Open access peer-reviewed chapter

Mushroom; Chemistry, Bioactive Components, and Application

Written By

Ahmed M. Saad, Mahmoud Z. Sitohy, Belal A. Omar, Mohamed T. El-Saadony and Basel Sitohy

Submitted: 26 February 2022 Reviewed: 02 March 2022 Published: 13 June 2022

DOI: 10.5772/intechopen.104182

From the Edited Volume

Current Topics in Functional Food

Edited by Naofumi Shiomi and Anna Savitskaya

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Abstract

Apposite energy is required for body activity. Energy is derived from the oxidation of various biomolecules like carbohydrates, lipids, and proteins. These bio-molecules in the proper amount are essential for the structural and functional activities of any living being. Certain vitamins and enzymes are also needed for the maintenance of biochemical processes. Our daily food is the major source of these biomolecules. From the last few decades, researchers have placed giant effort into searching for a food material that can provide nearly all the essential components required to maintain the energy need and consequently, balancing the body’s homeostasis. Mushrooms have the potential to address the above-raised issues. Besides their pleasant flavor and culinary value, mushrooms are an important source of biomolecules that include large macromolecules (protein, carbohydrate, lipid, and nucleic acid) as well as small molecules (primary metabolites, secondary metabolites, and natural products). This chapter discusses the bioactive compounds in edible mushroom and their activities.

Keywords

  • mushroom
  • species
  • bioactive components
  • anticancer
  • antidiabetic

1. Introduction

Mushrooms are a group of fungi with a distinctive fruiting body that can be either epigeous or hypogenous and large enough to be seen with the naked eye and picked by hand [1]. They are either saprophytic, parasitic or mycorrhizal. Out of these three categories, the majority of them are saprophytic and they play an important role in the biodegradation and bioremediation of recalcitrant substances [2]. Notably, there are about 14,000 mushroom species that have been reported to date and a further 126,000 species more are yet to be discovered [3]. The majority of mushroom species are edible and over 400 species are poisonous [4]. Out of these more than 2000 edible species, 5–6 species are grown on a mass scale, 40 species are produced commercially and 80 species are cultivated experimentally (Figure 1). Edible mushrooms have very minimal calorie value as they contain less amounts fat and carbohydrate and are also cholesterol-free. In addition, edible mushrooms are rich in other vital nutrients like niacin, vitamin D, proteins, selenium, potassium, riboflavin. Mushrooms also contain a significant amount of fiber which helps in the appropriate digestion of food (Table 1) [1]. The active compounds in common mushrooms and the nutritional value of these mushrooms and their activities were showed in Table 2 and Figure 2.

Figure 1.

Mushroom species based on their uses.

MushroomMedicinal valueProtein (g/100 g)Carbo (g/100 g)Lipid (g/100 g)Fibers (g/100 g)References
ClitocybeneAnticancer8.11–12.1864.47–77.121.14–2.04[5]
CordycepsAnti-asthma21.924.28.2[6]
HericiumAntihypercholesterolic22.357.03.57.8[7]
TrametesAntidiabetic[8]
Lentinusimmunomodulator26.365.12.3[8]
HypsizygusAnticancer19.6–21.065–68.54.0–5.6[8]
FlammulinaImmunomodulator, anti-asthma,Antihypercholesterolic3.9–17.886–70.81.8–2.9[9]
Grifolaantidiabetic, anti- arthritic, anti-viral, anti- obesity anticancer, anti- osteoporosis,21.158.83.110.1[8, 9]
Agaricusanticancer, immunomodulator, hepatoprotective, anti- viral, antimutagenicm antidiabetic, antihyperchlosterolic56.337.52.7[10]
PhellinusAntidiabetic, hepatoprotective, Immunomodulator6.11–10.975.04–83.820.96–15.86[11]
Ganodermaantiviral, antithrombotic, hepatoprotective, anti- osteoporosis, anticancer, hypoglycemic, anti- aging, antiallergenic, hypocholesterolemic, antimutagenic,13.382.33.0[12]
Pleurotushepatoprotective, antitumor, anticancer, antiviral, antioxidant, antibacterial, antidiabetic, anti- arthritic, anti-obesity17–4237–480.5–524–31[13]
TricholomaAntihypercholesterolic18.1–30.531.1–52.32–6.630.1[14]
SarcodonaAnti- aging1264.62.85.1[15, 16]
LeucopaxillusAnticancer[15, 16]
TremellaAnticancer, antidiabitic40.694.80.21.4[15, 16]

Table 1.

Nutritional values of edible mushrooms and their activities.

MushroomCommon nameBioactive compounds/ingredientsHealth benefit
Tremella fuciformisSnow Mushroompropanediol, glycerin, arganiaspinosa (argan) kernel oil, seawater, sodium hyaluronate, sodium PCA, sodium lactate, 3-O-ethyl ascorbic acid, pentylene glycol, caprylyl glycol, N-prolylpalmitoyl tripeptide-56 acetate, hydroxyethylcellulose, polyglyceryl-4 caprate, diheptyl succinate, capryloylglycerin/sebacic acid copolymer, sodium carbomer, ethylhexylglycerinSkin health
Agaricus blazeiOrivedavr>27% beta-glucanAnti-hyperglycemic,
AgaricusblazeiMurrill>0.90% polyphenolsantihypercholestromic
extract
Ganoderma lucidumReishi Elixir MixOrganic Reishi mushroom extract (1500 mg), 18 mg of vitamin c, tulsi, organic mintSupport the body’s sleep
cycles as well as
support
occasional stress
L. edodesShiitake Goldcapsules15% Lentinan 60% PolysaccharidesFor immune system,
cardiovascular health,
skin and muscle health
support, anti-bacterial properties
Ganoderma lucidumReishiMax capsules13% Polysaccharides (beta-1,3-glucans) and 6% triterpenes (ganoderic acids and others) nucleosides, fatty acids (oleic acid), and amino acids, Gelatin, Stearic acidAntidiabetic
Cordyceps sinensisCordycepsextractcapsulesAmino acids, including L-tryptophan, ergosterol, polysaccharides (β-glucans)Control blood glucose levels
Ganoderma lucidumGANOHERB ReishiOrganic ganoderma spore powder and extract- balanced blood sugar level diabetes (non-GMO & gluten-free), 100% natural, 400 mg/capsulesSupports healthy glucose metabolism, blood purification, and healthy blood sugar levels
mushroom
bitter melon
Ganoderma lucidumPure red reishicapsules>9.40% triterpenesBoost immune system And antidiabetic attribute Levels of blood sugar balanced
organic reishitablets>16% beta-glucan
>1.80% polyphenols
Pleurotus eryngii,GlucoSANO-Diabetes,Agaricusblazei, ErgoD2VR
Agaricus blazei,Health Formula(enriched pleurotuseryngii),
Hypsizyguswhite beech, brown beech,
tessellates,cordycepsmilitaris, vitamin
Cordyceps militarisD2 (ergocalciferol),
vegetable capsules,
myceliated whole oats, rice
flour, silica
Ganoderma lucidumGanoUltraGanoSuperMycelium, primordia,Anticancerous, anti-stress,
fruitbodies, andantidiabetic
extracellular compounds
vegetarian capsule
(pullulan), 100% organic
white milo
(growing substrate)
Lentinus edodes, GrifolaAgarikon.1750 mg of high-quality solubleAnticancer attributes
frondosa,polysaccharides per table
Ganoderma lucidum,
Pleurotus ostreatus
and Agaricus blazei
Hericium erinaceusAmyloban 3399Fruiting body extract, AmycenoneVR, Standardized to contain amyloban including hericenones 1950 mgBrain health
super lion’s mane
(tablets)
Ganoderma lucidumGanoderma herbal,Extract, polysaccharidesBoost immunity,
antidiabetic capsulesantidiabetic
Ganoderma lucidum,E & Rose Wellness’Powdered extract, selenium, copper, B vitamins, vitamin D, as well as prebiotics, polysaccharidesStress relief, liver & brain health, concentrations/ focus, brain & immune health, immune health, endurance, stamina & endurance, immune health, blood sugar & blood pressure control.
Cordyceps sinensis,Magic Milk
Grifola frondosa,
Inonotus obliquus,
Hericium erinaceus

Table 2.

Bioactive components in common mushroom.

Figure 2.

Diverse application of elidable mushrooms.

Oxidative stress (OS) is one of the major causes of any disease such as neurodegenerative (NDs), cardiovascular (CDs) and reproductive diseases (RDs), and diabetes [17]. Inflammation is the progressive result of the severe burden of OS. Any biomolecules with anti-oxidative and anti-inflammatory activity show a better response in the treatment of the above diseases [18]. The polyphenols, terpenoids, alkaloids, and other important biomolecules found in edible mushrooms prove their efficacy in therapeutics with minimal side effects [19]. Mushrooms and their biomolecules are known to have been used to cure diabetes by Indian and Chinese patents from ancient times [20]. The active components in these mushroom species; Ganoderma lucidum, Lentinus edodes, Pleurotus ostreatus, Pleurotus sajor-caju, Grifola frondosa, Poriacocos, have exhibited potent anti-diabetic activity [21]. For example, the polysaccharides derived from Pleurotus ostreatus exhibits potent antidiabetic activity in the streptozotocin-persuaded Diabetic Rat model [22]. β-glucans and several other biomolecules present in edible mushrooms show strong anti-diabetic activity [23]. Recently the edible oyster mushroom Pleurotus fossulatus aqueous extract improved liver and kidney function in the streptozotocin-induced diabetic rats, besides reducing blood glucose levels, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) [24].

Disorders related to the heart and blood vessels are grouped into cardiovascular diseases (CVDs) [25]. Mushrooms and their bioactive components can prevent CVDs [26]. Being functional foods, edible mushrooms contain a significant number of bioactive compounds that show strong potential in the treatment of CVDs [27]. The antioxidant and anti- inflammatory biomolecules present in mushrooms reduce the atherosclerosis risk which is directly related to CVDs [28]. Diseases related to the reproductive systems are very common now a day. Abnormalities in the endocrine system are mainly responsible for the progression of reproductive diseases (RDs). Several RDs like reproductive tract infections, prostate cancer, breast cancer, ovarian cancer, etc. are most common in different populations [29]. Mushrooms and their bioactive molecules show anti-tumor activity which can be immensely beneficial in the treatment of different RDs. RDs commonly lead to different types of cancer and several biomolecules present in edible mushrooms can prevent metastasis toward cancer [1, 26]. Neurodegenerative diseases (NDs) like Huntington’s disease (HD), Alzheimer’s disease (AD), and Parkinson’s disease (PD), etc. have been effectively treated by edible mushrooms through their bioactive components [30]. Progression of the NDs is the main cause of death which can be significantly inhibited by the biomolecules present in edible mushrooms [31]. Polyphenols, alkaloids, and several other biomolecules in edible mushrooms prove their efficacy in the treatment of different neurodegenerative diseases [32]. Similarly, a different form of cancer can also be treated by the biomolecules found in edible mushrooms [23]. This review discusses the role of mushrooms and their biomolecules to be utilized for the treatment of some most common diseases like CVDs, RDs, NDs, diabetes, and the different forms of cancer.

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2. Mushroom active compounds against cardiovascular diseases (CVDs)

Cardio Vascular Diseases (CVDs) are a category of heart and blood diseases, including coronary heart disease, cerebrovascular disease, rheumatic heart disease, and other diseases. CVDs are the leading cause of death worldwide. In the past few decades, researchers have shown the use of mushrooms and their bioactive compounds as therapeutic agents for CVDs. In 2010, Guillamon et al. reported the potentially positive effects of mushroom consumption on risk markers for CVDs and identified some potential bioactive compounds responsible for their therapeutic activity. Several studies have shown the influence of mushroom intake on some metabolic markers (total low-density lipoproteins (LDL), high-density lipoproteins (HDL): cholesterol, fasting triacylglycerol, homocysteine, blood pressure) which could potentially reduce the risk of cardiovascular disease. Relevant nutritional aspects of mushrooms include high fiber content, low-fat content, and low trans isomers of unsaturated fatty acids. Mushrooms also have low sodium concentrations and other significant components, such as eritadenine, phenolic compounds, sterols (such as ergosterol), chitosan, triterpenes, etc., which are considered to be potential agents for some previously healthy properties. The intake of mushrooms has a cholesterol-lowering or hypocholesterolemic effect which has been elucidated by different mechanisms, such as lowering of very-low-density lipoproteins (VLDL), improving lipid metabolism, inhibiting the activity of HMG-CoA reductase and therefore, prevents the development of atherosclerosis (Figure 3). Antioxidants and anti-inflammatory compounds found in mushrooms also reduce the risk of atherosclerosis [26]. Ganoderma lucidum play a curicral role in mitigating the toxicity of Adriamycin, where, Adriamycin treatment raised the number of marker enzymes found in serum including aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH). In order to increase lipid peroxidation (LPO), adriamycin significantly decreased antioxidant enzymes in the cardiac tissues, including glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Adriamycin has also been shown to considerably lower glutathione (GSH) levels. This study has shown that G. Lucidum extracts have significant antioxidant properties and protect the heart from the free radical-mediated toxicity of adriamycin. G. Lucidum extract retrieves free radicals and also increases the levels of glutathione and antioxidant enzymes [33]. Important findings show that the edible mushrooms could be used as possible sources of novel hypocholesterolemia agents. Few studies have identified the levels of sterols, b-glucans, and HMGCoA-red as inhibitors in mushrooms. Ergosterol was the most plentiful sterol recorded in all the samples examined, apart from G. lucidum, which had identical levels of ergosterol and ergosta-7,22-dienol. P. ostreatus, G. lucidum, A. aegerita, and L. edodes mushrooms had high levels of b-glucan content, whereas A. Blazeii, A. Bisporus, and L. procera had low levels of β-glucan content. Because of the presence of lovastatin, a statin found in mycelia broths and its fruiting bodies, the oyster mushroom (Pleurotus spp.) reduces blood cholesterol levels. As a result, a mixture of bioactive supplements improves the nutritional ability of different mushrooms to lower serum cholesterol levels [31]. A study has assessed the effect of different mushroom-like Lentinus edodes, Auricularia polytricha, and Flammulina velutipes preparations on the levels of cholesterol in the rats which showed that the preparation of dried mushrooms significantly reduced plasma cholesterol levels. Lentinus edodes was more effective, while Auricularia polytricha (Jews-ear) and Flammulina velutipes were less effective than L. edodes, Kohshin. However, ergosterol supplements have caused a marked decrease in hepatic cholesterol levels [34]. A previous study, focusing on the hypolipidemic effects of polysaccharides, isolated from Pholiota Nameko (PNPS-1) was conducted on hyperlipidemic Wistar rats. The rats were treated with PNPS-1 at different doses which reduced very-low-density: lipoprotein/low-density lipoprotein cholesterol, triacylglycerol, phospholipids, and increased the atherogenic index and high-density lipoprotein cholesterol in the serum. PNPS-1 also improved pathological changes in the coronary arteries of hyperlipidemic rats. These results suggest that PNPS-1 significantly reduces the development of hyperlipidemia and could be used as a potential therapeutic agent for CVD [35]. Anti-atherogenic and antiatherosclerotic effects of different mushrooms belonging to the genera: Armillaria, Agaricus, Boletus, Collybia, Cortinfrius, Coriolus, Flammulina, Hirneola, Lentinus, Ganoderrna, Lyophyllurn, Sarcodon, Pleurotus, Tricholoma, and Trenella were detected in human intima aortic culture. The results showed that anti-atherosclerotic, anti-atherogenic, and hypolipidemic effects of certain species of mushrooms allow us to speculate that these edible fungi are beneficial dietary supplements that might be utilized in prophylactics and to a limited extent, in atherosclerotic medicines. Furthermore, the extraction and purification of the active substance from these mushrooms may result in the development of a strong anti-atherosclerotic medicine [36]. Among the Pleurotus species, P. ostreatus was the best candidate for the prevention and treatment of atherosclerosis because it has been shown to contain a large number of antiatherosclerotic agents such as ergothionein, lovastatin, and chrysin [37].

Figure 3.

Mushroom active compounds against cardiovascular diseases (CVDs).

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3. Antidiabetic activity of mushroom biomolecules

Mushrooms are fungi that either grow above or below the ground. These are the macro fungi that can be easily seen with the naked eye. Mushrooms have been used since ancient times by the people of India and China or their medicinal properties. Nowadays many countries are consuming mushrooms for not only their unique flavor but also for their culinary effects. As many studies have revealed that mushrooms are rich sources of: proteins, carbohydrates, vitamins (B1, B2, B12, C, D, and E) and minerals like Mn, Mg, Se, Ca, Na, Cu, K, and Fe [38]. These nutritional factors in mushrooms have made it very efficient to fight diabetes. In vitro and in vivo studies have shown that the extract of mushrooms can reduce the expression of proinflammatory cytokines, induced by lipopolysaccharides which further improved the glucose uptake in skeletal muscle cell lines [39].

One of the most active biomolecules of mushrooms is β-glucans, a polysaccharide that can protect the pancreatic tissue from damage and restore the function of b-cells which helps to lower the blood glucose levels [40]. The low energy, lack of cholesterol and fats, less carbohydrates, and high minerals, proteins and vitamins made mushrooms an ideal food for diabetic patients. The consumption of mushrooms for a few days only can help to manage the low-density lipoproteins, total cholesterol, high-density lipoprotein, triglycerides levels in serum [10]. Besides bioactive molecules, mushrooms are very good in antioxidants activity and are also a good source of dietary fibers and water. Some of the most culinary properties containing mushrooms are Agaricus bisporus, Agaricus subrufescens, Cordyceps millitaris, Cordyceps sinensis, Grifola frondosa, Ganoderma lucidum, Phellinus linteus, Pleurotus flabellatus, Pleurotus citrinopileatus, Pleurotus ostreatus, Poria cocos [10, 41]. Extracts of Ganoderma lucidum contain: polysaccharides, triterpenoids, proteoglycans, and proteins which have been shown to reduce blood glucose levels. The proteoglycans of G. lucidum inhibit the tyrosine phosphatase 1B protein in diabetic patients. G. lucidum has proven to be very effective in controlling diabetes. Moreover, the triterpenoid from G. lucidum inhibits the aldose reductase and a-glucosidase enzymes which are responsible for the elevation of postprandial glucose levels [42]. Polysaccharides from G. atrum (PSG-1) increase insulin sensitivity and lower the serum lipid by increasing and decreasing the expression levels of Bcl-2 and Bax, respectively in pancreatic cells [43].

Heteropolysaccharides are one of the bioactive molecules of Pleurotus ostreatus that control diabetes by activating the Glycogen synthase kinase 3 (GSK3) by phosphorylation and facilitating the translocation of glucose transporter type 4 (GLUT4) in streptozotocininduced diabetic rats [44]. Lentinula edodes promote the growth of gut microbiota, which play a very important role to balance the energy in diabetic patients. Another mushroom, Hirsutellas inensis shows antidiabetic, antiobesogenic effects in high-fat-diet feed-mice by modification of the components of gut microbiota. The polysaccharides and fibers of mushrooms act as prebiotics that helps in the treatment of diabetic patients [45]. Recently, researchers have found the potential effects of mushrooms in diabetic nephropathy conditions. Polysaccharides from Auricularia auricula are very helpful in promoting the oxidation of glucose. This polysaccharide protects against diabetic nephropathy by the regulation of creatinine, inflammatory factors, blood urea nitrogen, and urine protein. Polysaccharides isolated from Flammulina velutipes provided protection against reactive oxygen species (ROS) and reduced the level of malondialdehyde (MDA) in the kidney. The studies have also revealed that the proteoglycans from Ganoderma lucidum can restore kidney function by providing antioxidant activity [46]. According to a study conducted by Chou, Kan, Chang, Peng, Wang, Yu, Cheng, Jhang, Liu and Chuu [47], low molecular weight polysaccharide of Inonotus obiquus (LIOP) significantly reduces the expression of NF-jB and Transforming growth factor-beta (TGF-b) in a dose-dependent manner [48]. They find that LIOP treatment can improve glucolipotoxicity induced renal fibrosis in diabetic nephropathy mice. Hypsizigusm armoreus have been used to examine its protective effect on the liver, kidney, and pancreas. The spent mushroom compost polysaccharide (SCP), its enzymatic lysates (ESCP), and acid-based hydrolyzed SCP (ASCP) were tested in streptozotocin-induced mice and found that it increased the: catalase, superoxide dismutase, and glutathione peroxidase activity whereas, it reduced the lipid peroxide and malonaldehyde levels [49]. a-glucosidase inhibiting polysaccharide (ePS-F4-1) with triterpenoids had been purified from Coriolus versicolor. Another bioactive molecule, MT-a-glucan (polysaccharide) from Grifola frondosa increases the expression of Interleukin-2 (IL-2) and prevents the injury of b-cells [50]. Submerged cultured mycelium of Agaricus brasiliensis and G. lucidum has shown a protective effect on red blood cells (RBCs) in Streptozotocin (STZ)-induced diabetic rats [51].

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4. Anticancer activity

Reproductive system diseases are responsible for several types of cancers like: prostate cancer, breast cancer, ovarian cancer, cervical cancer, uterine cancer, colorectal cancer etc. The bioactive compounds present in the mushroom are playing an important role in the treatment of reproductive disease-associated cancers. There are several medicinal mushrooms like Ganoderma lucidum, Trametes versicolor, Inonotus obliquus, Fomitopsis officinalis, etc. which are frequently used in the treatment of cancer. Prostate cancer is the third leading cause of cancer deaths in men worldwide and the utmost common male malignancy in several western countries. The incidence rate of prostate cancer is highest in the United States, lower in European countries and lowest in Asia [52]. The common risk factor related to prostate cancer is age, obesity, family history, environmental factors and dietary factors [53]. Retinoblastoma (Rb) and p53 (tumor suppressor gene) play a vital role in the progression of prostate cancer [54]. The anomalous expression in growth factors and receptors such as: transforming growth factor-a (TGF-a), epidermal growth factor (EGF), transforming growth factor-b (TGF-b), HER-2/neu, and c-erbB-3 oncogenes [41] also lead to the malignant prostate cancer. To combat these problems, natural compounds and fungal metabolites can be used as inhibitors for targeting cancerous cells in certain cancers [55, 56, 57, 58]. Ganoderma lucidum belongs to the Ganoderma genus, oriental medicinally mushroom, which have been widely used in Asian countries for centuries to cure different diseases including cancer. Plenty of species of this genus have antiviral, antibacterial, antifungal, anticancer, and immune-stimulating activities [59]. These activities were due to the production of various bioactive compounds present in medicinally mushrooms such as proteins [60, 61, 62], terpenes, sterols, and polyphenols, etc. The dried powder of G. lucidum is used as dietary supplements and is also used as a chemotherapeutic agent for cancer therapy. It induced the apoptosis of prostate cancer (PC-3) cells by lowering the expression of NF-jB-mediated Bcl-2 and Bcl-xl expression while the upregulation of the Bax protein [63]. The extracts of G. lucidum suppress the proliferation of cells and induce the G1 cell cycle in prostate cancer and breast cancer cells line [64]. Trametes versicolor, is a medicinal mushroom, belongs to the class Agaricomycetes shows anti-proliferative effects upon hepatocellular carcinoma cells (HCC), prostate cancer (DU145) and human breast cancer (4 T1) [42]. Several studies suggested that in T. versicolor β-glucan-based polysaccharopeptide fraction (PSP) and polysaccharide fraction (PSK) are present which are used as immunotherapeutic anticancer agents [65]. PSP activates cells of the immune system by enhancing the secretion of histamine, chemokines and cytokines such as interleukins (IL-1b and IL-6), TNF-a and prostaglandin E which excites dendrite and T-cell infiltration into tumor and lowers the damaging undesirable effects of chemotherapy [66]. Breast cancer is becoming one of the most common leading causes of mortality among women. The molecular subtypes of breast cancer are identified by gene expression profiles and lead to the identification of biomarkers that may ease the prognosis and treatment of cancer [67]. The molecular and pathological marker for the treatment of breast cancer is based on the presence or absence of progesterone receptors (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) [67]. To overcome this problem, the medicinally mushroom is widely utilized in modern integrative oncology and given to patients regularly. The clinical results suggested that T. versicolor inhibits the human triple-negative breast cancer cells (MDA-MB-231) in the in vitro culture and reduced their growth [68] and is used as a supplement in the treatment of breast cancer. The mushroom Inonotus obliquus, often known as Chaga mushroom, belongs to the Agaricomycetes class and is widely used as traditional medicine for cancer therapy in Korea, China, Japan, and Russia [69]. Scientists illustrated that the water extracts of Chaga mushroom have shown cytotoxic and antimitotic activity on HeLa cells. The polysaccharides from I. obliquus inhibit the migration of cancer cell lines and shows anti-metastatic activities in vitro. The polysaccharide suppressed the NF-jB, PI3K/AKT and MAPKs signaling pathways by blocking activity and the expression of matrix metalloproteinases 2 and 9 (MMP) [70]. The studies confirmed that the Chaga mushroom has Wnt/β- catenin-inhibitory properties due to the presence of one major compound namely inotodiol which suppressed the breast cancer proliferation via the Wnt-dependent signaling pathway in a diabetic rat model [71].

The bioactive compounds present in the Ganoderma species are a viable alternative to fight breast cancer. The aqueous extracts of G. lucidum, G. sinense and G. tsugae were widely used against breast cancer cells. The data illustrated that the aqueous extract of these species has anti-proliferative activities against MCF-7 cells and MDA-MB-231 cells. However, the aqueous extract of G. tsugae was most effective against MCF-7 cells, although the activity of other Ganoderma species is similar to MDA-MB-231 cells. It also established that the extract did not show any cytotoxic activity against human noncancerous epithelial cells [72]. Several results showed that G. lucidum suppressed the proliferation of MDA-MB-231 cells in a dose and time-dependent manner [64]. The spore powder of G. lucidum also exhibited potent cytotoxic effects in the MDA-MB-468, triple-negative breast cancer cell lines, and SUM-102cell line and overexpressing the HER2 gene in MDA-MB435 [73]. Fomitopsis officinalis belongs to the family Polyporaceae and is generally known as ‘Agarikon.’ The fruiting bodies of mushrooms are used as a medicine in Western Europe, North America, and Asian countries for the treatment of gastric cancer, asthma, cough, and pneumonia [74]. Some auspicious evidence illustrated that using fungal extracts can help prevent breast and gastrointestinal cancers. Some studies confirmed antiviral, antibacterial, anticancer, and anti-inflammatory activity of crude extract of F. officinalis in different forms of cancers [75]. In F. officinalis extract, Lanostane-type triterpenoids, was reported which showed promising anticancer activity. Scientists showed that the ethanol extracts of F. officinalis are more effective in comparison with water extract against human breast cancer (MDAMB-231) cells, colon cancer (HCT-116), lung cancer (A549), mouse sarcoma 180 (S-180) and hepatoma (HepG2) cells [75].

Figure 4 shows the therapeutic activity of mushrooms and their biomolecules in the treatment of different forms of cancer. The immune system plays a very contributing role in the progression of tumors toward cancer. Mushroom shows its therapeutic activity by targeting the components of the immune system and also modulates the apoptotic processes. Figure 4 suggests the therapeutic activity of mushrooms by modulating the different components of the immune system and also regulates the apoptotic processes in cancerous cells [76, 77, 78].

Figure 4.

Antitumor mechanism of bioactive compounds in medicinal mushroom.

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5. Biomolecules of mushrooms in neurodegenerative diseases (NDs)

Bioactive molecules in mushrooms also prevent the progression of different NDs. Motor symptoms linked with Parkinson’s disease (PD) are significantly prevented by a diet rich in mushroom supplements. In addition, the clinical symptoms of PD were also alleviated by mushroom supplements rich in phytochemicals, minerals, and vitamins [79]. Anti-inflammatory and antioxidative activity is exhibited by dietary mushrooms containing significant quantities of carotenoids, polysaccharides, minerals, polyphenols, and vitamins [80]. The two major factors that are responsible for the progression of PD are oxidative stress and neuroinflammation. Thus, the biomolecules present in edible mushrooms offer significant neuroprotection by their anti-oxidative and anti-inflammatory activity by preventing the progressive degeneration of dopaminergic neurons [79]. One of the major factors responsible for the generation of neuroinflammation in PD is the activation of microglial cells. Ganoderma lucidum extract (GLE) inhibited the activation of these microglial cells and ultimately preventing the progressive degeneration of dopaminergic neurons in PD. Tumor necrosis factoralpha (TNF-a) and interleukin-1b (IL-1b) are the examples of some important proinflammatory cytokines whose expression was downregulated by GLE in a dose-dependent manner and can be treated by natural antibiotics reported in [81]. Further progression of PD is prevented by inhibition of these proinflammatory cytokines by GLE. Thus, the treatment of PD, GLE should be utilized as an effective anti-inflammatory medication [82]. For the treatment of PD, niacin-rich food can be very beneficial and offers significant protective activity. Niacin-rich mushroom content offers potential therapeutic efficacy in the treatment of PD [83]. In the rotenone intoxicated model of PD, neuroprotective activity was shown by the Agaricus blazei extract (ABE). ABE also improves rotenone-induced non-motor and motor complications in PD. Therefore, for the treatment of PD, ABE might also be utilized as a nutritional supplement [84]. Some herbal plants like Tinospora cordifolia, Withania somnifera, Mucuna pruriens (Mp), and the essential oils also exhibit neuroprotective activity similar to mushrooms in toxin-induced PD mouse models [85, 86, 87]. In addition, bioactive components of Mp like Ursolic acid also exhibits potent antioxidative and anti-inflammatory property in toxin-induced PD model [88, 89, 90]. Chlorogenic acid also exhibits a similar AntiParkinsonian activity in the mouse model of PD [91]. Similar to PD, in Alzheimer’s disease (AD), nutritional mushroom provides important biomolecules that help to improve the quality of AD patients. Neuroinflammation along with oxidative stress mainly contributes to the pathogenesis of AD. The redox status in the cell of AD is significantly impaired [1]. Mushrooms have all the essential components that restore the normal balance of the redox system in AD models and patients. Proper and accurate functioning of mitochondria is required to maintain energy homeostasis. The synthesis of vital energy equivalents is hampered by abnormal mitochondrial functioning. In the neuroprotective network, inflammasome is an example of a very vital component. In AD, mitochondrial functioning was improved by Coriolus and Hericium. Normal redox balance was also maintained by these two nutritional mushrooms. Thus, energy homeostasis in AD was maintained by the above-mentioned two mushrooms by their antioxidative and anti-inflammatory properties [92]. One of the best examples of both medicinal and edible mushrooms is the Hericium erinaceus (HE). Both in vitro and in vivo model systems show the neuroprotective activity of HE. The aqueous extract of HE rich in a mycelium polysaccharide shows potent anti-apoptotic activity in l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cell lines. The AD mouse model induces by the combination of AlCl3 with D-galactose. The aqueous extract of HE prevents the further progression of AD by its neuroprotective potential. Behavioral abnormalities were also improved by the aqueous extract of HE in the AD mouse model. In a dosedependent manner, HE is responsible for the enhancement of choline acetyltransferase (ChAT) and acetylcholine (Ach) in serum and hypothalamus. To avert the pathogenesis of AD, the hypothalamus and serum level of Ach and ChAT is very vital. HE could be an efficient neuroprotective agent in AD and for some other neurodegenerative diseases [22]. For the treatment of different diseases, Coriolus versicolor (CV) mushroom is also widely utilized as a nutritional supplement. The oxidative stress and neuroinflammation were considerably reduced by the CV in AD. CV also improve the quality of mitochondria and restores the normal redox balance [92]. Human wellness was effectively maintained by the bioactive molecules present in prebiotics such as legumes [93, 94, 95], spirulina [96], biological nanoparticles [93, 97], mushroom [30]. Similar to PD, some herbal plants like Bacopa monnieri, Withania somnifera, Eclipta alba, Moringa oleifera and cucumber also improves cognitive function as suggested by some researchers [98, 99, 100, 101, 102, 103]. In addition, the neuroinflammatory pathways are also significantly modulated by a variety of medicinal mushrooms in AD [104]. In Huntington’s disease (HD), the therapeutic efficacy was also shown by medicinal, non-edible, and edible mushrooms and their bioactive components. Cognitive dysfunction is the very basic clinical feature of HD. In the edible mushroom Polyozellus multiplex, Polyozellin is a very important biomolecule having significant therapeutic activity. In the HD model, glutamate-induced mouse hippocampal neuronal HT22 cell death was significantly ameliorated by Polyozellin by apoptosis and the MAPK pathway. In HT22 cells, biochemical anomalies like lipid peroxidation and reactive oxygen species (ROS) were reduced by Polyozellin. Therefore, Polyozellin might be utilized for the treatment of HD patients in near future [105]. In the animal model of multiple sclerosis (MS), the disease conditions were ameliorated by Piwep, a mushroom extract from Phellinus igniarius. The dietary mushrooms and their bioactive components also improve the disease pathology in MS as with other NDs [106]. NFjB and Nrf2 mediated neuroinflammatory pathways are mainly responsible for mitochondrial dysfunction and ultimately cause progressive neurodegeneration in all NDs. Thus, the biomolecules of mushrooms play a very potential role to reduce the pathogenesis associated with NDs. Further studies will need to characterize more biomolecules in mushrooms and test their efficacy in several NDs.

References

  1. 1. Valverde ME, Hernández-Pérez T, Paredes-López O. Edible mushrooms: Improving human health and promoting quality life. International Journal of Microbiology. 2015:1-14. DOI: 10.1155/2015/376387
  2. 2. Singh M. Mushroom Biotechnology: The rise of the fallen. International Society for Optics and Photonics. 2019:1-5. doi: 10.1117/12.2511366
  3. 3. Benjamin DR. Mushrooms: Poisons and panaceas. A Handbook for Naturalists, Mycologists, and Physicians. 1995:242-263
  4. 4. Chang S-T. Development of the world mushroom industry and its roles in human health. Mushroom biology and biotechnology. 2007;213:1
  5. 5. Pohleven J, Obermajer N, Sabotič J, Anžlovar S, Sepčić K, Kos J, et al. Purification, characterization and cloning of a ricin B-like lectin from mushroom Clitocybe nebularis with antiproliferative activity against human leukemic T cells. Biochimica et Biophysica Acta (BBA)-General Subjects. 2009;1790(3):173-181
  6. 6. Heo J-C, Nam S-H, Nam D-Y, Kim J-G, Lee K-G, Yeo J-H, et al. Anti-asthmatic activities in mycelial extract and culture filtrate of Cordyceps sphecocephala J201. International Journal of Molecular Medicine. 2010;26(3):351-356
  7. 7. Cheung P. The nutritional and health benefits of mushrooms. Nutrition Bulletin. 2010;35(4):292-299
  8. 8. Gunawardena D, Bennett L, Shanmugam K, King K, Williams R, Zabaras D, et al. Anti-inflammatory effects of five commercially available mushroom species determined in lipopolysaccharide and interferon-γ activated murine macrophages. Food Chemistry. 2014;148:92-96
  9. 9. Kalač P. A review of chemical composition and nutritional value of wild-growing and cultivated mushrooms. Journal of the Science of Food and Agriculture. 2013;93(2):209-218
  10. 10. Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, et al. White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutrition Research. 2010;30(1):49-56
  11. 11. Kim HM, Kang JS, Kim JY, Park S-K, Kim HS, Lee YJ, et al. Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse. International Immunopharmacology. 2010;10(1):72-78
  12. 12. Miyamoto I, Liu J, Shimizu K, Sato M, Kukita A, Kukita T, et al. Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum. European Journal of Pharmacology. 2009;602(1):1-7
  13. 13. Deepalakshmi K, Sankaran M. Pleurotus ostreatus: An oyster mushroom with nutritional and medicinal properties. Journal of Biochemical Technology. 2014;5(2):718-726
  14. 14. Geng X, Tian G, Zhang W, Zhao Y, Zhao L, Wang H, et al. A Tricholoma matsutake peptide with angiotensin converting enzyme inhibitory and antioxidative activities and antihypertensive effects in spontaneously hypertensive rats. Scientific Reports. 2016;6(1):1-9
  15. 15. Kobori M, Yoshida M, Ohnishi-Kameyama M, Takei T, Shinmoto H. 5α, 8α-Epidioxy-22E-ergosta-6, 9 (11), 22-trien-3β-ol from an edible mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells. Biological and Pharmaceutical Bulletin. 2006;29(4):755-759
  16. 16. Ren G, Zhao Y-p, Yang L, Fu C-X. Anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis. Cancer Letters. 2008;262(2):190-200
  17. 17. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clinical Interventions in Aging. 2018;13:757
  18. 18. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links. International Journal of Physiology, Pathophysiology and Pharmacology. 2019;11(3):45
  19. 19. Dasgupta A, Acharya K. Mushrooms: An emerging resource for therapeutic terpenoids. 3. Biotech. 2019;9(10):1-14
  20. 20. Lee K-H, Morris-Natschke SL, Yang X, Huang R, Zhou T, Wu S-F, et al. Recent progress of research on medicinal mushrooms, foods, and other herbal products used in traditional Chinese medicine. Journal of Traditional and Complementary Medicine. 2012;2(2):1-12
  21. 21. Ganeshpurkar A, Rai G, Jain AP. Medicinal mushrooms: Towards a new horizon. Pharmacognosy Reviews. 2010;4(8):127
  22. 22. Zhang Y, Hu T, Zhou H, Zhang Y, Jin G, Yang Y. Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats. International Journal of Biological Macromolecules. 2016;83:126-132
  23. 23. Chaturvedi VK, Agarwal S, Gupta KK, Ramteke PW, Singh M. Medicinal mushroom: Boon for therapeutic applications. 3 Biotech. 2018;8(8):1-20
  24. 24. Dubey S, Yadav C, Bajpeyee A, Singh MP. Effect of Pleurotus fossulatus aqueous extract on biochemical properties of liver and kidney in streptozotocin-induced diabetic rat. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020;13:3035
  25. 25. Cao S-Y, Zhao C-N, Gan R-Y, Xu X-Y, Wei X-L, Corke H, et al. Effects and mechanisms of tea and its bioactive compounds for the prevention and treatment of cardiovascular diseases: An updated review. Antioxidants. 2019;8(6):166
  26. 26. Guillamón E, García-Lafuente A, Lozano M, Rostagno MA, Villares A, Martínez JA. Edible mushrooms: Role in the prevention of cardiovascular diseases. Fitoterapia. 2010;81(7):715-723
  27. 27. Elkhateeb WA, Daba GM, Sheir D, El-Dein AN, Fayad W, Elmahdy EM, et al. GC-MS analysis and in-vitro hypocholesterolemic, anti-rotavirus, anti-human colon carcinoma activities of the crude extract of a Japanese Ganoderma spp. Egyptian Pharmaceutical Journal. 2019;18(2):102-110
  28. 28. Tan BL, Norhaizan ME, Liew W-P-P, Sulaiman Rahman H. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Frontiers in Pharmacology. 2018;9:1162
  29. 29. Hunt PA, Sathyanarayana S, Fowler PA, Trasande L. Female reproductive disorders, diseases, and costs of exposure to endocrine disrupting chemicals in the European Union. The Journal of Clinical Endocrinology & Metabolism. 2016;101(4):1562-1570
  30. 30. Phan C-W, Tan EY-Y, Sabaratnam V. Bioactive molecules in edible and medicinal mushrooms for human wellness. In: Mérillon J-M, Ramawat KG, editors. Bioactive Molecules in Food. Springer International Publishing AG; 2018. pp. 1-24. DOI: 10.1007/978-3-319-54528-8_83-1
  31. 31. Gil-Ramirez A, Clavijo C, Palanisamy M, Soler-Rivas C, Ruiz-Rodriguez A, Marín FR, Reglero G, et al. Edible mushrooms as potential sources of new hypocholesterolemic compounds. Villenave d’Ornon Cedex, France: Institut National de la Recherche Agronomique (INRA); 2011
  32. 32. Phan C-W, David P, Sabaratnam V. Edible and medicinal mushrooms: Emerging brain food for the mitigation of neurodegenerative diseases. Journal of Medicinal Food. 2017;20(1):1-10
  33. 33. Rajasekaran M, Kalaimagal C. Cardioprotective effect of a medicinal mushroom, Ganoderma lucidum against adriamycin induced toxicity. International Journal of Pharmacology. 2012;8(4):252-258
  34. 34. Kaneda T, Tokuda S. Effect of various mushroom preparations on cholesterol levels in rats. The Journal of Nutrition. 1966;90(4):371-376
  35. 35. Li H, Zhang M, Ma G. Hypolipidemic effect of the polysaccharide from Pholiota nameko. Nutrition. 2010;26(5):556-562
  36. 36. Ryong LH, Tertov VV, Vasil’ev AV, Tutel’yan VA, Orekhov AN. Antiatherogenic and antiatherosclerotic effects of mushroom extracts revealed in human aortic intima cell culture. Drug Development Research. 1989;17(2):109-117
  37. 37. Abidin MHZ, Abdullah N, Abidin NZ. Therapeutic properties of Pleurotus species (oyster mushrooms) for atherosclerosis: A review. International Journal of Food Properties. 2017;20(6):1251-1261
  38. 38. Lee DH, Yang M, Giovannucci EL, Sun Q , Chavarro JE. Mushroom consumption, biomarkers, and risk of cardiovascular disease and type 2 diabetes: A prospective cohort study of US women and men. The American Journal of Clinical Nutrition. 2019;110(3):666-674
  39. 39. Yang H, Hwang I, Kim S, Hong EJ, Jeung EB. Lentinus edodes promotes fat removal in hypercholesterolemic mice. Experimental and Therapeutic Medicine. 2013;6(6):1409-1413
  40. 40. Xiao C, Wu Q , Tan J, Cai W, Yang X, Zhang J. Inhibitory effects on-glucosidase and hypoglycemic effects of the crude polysaccharides isolated from 11 edible fungi. Journal of Medicinal Plants Research. 2011;5(32):6963-6967
  41. 41. Lu X, Chen H, Dong P, Fu L, Zhang X. Phytochemical characteristics and hypoglycaemic activity of fraction from mushroom Inonotus obliquus. Journal of the Science of Food and Agriculture. 2010;90(2):276-280
  42. 42. Ma H-T, Hsieh J-F, Chen S-T. Anti-diabetic effects of Ganoderma lucidum. Phytochemistry. 2015;114:109-113
  43. 43. Zhu K, Nie S, Li C, Lin S, Xing M, Li W, et al. A newly identified polysaccharide from Ganoderma atrum attenuates hyperglycemia and hyperlipidemia. International Journal of Biological Macromolecules. 2013;57:142-150
  44. 44. Ma G, Yang W, Zhao L, Pei F, Fang D, Hu Q. A critical review on the health promoting effects of mushrooms nutraceuticals. Food Science and Human Wellness. 2018;7(2):125-133
  45. 45. Martel J, Ojcius DM, Chang C-J, Lin C-S, Lu C-C, Ko Y-F, et al. Anti-obesogenic and antidiabetic effects of plants and mushrooms. Nature Reviews Endocrinology. 2017;13(3):149-160
  46. 46. Jiang X, Meng W, Li L, Meng Z, Wang D. Adjuvant therapy with mushroom polysaccharides for diabetic complications. Frontiers in Pharmacology. 2020;11:168
  47. 47. Chou Y-J, Kan W-C, Chang C-M, Peng Y-J, Wang H-Y, Yu W-C, et al. Renal protective effects of low molecular weight of Inonotus obliquus polysaccharide (LIOP) on HFD/STZ-induced nephropathy in mice. International Journal of Molecular Sciences. 2016;17(9):1535
  48. 48. Sitohy MZ, Ramadan MF. Granular properties of different starch phosphate monoesters. Starch-Stärke. 2001;53(1):27-34
  49. 49. Liu M, Song X, Zhang J, Zhang C, Gao Z, Li S, et al. Protective effects on liver, kidney and pancreas of enzymatic-and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus). Scientific Reports. 2017;7(1):1-12
  50. 50. Inoue A, Kodama N, Nanba H. Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion. Biological and Pharmaceutical Bulletin. 2002;25(4):536-540
  51. 51. Vitak T, Yurkiv B, Wasser S, Nevo E, Sybirna N. Effect of medicinal mushrooms on blood cells under conditions of diabetes mellitus. World Journal of Diabetes. 2017;8(5):187
  52. 52. Rawla P. Epidemiology of prostate cancer. World Journal of Oncology. 2019;10(2):63
  53. 53. Baillargeon J, Platz EA, Rose DP, Pollock BH, Ankerst DP, Haffner S, et al. Obesity, adipokines, and prostate cancer in a prospective population-based study. Cancer Epidemiology and Prevention Biomarkers. 2006;15(7):1331-1335
  54. 54. Hickman ES, Moroni MC, Helin K. The role of p53 and pRB in apoptosis and cancer. Current Opinion in Genetics & Development. 2002;12(1):60-66
  55. 55. Ali H, AbdelMageed M, Olsson L, Israelsson A, Lindmark G, Hammarström M-L, et al. Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer. Tumor Biology. 2019;41(6):1010428319858885
  56. 56. El-Sayed AS, Fathalla M, Yassin MA, Zein N, Morsy S, Sitohy M, et al. Conjugation of aspergillus flavipes taxol with porphyrin increases the anticancer activity of taxol and ameliorates its cytotoxic effects. Molecules. 2020;25(2):263
  57. 57. Ohlsson L, Hammarström M-L, Lindmark G, Hammarström S, Sitohy B. Ectopic expression of the chemokine CXCL17 in colon cancer cells. British Journal of Cancer. 2016;114(6):697-703
  58. 58. El-Sayed AS, Safan S, Mohamed NZ, Shaban L, Ali GS, Sitohy MZ. Induction of Taxol biosynthesis by aspergillus terreus, endophyte of Podocarpus gracilior Pilger, upon intimate interaction with the plant endogenous microbes. Process Biochemistry. 2018;71:31-40
  59. 59. Abdelbacki AM, Taha SH, Sitohy MZ, Abou Dawood AI, Hamid MM, Rezk AA. Inhibition of tomato yellow leaf curl virus (TYLCV) using whey proteins. Virology Journal. 2010;7(1):1-6
  60. 60. Osman A, El-Didamony G, Sitohy M, Khalifa M, Enan G. Soybean glycinin basic subunit inhibits methicillin resistant-vancomycin intermediate Staphylococcus aureus (MRSA-VISA) in vitro. International Journal of Applied Research in Natural Products. 2016;9(2):17-26
  61. 61. Sitohy M, CHOBERT JM, Haertlé T. Study of factors influencing protein esterification using β-lactoglobulin as a model. Journal of Food Biochemistry. 2000;24(5):381-398
  62. 62. Sitohy M, Mahgoub S, Osman A. Controlling psychrotrophic bacteria in raw buffalo milk preserved at 4 C with esterified legume proteins. LWT-Food Science and Technology. 2011;44(8):1697-1702
  63. 63. Jiang J, Slivova V, Harvey K, Valachovicova T, Sliva D. Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-κB signaling. Nutrition and Cancer. 2004;49(2):209-216
  64. 64. Lu Q-Y, Jin Y-S, Zhang Q , Zhang Z, Heber D, Go VLW, et al. Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro. Cancer Letters. 2004;216(1):9-20
  65. 65. Cui J, Chisti Y. Polysaccharopeptides of Coriolus versicolor: Physiological activity, uses, and production. Biotechnology Advances. 2003;21(2):109-122
  66. 66. Chang Y, Zhang M, Jiang Y, Liu Y, Luo H, Hao C, et al. Preclinical and clinical studies of Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Discovery Medicine. 2017;23(127):207-219
  67. 67. Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: Classification, prognostication, and prediction. The Lancet. 2011;378(9805):1812-1823
  68. 68. Jiang J, Thyagarajan-Sahu A, Loganathan J, Eliaz I, Terry C, Sandusky GE, et al. BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. Oncology Reports. 2012;28(4):1139-1145
  69. 69. Handa N, Yamada T, Tanaka R. An unusual lanostane-type triterpenoid, spiroinonotsuoxodiol, and other triterpenoids from Inonotus obliquus. Phytochemistry. 2010;71(14-15):1774-1779
  70. 70. Lee KR, Lee JS, Kim YR, Song IG, Hong EK. Polysaccharide from Inonotus obliquus inhibits migration and invasion in B16-F10 cells by suppressing MMP-2 and MMP-9 via downregulation of NF-κB signaling pathway. Oncology Reports. 2014;31(5):2447-2453
  71. 71. Zhang X, Bao C, Zhang J. Inotodiol suppresses proliferation of breast cancer in rat model of type 2 diabetes mellitus via downregulation of β-catenin signaling. Biomedicine & Pharmacotherapy. 2018;99:142-150
  72. 72. Yue GG, Fung K-P, Tse GM, Leung P-C, Lau CB. Comparative studies of various Ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro. Journal of Alternative & Complementary Medicine. 2006;12(8):777-789
  73. 73. Suárez-Arroyo IJ, Rios-Fuller TJ, Feliz-Mosquea YR, Lacourt-Ventura M, Leal-Alviarez DJ, Maldonado-Martinez G, et al. Ganoderma lucidum combined with the EGFR tyrosine kinase inhibitor, erlotinib synergize to reduce inflammatory breast cancer progression. Journal of Cancer. 2016;7(5):500
  74. 74. Grienke U, Zöll M, Peintner U, Rollinger JM. European medicinal polypores—A modern view on traditional uses. Journal of Ethnopharmacology. 2014;154(3):564-583
  75. 75. Wu H-T, Lu F-H, Su Y-C, Ou H-Y, Hung H-C, Wu J-S, et al. In vivo and in vitro anti-tumor effects of fungal extracts. Molecules. 2014;19(2):2546-2556
  76. 76. Sitohy B, Chang S, Sciuto TE, Masse E, Shen M, Kang PM, et al. Early actions of anti-vascular endothelial growth factor/vascular endothelial growth factor receptor drugs on Angiogenic blood vessels. The American Journal of Pathology. 2017;187(10):2337-2347
  77. 77. Sitohy B, El-Salhy M. Changes in the colonic enteric nervous system in rats with chemically induced colon dysplasia and carcinoma. Acta Oncologica. 2002;41(6):543-549
  78. 78. Sitohy B, El-Salhy M. A comparison between double and triple therapies of octreotide, galanin and serotonin on a rat colon carcinoma. Histology and Histopathology. 2003;1:103-110
  79. 79. Ciulla M, Marinelli L, Cacciatore I, Stefano AD. Role of dietary supplements in the management of Parkinson’s disease. Biomolecules. 2019;9(7):271
  80. 80. Kozarski M, Klaus A, Jakovljevic D, Todorovic N, Vunduk J, Petrović P, et al. Antioxidants of edible mushrooms. Molecules. 2015;20(10):19489-19525
  81. 81. Abd El-Hack ME, El-Saadony MT, Elbestawy AR, Nahed A, Saad AM, Salem HM, et al. Necrotic enteritis in broiler chickens: Disease characteristics and prevention using organic antibiotic alternatives—A comprehensive review. Poultry Science. 2021;101(2):101590
  82. 82. Zhang R, Xu S, Cai Y, Zhou M, Zuo X, Chan P. Ganoderma lucidum protects dopaminergic neuron degeneration through inhibition of microglial activation. Evidence-based Complementary and Alternative Medicine. 2011:1-9
  83. 83. Aaseth J, Dusek P, Roos PM. Prevention of progression in Parkinson’s disease. Biometals. 2018;31(5):737-747
  84. 84. Venkateshgobi V, Rajasankar S, Johnson WMS, Prabu K, Ramkumar M. Neuroprotective effect of agaricus blazei extract against rotenone-induced motor and nonmotor symptoms in experimental model of parkinson’s disease. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2018;8(2):59
  85. 85. Birla H, Rai SN, Singh SS, Zahra W, Rawat A, Tiwari N, et al. Tinospora cordifolia suppresses neuroinflammation in parkinsonian mouse model. Neuromolecular Medicine. 2019;21(1):42-53
  86. 86. Rai SN, Birla H, Singh SS, Zahra W, Patil RR, Jadhav JP, et al. Mucuna pruriens protects against MPTP intoxicated neuroinflammation in Parkinson’s disease through NF-κB/pAKT signaling pathways. Frontiers in Aging Neuroscience. 2017;9:421
  87. 87. Abd El-Hack ME, El-Saadony MT, Saad AM, Salem HM, Ashry NM, Ghanima MMA, et al. Essential oils and their nanoemulsions as green alternatives to antibiotics in poultry nutrition: A comprehensive review. Poultry Science. 2021;101(2):101584
  88. 88. Rai SN, Mishra D, Singh P, Vamanu E, Singh M. Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases. Biomedicine & Pharmacotherapy. 2021;137:111377
  89. 89. Rai SN, Zahra W, Singh SS, Birla H, Keswani C, Dilnashin H, et al. Anti-inflammatory activity of ursolic acid in MPTP-induced parkinsonian mouse model. Neurotoxicity Research. 2019;36(3):452-462
  90. 90. Zahra W, Rai SN, Birla H, Singh SS, Rathore AS, Dilnashin H, et al. Neuroprotection of rotenone-induced parkinsonism by ursolic acid in PD mouse model. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2020;19(7):527-540
  91. 91. Singh SS, Rai SN, Birla H, Zahra W, Rathore AS, Dilnashin H, et al. Neuroprotective effect of chlorogenic acid on mitochondrial dysfunction-mediated apoptotic death of DA neurons in a Parkinsonian mouse model. Oxidative Medicine and Cellular Longevity; 2020:1-14
  92. 92. Trovato Salinaro A, Pennisi M, Di Paola R, Scuto M, Crupi R, Cambria MT, et al. Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: Modulation by nutritional mushrooms. Immunity & Ageing. 2018;15(1):1-8
  93. 93. Abd El-Hack ME, El-Saadony MT, Shafi ME, Alshahrani OA, Saghir SA, Al-Wajeeh AS, et al. Prebiotics can restrict Salmonella populations in poultry: A review. Animal Biotechnology; 2021:1-10. DOI: 10.1080/10495398.2021.1883637
  94. 94. Saad AM, Elmassry RA, Wahdan KM, Ramadan FM. Chickpea (Cicer arietinum) steep liquor as a leavening agent: Effect on dough rheology and sensory properties of bread. Acta Periodica Technologica. 2015;46:91-102
  95. 95. Saad AM, Sitohy MZ, Ahmed AI, Rabie NA, Amin SA, Aboelenin SM, et al. Biochemical and functional characterization of kidney bean protein alcalase-hydrolysates and their preservative action on stored chicken meat. Molecules. 2021;26(15):4690
  96. 96. Abdel-Moneim A-ME, El-Saadony MT, Shehata AM, Saad AM, Aldhumri SA, Ouda SM, et al. Antioxidant and antimicrobial activities of Spirulina platensis extracts and biogenic selenium nanoparticles against selected pathogenic bacteria and fungi. Saudi Journal of Biological Sciences. 2022;29(2):1197-1209
  97. 97. El-Saadony MT, Saad AM, Taha TF, Najjar AA, Zabermawi NM, Nader MM, et al. Selenium nanoparticles from lactobacillus paracasei HM1 capable of antagonizing animal pathogenic fungi as a new source from human breast milk. Saudi Journal of Biological Sciences. 2021;28(12):6782-6794
  98. 98. Chaudhari KS, Tiwari NR, Tiwari RR, Sharma RS. Neurocognitive effect of nootropic drug Brahmi (Bacopa monnieri) in Alzheimer’ disease. Annals of Neurosciences. 2017;24(2):111-122
  99. 99. Mahaman YAR, Huang F, Wu M, Wang Y, Wei Z, Bao J, et al. Moringa oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments. Journal of Alzheimer’s Disease. 2018;63(3):1141-1159
  100. 100. Mehla J, Gupta P, Pahuja M, Diwan D, Diksha D. Indian medicinal herbs and formulations for alzheimer’s disease, from traditional knowledge to scientific assessment. Brain Sciences. 2020;10(12):964
  101. 101. Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proceedings of the National Academy of Sciences. 2012;109(9):3510-3515
  102. 102. El-Saadony MT, Saad AM, Elakkad HA, El-Tahan AM, Alshahrani OA, Alshilawi MS, et al. Flavoring and extending the shelf life of cucumber juice with aroma compounds-rich herbal extracts at 4° C through controlling chemical and microbial fluctuations. Saudi Journal of Biological Sciences. 2022;29(1):346-354
  103. 103. Saad AM, El-Saadony MT, Mohamed AS, Ahmed AI, Sitohy MZ. Impact of cucumber pomace fortification on the nutritional, sensorial and technological quality of soft wheat flour-based noodles. International Journal of Food Science & Technology. 2021;56(7):3255-3268
  104. 104. Kushairi N, Tarmizi NAKA, Phan CW, Macreadie I, Sabaratnam V, Naidu M, et al. Modulation of neuroinflammatory pathways by medicinal mushrooms, with particular relevance to Alzheimer’s disease. Trends in Food Science & Technology. 2020;104:153-162
  105. 105. Yang E-J, Song K-S. Polyozellin, a key constituent of the edible mushroom Polyozellus multiplex, attenuates glutamate-induced mouse hippocampal neuronal HT22 cell death. Food & Function. 2015;6(12):3678-3686
  106. 106. Li L, Wu G, Choi BY, Jang BG, Kim JH, Sung GH, et al. A mushroom extract Piwep from Phellinus igniarius ameliorates experimental autoimmune encephalomyelitis by inhibiting immune cell infiltration in the spinal cord. BioMed Research International; 2014:1-14

Written By

Ahmed M. Saad, Mahmoud Z. Sitohy, Belal A. Omar, Mohamed T. El-Saadony and Basel Sitohy

Submitted: 26 February 2022 Reviewed: 02 March 2022 Published: 13 June 2022