Article 100807. [4] Goglio P, Ponsioen T, Carrasco J, Milenkovi I, Kiwala L, Van Mierlo K, Helmes R, Tei F, Oosterkamp E, Pérez M. An environmental assessment of Agaricus Bisporus ((JE Lange) Imbach) mushroom production systems across Europe. European Journal of Agronomy. 2024 Apr 1; 155:127108. [5] Ali SB, Smith W. Agaricus Bisporus mushroom anaphylaxis: A case report and review of the literature. Journal of Allergy and Clinical Immunology: Global. 2024 Nov 1;3(4):100324. [6] Koivikko A, Savolainen J. Mushroom allergy. Allergy 1988; 43:1-10. [7] Bhushan A, Kulshreshtha M. The medicinal mushroom Agaricus Bisporus: review of phytopharmacology and potential role in the treatment of various diseases. Journal of Nature and Science of Medicine. 2018 Jan 1;1(1):49. [8] Andersson HC, Gry J. Phenyl Hydrazines in the Cultivated Mushroom Agaricus Bisporus Occurrence, Biological Properties, Risk Assessment and Recommendations. Nordic Council of Ministers, Copenhagen. Tema Nord 558, Ekspressen Tryk & Kopicenter; 2004. p. 1-123.