Data inclusion and exclusion criteria

This review outlines the current knowledge from the one hundred and thirty-three patent literature centering on the pharmacological potential of mushrooms, including as a single component—extract/powder (51) and/or bioactive ingredient (32) or multiple spp. (35), or in a polyherbal formulation comprising less than or equal to five other herbs (15).

Patents pertaining to methods of mushroom cultivation and extraction, non-therapeutic usage, such as methods of isolating bioactive compounds from mushroom extracts for cosmeceuticals, food, and nutraceuticals, are not included in the scope of this review. A large set of two hundred and one patents, mostly claiming polyherbal formulations comprising six or more other herbs along with a mushroom and/or its bioactive constituent, is not included in the scope of this review. The majority of such patents either broadly disclosed mushrooms as only an optional ingredient in the pharmaceutical composition, or claimed the therapeutic activity arising particularly from an active ingredient in the composition other than mushrooms. A few patent documents disclosing endophytic fungi are not included in the scope of this review.

Anti-cancer activity

Latest reports propose the control of cancerous cell proliferation by mushrooms in the treatment of a variety of cancers [12]. Medicinal mushrooms have also been approved as an addition to standard cancer treatments in Japan and China, either alone or combined with radiation or chemotherapy. Varieties such as Ganoderma lucidum, Trametes versicolor or Coriolus versicolor, L. edodes, and Grifola frondosa are being studied for their effects on the immune system and on tumor cells. According to a recent report, it is thought that the polysaccharides (β-glucans) in mushrooms strengthen the immune system to fight cancer [13]. Twenty-four patents were identified that indicate the use of mushrooms and/or their isolated phytochemicals with anticancer activity. We found that the majority of research on anticancer is carried out using the Ganoderma variety. An Indian patent assigned to Amala Cancer Research Center Society has claimed a natural edible chemotherapeutic agent comprising concentrated defatted methanolic extract from Morchella esculenta exhibiting tumor inhibition of at least 85% per 500 mg/kg body weight treatment [14]. Pharmaceutical sediments containing ethanol extract of Auricularia polytricha are claimed to decrease the proliferation and expression of colon cancer cells and effectively inhibit the growth of tumor cells without any side effects [15]. Two USA patents have claimed the anticancer activity of bioactive compounds of G. lucidum extract (GLE) and their selective efficacy against breast cancer [16, 17]. In one patent, the inventor discloses the inclusion of GLE in the range of 100–450 mg per dose in a polyherbal composition. The β-glucan polysaccharides and triterpenoids in the extract not only promote apoptosis in cancer cells, but additionally downregulates estrogen-α receptors, cellular migration and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, provides anti-angiogenic effect through down regulation of vascular endothelial growth factor (VEGF), and inhibits metalloproteinase (MMP-9). Further, the complex synergistic combination with other constituents (quercetin, Emblica officinalis, indole-3-carbinol, catechins, Allium sativum) and minerals (iodine, selenium) enables curtailed dosage, avoiding the possible adverse effects resulting from use of several of the ingredients [16]. In the other patent, structures of the seven most abundant G. lucidum extracted compounds, and their selective efficacy against triple negative breast cancer (TNBC), inflammatory breast cancer (IBC), and other human cancer cell types, including both solid and blood malignancies, are disclosed, thereby confirming their potential as anticancer agents. While 5,6-dehydroergosterol, a bioactive compound purified from the GLE, was demonstrated as the single most biologically active compound against IBC models with promising half maximal effective concentration (EC₅₀) values in the low micromolar range (SUM-149) and ample therapeutic index in normal cells (BJ, HMEC), its sulfonamide derivatives showed improved bioavailability [17]. A Chinese patent has disclosed an injectable formulation using GLE in a traditional Chinese Shuganning preparation showing an additive effect in treating breast cancer when combined with 5-fluorouracil (5-FU) [18]. Many inventors have commonly exploited the synergistic potential of cannabinoids and mushroom-based compositions for effective cancer treatment. An international application by Cannabotech has claimed the combination of cannabinoids and multiple mushrooms used as an adjunctive therapy to a conventional therapy for treating breast cancer [19]. Another USA patent by Apollon Formularies Plc. has also claimed a composition comprising aqueous or ethanolic extract of one or more of an edible or medicinal mushroom, and at least one cannabinoid, along with additional terpenes, and flavonoids for the treatment of various cancer types [20]. Alvit Lcs Pharma Ltd. has claimed a composition comprising a synergistic combination of medicinal mushroom extracts such as G. lucidum, or Cordyceps sinensis, and Cannabis derived compound tetrahydrocannabinol (THC) for treating pancreatic cancer in mammalian subjects [21]. Another pharmaceutical composition comprising Phellinus linteus derived hispidine as an active ingredient, in combination with an anticancer agent selected from the group consisting of gemcitabine, gefintip, cisplatin, paclitaxel, oxaliplatin, and 5-FU in a ratio of 1:(0.004 to 0.02) is reported for treating pancreatic cancer. The synergistic combination can effectively treat pancreatic cancer through growth inhibition and cell death of the cancer cells [22]. Qilu University of Technology has claimed a new Inonotus hispidus strain from the wild Phellinus igniarius rich in various active ingredients such as polysaccharides, polyphenols, flavones, and triterpenes, and can be useful for preventing and treating cancer [23]. An anticancer pharmaceutical composition containing a mixture of Coprinus comatus mushroom extract, along with powder of G. lucidum, L. edodes, and Pleurotus ostreatus varieties is claimed to treat various cancers such as gastric, breast, uterine, colorectal, pancreatic, and liver cancer by suppressing the growth and spread of cancer cells, and increasing the activity of T cells with no side effects [24]. Combination therapy comprising Lactobacillus plantarum strain and herbal medicine comprising powder or extract form of Cordyceps militaris and Phellinus linteus mushrooms for anticancer activity particularly against colon cancer is claimed [25]. Pure active ingredients such as Striatal C, Striatal C’, and Striatal D isolated from Cyathus striatus (CBS 126585) extract are claimed for their use in the treatment of epithelial cell cancer by combined administration with extracts of other medicinal mushrooms selected from the group consisting of L. edodes, Coprinus, and Tremella species [26]. Medicinal formulations for cancer treatment comprising either recombinant protein from Ganoderma microsporum in a dose from 5 μg/mL to 200 μg/mL [27], or betulinic acid derivatives from Inonotus obliquus mushroom extract are claimed [28]. Two Chinese patents have claimed the anti-liver cancer potential of mushrooms. The joint application by the two assignees Ganoherb Bio Technology Fujian Co. Ltd., and Fujian Xianzhilou Biological Science & Technology Co. Ltd. disclosed a composition containing GLE and sorafenib (SF) in optimal mass concentration ratio of 112.5:4 after considering the damage caused to liver cancer HepG2 cells, and the attenuating effect on L02 cells, the CI synergy index such that GLE effectively improved the sensitivity of SF by a combined synergistic effect [29]. According to the patent application assigned to Henan University of Traditional Chinese Medicine, a novel bicyclopyrrole aldehyde compound extracted from L. edodes can act as a new auxiliary in an anti-liver cancer drug composition. The compound has an in vitro growth inhibitory activity on the liver cancer cell line (SMMC-7721), without any toxic or side effects on the normal human normal liver cell line HL-7702 [30]. Hunan Wanzhen Biotechnology Co. Ltd. has filed six patents claiming the application of the polysaccharide selenoside-II and selenoside-III extracted from P. ostreatus mushroom as anticancer active ingredient in preparation of drug composition for treating different cancer types. While the polysaccharide selenoside-II has been demonstrated to inhibit the growth of non-small lung adenocarcinoma cells [31], polysaccharide selenoside-III inhibits the growth of liver cancer cells [32], colon cancer cells [33], breast cancer cells [34], kills gastric [35] and prostate cancer cells [36]. Both polysaccharides can reduce toxic side effects while promoting the metabolism and proliferation of normal cells. In another Chinese patent an effective component of P. igniarius mycelia concentrated solution has been claimed for resisting lung cancer cell proliferation on the human lung cancer A549 cell line [37].

The distribution of mushroom varieties for various anticancer applications across the reviewed patent literature is summarized in Table 2.

Anti-infective activity

Scientists have studied the action of mushrooms as a favourable source of natural antibiotics and biofilm-preventing agents. Various species such as G. lucidum, Laetiporus sulphureus, and L. edodes, are reported to show antimicrobial activity. The methanolic extracts of Fistulina hepatica, Ramaria botrytis, and E. delica, rich in phenolics, are also reported to be effective against multi-resistant microorganisms such as Proteus mirabilis, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. While the phenolic compounds and extract of Agaricus blazei is reported for anti-quorum sensing effect, oral biofilm inhibition is known for L. edodes extract [38]. Mushroom extracts are known to demonstrate therapeutic effects against pneumonic superinfection and severe lung inflammation that often complicates COVID-19 infection. A recent review at Oslo University has stated that the antimicrobial properties of A. blazei, Hericium erinaceus, and G. frondosa mushrooms could be used to combat COVID-19 [39]. An in-depth analysis of fifteen patents under this subsection reveals that, along with mushroom extract, specific active compounds such as the P. linteus polysaccharide also contributes to the antimicrobial effect by the fungus. A USA patent assigned to Mycelium Biotech Assets Ptd. Ltd. has claimed the use of GLE in the manufacture of a medicament for the treatment of viral, bacterial, fungal, and/or protozoal infections in humans [40]. Pharmaceutical composition comprising a dry extract of G. lucidum (polysaccharide titer of 50%) is also claimed for the treatment of HPV (papilloma virus) vaginal infections [41]. Bharath Institute of Higher Education & Research in India has claimed the protection of medicinal composition comprising Ganoderma extract for antifungal and antibiofilm activity [42]. Studies have been reported for the pharmacological potential of certain mushrooms in managing skin ailments owing to their antioxidant, anti-inflammatory, and antimicrobial properties [43]. Skin care capsule formulations specifically for the treatment of acne comprising GLE in a 2:1 combination with saw palmetto are claimed by Bottled Science Ltd. in two patents. This combination reduces the concentration of dihydrotestosterone in the body and additionally, the Ganoderma sichuanense extract also boosts the immune system [44, 45]. Antiacne medicines from the extraction of L. edodes is also claimed [46]. Another antibacterial composition containing fruiting body of P. linteus mushroom ethanol extract, and more specifically, L. edodes mushrooms grown by adding fermented sulfur as an active ingredient, is claimed for broad-spectrum antibacterial activity [47]. Mushroom bioactive compounds such as daedalin A and a derivative isolated from the mycelium culture solution of Daedalea dickinsii are claimed for use in a pharmaceutical composition for disinfecting helicobacter [48]. Antiviral pharmaceutical composition with therapeutic agent originated from different edible or medicinal mushroom extracts, along with one or more cannabinoids, is reported in PCT application filed by AI Pharmaceuticals Jamaica Ltd. [49]. In another PCT application, the assignee has claimed an antiviral composition comprising a polar extract of Astraeus asiaticus, along with acyclovir in a weight ratio of 1:1 to 4:1 for use in the treatment of hand, foot and mouth disease (HFMD) [50]. Grape King Bio. Ltd. has claimed an oral composition comprising bioactive components of P. linteus mycelia for antiviral efficacy against enterovirus type 71 [51]. Anhui Senbaigu Pharmaceutical Co. Ltd. and Anhui Medical University jointly owns two patents claiming the use of P. igniarius for antiviral pharmaceutical composition. In one patent, P. igniarius extract is used alone, and in the other patent application it is claimed for use in combination with Thesium chinense compound for preparation of therapeutic drugs for treating corona virus respectively [52, 53]. While the P. igniarius extract showed significant antiviral effect by inhibiting viral replication, increasing the virus clearance rate demonstrating very low cytotoxicity on Vero cells [half-maximal inhibitory concentration (IC₅₀) of water extract was 3,408.194 μg/mL, and IC₅₀ of alcohol extract was 1,398.063 μg/mL] [52], the medicinal composition of P. igniarius and Thesium chinense compound was ideal for treating coronary pneumonia due to the combined anti-inflammatory effect of Thesium chinense and the immunity regulation effect of P. igniarius [53]. Oral pharmaceutical compositions comprising P. linteus polysaccharide extracts are also protected by Taijian Biotech for preventing the bio-membranes of the periodontal bacteria from adhering to teeth and gums [54]. A PCT application has claimed the antibacterial activity of Sarcodon aspratus extract in a composition for inhibiting oral diseases such as periodontitis, periimplantitis, dental caries, gingivitis, halitosis, etc. [55].

Anti-inflammatory activity

Mushroom bioactive metabolites, including peptides, polysaccharides, terpenes, sterols, fatty acids, phenols, and many other low molecular weight molecules, have been well reviewed for their mechanisms of action as potent anti-inflammatory agents [56]. It is well demonstrated that these compounds possess a significant inhibitory effect on the major pro-inflammatory biomarkers and associated signaling pathways both in the in vivo and in vitro settings [57]. Eight patents under this category were analyzed to evaluate the anti-inflammatory potential of mushroom materials as claimed by inventors. Therapeutic compositions comprising extracts or isolates of edible or medicinal mushroom species such as Polyporus umbellatus, and M. esculenta alone or in combination with other natural extracts are reported for enhancing the anti-inflammatory function for a variety of different inflammatory diseases including inflammatory bowel and skin disease, retinitis, gastritis, hepatitis, enteritis, arthritis, tonsillitis, laryngopharyngitis, bronchitis, pneumonia, pancreatitis and nephritis [58, 59]. The polyherbal composition comprising P. umbellatus water extract exhibited a high inhibitory effect against nitric oxide and the catalyzing enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [58]. Another patent has claimed the anti-inflammatory action of M. esculenta extract by increasing superoxide dismutase activity, and glutathione concentration [59]. In another invention, a composition comprising aqueous or ethanolic extract of one or more edible or medicinal mushrooms along with an extract from Cannabis spp. has been claimed for the treatment of inflammatory diseases [60]. A Chinese patent has provided an effective method for extracting L. edodes dregs and its use in medicament showing higher in vitro inhibition of lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 cells [61]. In another invention, a composition is claimed for treating neuroinflammation which comprises 0.01% to 99.99% of a red ginseng extract cultured from fermented complex mushroom-grain aged strain obtained by co-cultivating the fermented complex mushroom-grain ripening strain and red ginseng and extracting them with water, alcohol, or a mixed solvent [62]. Compounds in medicinal mushrooms have been reported to act in the early inflammatory phase of wound healing by promoting growth and multiplication of keratinocytes [63]. Two Korean patents have claimed a pharmaceutical composition comprising extracts of M. esculenta in combination with bentonite for wound healing [64, 65]. The compositions operate on the immune system by removing harmful bacteria and restoring the affected areas. In another Chinese application by Zhuhai Weimei Biotechnology Co. Ltd., a polysaccharide-containing biomedical dressing comprising β-glucan and chitosan from G. lucidum as the key active ingredients, along with glycerol and carbomer as auxiliary, is claimed for treating burns, and nursing of non-chronic wounds [66].

Immuno-enhancer

The amelioration and treatment of diseases associated with immune dysfunction, such as immunodeficiency and/or autoimmunity, pose significant medical and economic challenges. Mushrooms and/or their extracts have been advocated as potential immune modulators for immunotherapy and autoimmunity [79]. Mushroom constituents, including polysaccharides (β-glucans), triterpenoids, lectins, and proteins, are also reported to manifest immunomodulatory effects in the treatment of immune conditions such as multiple sclerosis (MS), rheumatoid arthritis (RA), and thyroid conditions [80]. An individual inventor has claimed a method for extracting active ingredients from mushroom species including Fomes fomentarius, G. lucidum, and dried L. edodes and further developed a formulation for enhancing immune function while minimizing side effects [81]. In another invention, a composition comprising a complex of red ginseng extract and L. edodes mycelium extract is claimed for enhancing immunity by inducing activity of B cells or T cells which are responsible for the immune system, and promoting antibody formation in splenocytes [82]. Integria Healthcare has claimed a composition comprising stacked mushroom extracts from G. lucidum, L. edodes, and/or G. frondosa for a combined synergistic effect in the treatment of conditions associated with immunological dysfunction by immunostimulation of one or more pro-inflammatory cytokines [83]. A therapeutic composition comprising the bioactive compounds styrylpyrone, thyryllorone (hypholomine B), and davarialactone derived from P. linteus (KACC93057P) is claimed for enhancing immune function by manifesting the expression of IL-6 and TNF-α of macrophages in vitro [84]. Chinese patents have also emphasized the activity of mushroom-derived polysaccharides in pharmaceutical products for enhancing immunity. In one patent the inventors have shown the improved immunoregulatory activity of three polysaccharides derived from A. bisporus namely, microbial polysaccharide (MP), and two high-purity uniform polysaccharides—polysaccharide MP-1 and MP-2 in recovering the body weight of immunocompromised mice by increasing spleen and thymus indexes, improving spleen lesion conditions, and enhancing the expression of TNF-α, NO, and IL-6 in serum of the mice [85]. Similar effect is also claimed in another Chinese patent assigned to Zhejiang Johncan Biotechnology Co. Ltd., wherein β-glucan component of average molecular weight 32,589–36,584 daltons and total polysaccharide content greater than 95% extracted from G. lucidum is shown to enhance the immunocompetence of mice by increasing the thymus and the spleen index, enhancing the NK cell killing activity, and increasing the content of IL-2 and IL-4 in serum [86].

Neurodegenerative & mental disorders

Neurodegenerative diseases (ND) are represented by progressive damage to the brain or the nervous system. Scientific research has proposed the beneficial effects of edible mushrooms in preventing age-based neuronal dysfunctions such as Parkinson’s and Alzheimer’s diseases. Mushroom species such as G. frondosa, Lignosus rhinocerotis, H. erinaceus are reported for improving cognitive functions and ND treatments [92]. Grape King Bio. has claimed a pharmaceutical composition prepared by using H. erinaceus mycelium extract, containing erinacin S as an active ingredient for improving central nervous system myelination [93]. Synergistic and entourage enhanced combinations of psilocybin from the extract of psychedelic mushroom Psilocybe cubensis, psychoactive tryptamines, and cannabinoids are also claimed for developing compositions to treat central nervous system disorders [94]. A similar composition comprising a combination of major and minor tryptamines from Psilocybe spp., such as psilocybin or a structurally similar analog, and norbaeocystin, respectively, for treating a neurological or psychological disorder is claimed by the inventors from the University of Miami [95]. Recent studies have suggested that microdosing the hallucinogenic drugs psilocybin and psilocin, belonging to the mushroom genus Psilocybe, resulted in greater improvements in the mental health of individuals by acting via 5-HT2A serotonin receptors, and can be a new treatment option for depression. While Psilocybin itself is not psychoactive, the rapidly dephosphorylated derivative psilocin, formed upon ingestion in the mucosa by alkaline phosphatases and nonspecific esterases, causes the hallucinogenic effect as it is structurally similar and binds to over 15 human signaling serotonin-related receptors [96, 97]. Optimi Health Corp. has filed two patents wherein a transdermal pharmaceutical composition comprising psilocybin and psilocin from Psilocybe mushrooms in deep eutectic solvent is claimed for the treatment of anxiety, depression, and other mental health conditions [98, 99]. In another patent, the assignee Mydecine Innovations Group Inc. has claimed a pharmaceutical composition comprising the combination of the serotonin receptor agonist psychedelic compound psilocybin, along with a suitable uridine 5'-diphospho-glucuronosyltransferase (UGT) inhibitor for not only inhibiting the metabolic breakdown and clearance of psilocin by glucuronidation, but also modulating the physiological response of the psychedelic compound in the subject [100]. Two patents assigned to Korea University Industrial & Academic Collaboration Foundation have claimed antidepressant compositions containing ethanolic extract of Pleurotus eryngii as an active ingredient. The extract has been shown to inhibit the binding of serotonin receptors with selective serotonin reuptake inhibitors in animal models, thereby activating signaling mediated by serotonin receptors to prevent depression [101, 102]. Pharmaceutical compositions comprising extracts of Poria cocos or dried Agaricus fruit bodies are also claimed for anti-depression activity [103, 104]. A composition comprising the bioactive compounds coralloicins A, B, and C isolated from the mushrooms Hericium coralloides or H. erinaceus for treating depression is claimed by Rembiotics [105]. Antidepressant compositions comprising serotonergic psychedelics from mushroom species including G. lucidum, H. erinaceus, C. sinensis, C. militaris, Cordyceps liangshanensis, Cordyceps gunnii, or Cordyceps cicadicola in combination with cannabinoids extracted from Cannabis sativa have been claimed for the treatment of psychosis and psychotic disorders [106]. Sichuan Edible Fungi Research Institute has claimed a method for preparing an enzyme-removed water extract of Flammulina velutipes mushroom containing γ-aminobutyric acid content of 0.15–1%, and its use in the preparation of an antidepressant product [107].

Anti-aging activity

Oxidative stress from reactive oxygen species can disturb the body’s natural mechanisms to fight harmful free radicals, causing accelerated aging and other medical complications such as ND and a decline in physiological function. Recent research has shown that the medicinal and edible mushroom species, namely G. lucidum, H. erinaceus, P. ostreatus, and A. bisporus containing bioactive ingredients such as carbohydrates, proteins, lipids, and phenolic compounds, possess the potential to combat the adverse impacts of skin aging while fortifying cellular health [108–110]. Nippon Menard Cosmetic Co. Ltd. has identified a highly safe supercritical, water and/or organic solvent extract of G. lucidum spores that has an excellent proliferation-promoting effect on stem cells, and hence can make a significant contribution in the field of anti-aging [111]. In another three patents, the assignee has demonstrated the neurogenesis, dermal, and hematopoietic stem cell differentiation action of the supercritical extract of G. lucidum spores which improves memory and learning associated with aging [112–114]. A Chinese patent jointly filed by Tongling Jieya Biologic Technology Co. Ltd. and Anhui University has claimed the preparation of Tremella aurantialba polysaccharide (TAP-W) and its use as a skin care substance that increases the content of skin collagen, and shows excellent tyrosinase inhibitory activity in ultraviolet-induced pigmentation in mouse skin [115]. A composition containing combined extracts of P. linteus and Tremella fuciformis in a mass ratio of (1–4):1 is claimed by Guangzhou EMG Biotech Co. Ltd. for the preparation of skin care products [116].

Musculoskeletal diseases

Pharmaceutical composition containing I. obliquus extract as an active ingredient for treating muscle diseases has been claimed by the assignee Phytomed. The mushroom ingredient increases the activity of mammalian target of rapamycin (mTOR), involved in muscle protein synthesis, and has an excellent effect in suppressing the mRNA expression of muscle-specific RING finger protein 1 (MuRF1) and atrogin-1, involved in muscle protein degradation. Additionally, being a natural pharmaceutical product, it can be safely used without side effects [117]. Grape King Bio. Ltd. has claimed that an extract of a fermented product of P. linteus and/or its derivative can improve sarcopenia and maintain the amount of muscular endurance [118]. Several medicinal mushroom genera have been shown to improve bone stability by influencing ossification, mineralization, and resorption [119]. Pharmaceutical compositions containing mushroom active ingredients such as P. linteus extract, T. fuciformis product fermented with lactic acid bacteria, or aqueous Auricularia auricula extract are claimed for preventing osteoporosis [120–122]. The A. auricular extract is shown to exhibit an anti-osteoporosis effect by simultaneously regulating differentiation of osteoclasts and osteoblasts involved in osteoporosis. Another pharmaceutical composition comprising L. edodes mushroom extract derived vitamin D2 as an active ingredient is claimed for promoting bone formation [123]. Jilin Agricultural University has claimed the method of extracting bioactive galactomannan from P. ostreatus useful for protecting myoblasts from oxidative damage and preparing protective muscle cells [124].

Anti-thrombotic activity

Anti-thrombotic attributes of different types of mushrooms have been reviewed, and it is shown that Ganoderma lucidium, Pleurotus giganteus, and A. auricula-judae possess encouraging anti-thrombotic activities [125]. Ten patents have claimed a pharmaceutical composition comprising extracts of different mushrooms, including T. fuciformis, Lentinus strigosus, Ganoderma gibbosum, G. lucidum, L. edodes, and P. linteus as active ingredients for preventing or treating various thrombotic diseases. In two patents filed jointly by Kyungpook National University Ind Academic Coop Foundation and Industrial Cooperation Foundation Jeonbuk National University, the inventors demonstrated that the alcoholic extract of T. fuciformis mushroom, and 6-hydroxy-2,2-dimethyl-3-chromen isolated from Panus rudis can effectively treat various thrombotic diseases by inhibiting platelet aggregation and thrombus formation, inhibiting calcium ion mobilization, platelet granule secretion, while releasing adenosine triphosphate (ATP) following collagen stimulation [126, 127]. In another four patents, the inventors have claimed pharmaceutical compositions comprising extracts of mushrooms like G. gibbosum, G. lucidum, L. edodes, and P. linteus, which exhibit strong antithrombotic and anticoagulant activity by inhibiting thrombosis-related enzymes, thus improving blood circulation [128–131]. Subcritical water GLE has also been claimed for promoting the differentiation of a hematopoietic stem cell into a blood cell, thus providing immunity among the elderly, and preventing hematopoietic diseases such as anemia, neutropenia, and thrombocytopenia [132]. A. bisporus polysaccharide extract composed of galactose (6-galactose, 2,6-galactose, T-galactose, and 3,6-galactose), T-fucose, 6-mannose, and glucose has been claimed to have an ameliorating effect on atherosclerosis by reducing the blood fat levels and improving inflammatory response and oxidative stress as demonstrated in mice [133]. Fujian University of Traditional Chinese Medicine has claimed a polyherbal pharmaceutical composition comprising 8–14 parts each of Antrodia camphorata, Dilong, and Angelica dahurica, and 4–8 parts licorice for promoting angiogenesis and treating cerebral apoplexy and ischemic cerebral stroke [134]. An Indian application filed by Shoolini University of Biotechnology and Management Sciences has studied the haemostatic properties of wild Irpex lacteus mushroom methanolic extract showing positive pro-coagulation time and vasoconstriction properties in vitro testing [135].

Lifestyle diseases

Lifestyle-related diseases, primarily hypertension and diabetes has increased remarkably in recent years. Furthermore, obesity is reported to cause these lifestyle-related diseases to develop and progress secondarily, and synergistically increase the risk of developing arteriosclerosis. The onset and progression of these lifestyle-related diseases and metabolic syndrome are closely related to dyslipidemia. Studies show that polysaccharides derived from the mushrooms P. ostreatus, Schizophyllum commune, Grifola rondosea, Sclerotium rolfsii, G. lucidum, L. edodes, and Hericium erunaceus have a therapeutic effect against metabolic syndrome, characterized by obesity, hypertension, and elevated blood sugar levels [136, 137]. Pharmaceutical composition containing a dry extract of I. obliquus with humic substances (4:1), such as humic and fulvic acids in a 73:27 weight ratio, is claimed for treating metabolic syndrome [138]. An additional three patents have also disclosed compositions comprising active mushroom ingredients such as mycelial culture of I. lacteus [139], P. cornucopia [140], and Ceriporia lacerate [141] for the treatment of metabolic diseases such as diabetes, improving lipid metabolism, and treating obesity. Inventors have demonstrated that the presence of 35.21% β-glucan, and 44.34% extracellular polysaccharides, based on the dry weight in mycelial extract of I. lacteus (KACC83046BP) reduces blood glucose levels, thus showing high industrial potential for the development of a natural material-based antidiabetic agent free of adverse effects. A solid or liquid pharmaceutical formulation comprising mycelia of L. edodes cultured for 5–10 days in a medium of barley and rice bran mixture is claimed for treating obesity. The inventors have further demonstrated that the mushroom extract suppressed the increase in liver weight by inhibiting fat accumulation in liver tissue in obese mouse model [142]. A composition containing an extract of the A. polytricha strain (KACC93319P) has been claimed to inhibit the differentiation of preadipocytes into adipocytes, and show excellent anti-obesity activity by inhibiting weight increase due to high fat diet, visceral fat accumulation, blood glucose level, low-density lipoprotein (LDL) cholesterol, and triglyceride accumulation [143]. Another PCT application has claimed a composition comprising an aqueous or ethanolic extract of one or more edible or medicinal mushrooms, along with one or more cannabinoids derived from ethanolic extract of C. sativa for treating obesity by promoting weight loss [144]. Beijing University of Chinese Medicine has claimed a traditional medicinal composition comprising chicory root, P. cocos, and rhizoma smilacis glabrae useful for treating diseases related to lipid metabolism disorders such as hyperlipidaemia, hypertriglyceridemia and/or low-density lipidaemia, and gastrointestinal dysfunction such as gastrointestinal absorption disorders, intestinal peristalsis disorders, constipation or diarrhea [145].

Anti-hepatitis activity

Scientists have examined the liver-protective effects of mushroom compounds to elucidate their role in hepatitis treatment [146]. Research suggests that tetramic acid-type compound (MCA17-1) from engineered Calcarisporium arbuscula can act as a potential liver fibrosis inhibitor [147]. More recently, AHCC, a standardized extract of cultured L. edodes mycelia has been shown to suppress hepatic fibrosis by inhibition of hepatic stellate cell activation [148]. Six patents claiming the treatment of liver fibrosis using mushroom material are discussed in this section. Two patents assigned to Cojet Biotech disclose the liver fibrosis treatment efficacy of the compound 5-methylbenzo[d][1,3]dioxole-4,7-diol (MBDD) derived from Antrodia cinnamomea extract by decreasing the activity of hepatic stellate cells [148–150]. The Academy of Military Medical Sciences has disclosed a hepatoprotective traditional Chinese medicine comprising GLE along with other herbal components that can be used as a vaccine adjuvant or an immunomodulator for treating liver injury, hepatitis, hepatic fibrosis, hepatic cirrhosis, or liver cancer [151]. Another Chinese patent has also claimed the use of GLE, spore oil, and polysaccharides in a complex injection formulation for protecting the liver [152]. A method for treating fatty liver disease caused by the intake of a high-fat diet is claimed by Novacell Technology Inc. by administering a pharmaceutical composition containing an effective amount of a powder or a mycelium of the hybrid mushroom Pleurotus spp. (GBN2WP0970) [153]. The active ingredient shows an excellent triglyceride absorption inhibitory effect without any adverse side effects. Fujian Agriculture & Forestry University has claimed a simple, economical, large-scale preparation method of a polypeptide from Volvariella volvacea showing antioxidant activity, hepatoprotective effect, and good inhibitory effect on alcoholic liver injury concluded through animal experiments [154].

Anti-addictive

Psychedelic-assisted therapy has shown promising results in the treatment for substance use disorders (SUDs) [155]. A total of three patents are included in this section, which indicate a beneficial effect of psilocybin-assisted therapy on drug addiction and opioid withdrawal through combined administration of Psilocybe and Cannabis-derived agents. A topical hydrogel analgesic comprising cannabinoids, menthol, and an effective amount of the active component psilocybin and/or psilocin extracted from the mushroom Psilocybe is claimed for treating drug addiction, particularly opioid addiction [156]. Another patent also claimed a composition comprising a combination of cannabinoids, terpenoids, herbs, and psychedelic compounds from a mushroom, such that the combined effect produces a superior therapeutic effect for alleviating opioid medicinal withdrawal symptoms [157]. A pharmaceutical herbal mixture comprising P. cocos, along with other herbs for treating alcohol hangover and associated conditions, is also claimed [158].

Pain management

Chronic pain is a major public health concern, primarily managed by conventional therapeutic agents, including opioid and non-opioid analgesics, which suffer from adverse side effects. Many psychedelic drugs extracted from mushrooms are being evaluated for their potential pain management activity through direct serotonin receptor agonism, anti-inflammatory effects, or synaptic changes [159]. Three patents are identified under this section that disclose the use of mushroom content in controlling different types of pain. A controlled release delivery system comprising polymeric spheres having the psychedelic compounds psilocybin and psilocin from the mushroom Psilocybe, encapsulated in a polymeric fibrous membrane, is claimed for treating fibromyalgia, chronic musculoskeletal pain, and other neuropathic pain [160]. The controlled release delivery system utilizing psychedelics is not only safe, but precise in the dosage and operates in a sustained and controlled dose manner. Another patent has claimed the use of Agaricus extract in a pharmaceutical composition for treating intestinal pain when administered at a dose of 60 mg–2.5 g daily via oral route [161]. Inventors have also claimed the use of Wolfiporia extract in developing a traditional Chinese medicinal composition for treating primary and secondary dysmenorrhea in women [162].

Spleen strength enhancer

Mushrooms containing bioactive ingredients have been claimed to modulate and increase spleen strength. Two Chinese patents have disclosed the use of Wolfiporia and P. cocos extract for regulating spleen deficiency [163, 164].

Respiratory disorders

Scientific studies have demonstrated the positive effects of G. lucidum spore and fruiting body on tobacco smoke carcinogen-induced lung toxicity and carcinogenesis [165]. In this section, two patents are highlighted for the same effect. In one patent, a method of treating chronic obstructive pulmonary disease (COPD) caused by emphysema or chronic bronchitis using a pharmaceutical composition comprising dried P. cocos in 20–80 wt% is claimed [166]. Another Chinese patent has claimed a composition comprising GLE including 8–20% triterpenes, and G. lucidum spore powder for inhibiting pulmonary fibrosis caused by radiation lung injury [167].

Miscellaneous patents

A single patent claiming a product comprising extracts or active compounds from one or more mushroom types or a method for the treatment of any specific condition or multiple conditions is grouped under this category. Nine patents [168–176] identified in this category were analyzed in Table 3 on the basis of the mushroom genus, extract or bioactive involved, and biological role per type of disorder as disclosed in the retrieved patents.