A review on the cultivation, bioactive compounds, health-promoting factors and clinical trials of medicinal mushrooms Taiwanofungus camphoratus, Inonotus obliquus and Tropicoporus linteus.

Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.

Evaluation of Ointments with Daldinia eschscholtzii in Wound Healing in an In Vivo Model.

Fungi are a source of a variety of secondary metabolites of importance in different areas of biotechnology. Several compounds have been characterized with antioxidant, antimicrobial, and anti-inflammatory activity from fungi of the division of the Ascomycota, among which is the species Daldinia eschscholtzii, an endophyte fungus of pantropical distribution. In this study, we evaluated the effect of an ointment made with D. eschscholtzii on the wound healing of BALB/c mice. The species was corroborated using a molecular marker Internal Transcribed Spacer (ITS1 and ITS4). The extracts and dust of the fungus were considered nontoxic as they caused a mortality of <15% in the nematode Panagrellus redivivus, and experimental ointments had no adverse effects on the skin of BALB/c mice. Wounds treated with the D. eschscholtzii ointments had 99.9-100% wound contraction after 17 days, which was similar to commercial healing (positive control). As such, the ointment of D. eschscholtzii is a natural alternative to improve wound healing.

Biological Characteristics, Domesticated Cultivation Protocol, Antioxidant Activity, and Protective Effects against Cellular Oxidative Stress of an Underutilized Medicinal Mushroom: Fomitopsis palustris.

Brown-rot fungus is one of the important medicinal mushrooms, which include some species within the genus Fomitopsis. This study identified wild macrofungi collected from a broad-leaved tree in Liaoning Province as Fomitopsis palustris using both morphological and molecular methods. To elucidate the potential medicinal and economic value of F. palustris, we conducted single-factor and orthogonal tests to optimize its mycelium culture conditions. Subsequently, we completed liquid culture and domestic cultivation based on these findings. Furthermore, crude polysaccharides were extracted from the cultivated fruiting bodies of F. palustris and their antioxidant activity was evaluated using chemical methods and cell-based models. The results showed that the optimal culture conditions for F. palustris mycelium were glucose as the carbon source, yeast extract powder as the nitrogen source, pH 6.0, and a temperature of 35 °C. Moreover, temperature was found to have the most significant impact on mycelial growth. The liquid strains were fermented for 6 days and then inoculated into a cultivation substrate composed of broadleaf sawdust, resulting in mature fruiting bodies in approximately 60 days. The crude polysaccharides extracted from the cultivated fruiting bodies of F. palustris (FPPs) possess in vitro scavenging abilities against DPPH radicals and OH radicals, as well as a certain ferric-reducing antioxidant power. Additionally, FPPs effectively mitigated H2O2-induced oxidative stress in RAW264.7cells by enhancing the intracellular activity of antioxidant enzymes such as SOD and CAT, scavenging excess ROS, and reducing MDA levels. This study provides preliminarily evidence of the potential medicinal and economic value of F. palustris and offers initial data for the future development and utilization of this species.

Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review.

Inonotus obliquus, also known as Chaga, is a medicinal mushroom that has been used for therapeutic purposes since the sixteenth century. Collections of folk medicine record the application of Chaga for the treatment of diseases such as gastrointestinal cancer, diabetes, bacterial infection, and liver diseases. Modern research provides scientific evidence of the therapeutic properties of I. obliquus extracts, including anti-inflammatory, antioxidant, anticancer, anti-diabetic, anti-obesity, hepatoprotective, renoprotective, anti-fatigue, antibacterial, and antiviral activities. Various bioactive compounds, including polysaccharides, triterpenoids, polyphenols, and lignin metabolites have been found to be responsible for the health-benefiting properties of I. obliquus. Furthermore, some studies have elucidated the underlying mechanisms of the mushroom's medicinal effects, revealing the compounds' interactions with enzymes or proteins of important pathways. Thus, this review aims to explore available information on the therapeutic potentials of Inonotus obliquus for the development of an effective naturally sourced treatment option.

Biological Activities of Ethanol Extracts of Hericium erinaceus Obtained as a Result of Optimization Analysis.

Mushrooms are one of the indispensable elements of human diets. Edible mushrooms stand out with their aroma and nutritional properties. In this study, some biological activities of the wild edible mushroom Hericium erinaceus were determined. In this context, firstly, the most suitable extraction conditions of the fungus in terms of biological activity were determined. First, 64 different experiments were performed with the Soxhlet device under 40-70 °C extraction temperature, 3-9 h extraction time, and 0.5-2 mg/mL extraction conditions. As a result, a total antioxidant status (TAS) analysis was performed, and the extraction conditions were optimized so that the objective function was the maximum TAS value. The data obtained from the experimental study were modeled with artificial neural networks (ANNs), one of the artificial intelligence methods, and optimized with a genetic algorithm (GA). All subsequent tests were performed using the extract obtained under optimum extraction conditions. The antioxidant capacity of the mushroom was assessed using Rel assay kits and the DPPH and FRAP techniques. The agar dilution method was used to measure the antimicrobial activity. The anti-Alzheimer activity was assessed based on the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The antiproliferative activity was assessed against the A549 cancer cell line. The total phenolic content was measured using the Folin-Ciocalteu reagent. The measurement of total flavonoids was conducted using the aluminum chloride test. LC-MS/MS equipment was used to screen for the presence of standard chemicals. The optimum extraction conditions were found to be a 60.667 °C temperature, 7.833 h, and 1.98 mg/mL. It was determined that the mushroom has high antioxidant potential. It was determined that the substance was successful at combating common bacterial and fungal strains when used at dosages ranging from 25 to 200 µg/mL. The high antiproliferative effect of the substance was attributed to its heightened concentration. The anti-AChE value was found to be 13.85 µg/mL, while the anti-BChE value was confirmed to be 28.00 µg/mL. The phenolic analysis of the mushroom revealed the presence of 13 chemicals. This investigation found that H. erinaceus exhibits robust biological activity when extracted under appropriate circumstances.

The Effect of Green Extraction Technologies on the Chemical Composition of Medicinal Chaga Mushroom Extracts.

The mushroom industry should implement green extraction technologies; however, there is not enough information on the differences between these techniques expressed as the chemical composition of the resulting extract. In this study, selected types of green extraction techniques (GETs) were used on Chaga (Inonotus obliquus) (Fr.) Pilát from Serbia (IS) and Mongolia (IM) to examine the differences that would enable the composition-based technology choices in the mushroom supplement industry. Subcritical water extraction (SWE), microwave-assisted (MW) extraction, and ultrasonic-assisted extraction (VAE) were used to prepare the extracts. SWE was performed at two different temperatures (120 and 200 °C), while 96% ethanol, 50% ethanol, and water were used for MW and VAE. The yield, the content of total phenols, total proteins, and carbohydrates, qualitative and quantitative analysis of phenolic compounds, carbohydrates, including α- and ß- and total glucans, and fatty acids, were determined in the obtained extracts. SWE resulted in a significantly higher yield, total polysaccharide, and glucan content than any other technique. Glucose was the most dominant monosaccharide in the SWE samples, especially those extracted at 200 °C. The MW 50% EtOH extracts showed the highest yield of total phenols. Among the tested phenolic compounds, chlorogenic acid was the most dominant. SWE can be recommended as the most efficient method for extracting commercially important compounds, especially glucans and phenols.

A novel method for detecting conformation-dependent ß-glucans-single, double, and triple-helical from Shiitake mushroom.

This pioneering study explores the structural intricacies of therapeutic ß-glucan in Shiitake (Lentinula edodes), i.e. Lentinan (LNT). Lentinan, a neutral polysaccharide [ß-(1,3; 1,6) glucan], exists in three forms; single, double, and triple-helical, but conformation-dependent bioactivity studies are lacking. In this context, we meticulously assessed indigenous Shiitake accessions from Northeast India, unveiling the conformational spectrum of LNT through an innovative pipeline. The experiment approached the simultaneous estimation of total glucan (TG), triple helical glucan (THG), and single-double helical glucan (SDG). Profiling revealed the exceptional LNT content in DMRO-623 (TG: 46.74%, SDG: 9.34%, THG: 37.39%) which emerged as the highest documented to date. Beyond the culinary delight, this research and the novel approach to LNT quantification will create a pivotal platform for advanced mushroom research, offering prospects for novel discoveries, innovative applications, and therapeutic potential.

Bioactivity and Metabolomic Profile of Extracts Derived from Mycelial Solid Cultures of Hypsizygus marmoreus.

The beech mushroom (Hypsizygus marmoreus) is a highly nutritious, edible medicinal mushroom native to East Asia. The present research investigated the impact of different substrates on the metabolite compositions of H. marmoreus mycelia cultivated in vitro. The substrates tested included malt extract agar, malt extract agar enriched with barley malt, and malt extract agar enriched with grape pomace. The study also assessed antimicrobial and antiradical activities of the extracts against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa), yeasts (Candida albicans, C. tropicalis, and C. parapsilosis), and dermatophytes (Trichophyton mentagrophytes, T. tonsurans, T. rubrum, Arthroderma quadrifidum, A. gypseum, A. curreyi, and A. insingulare). The results revealed that the H. marmoreus mycelia extracts demonstrated antibacterial and antifungal activities against the tested microorganisms. Extracts obtained from the cultivation in substrates enriched with either barley malt or grape pomace exhibited the highest antibacterial activity among all the tested bacterial strains except for P. aeruginosa. The same extracts showed the highest inhibitory effect against C. albicans and C. parapsilosis. Noteworthy, the extract from the mushroom cultivated in the substrate enriched with grape pomace also exhibited remarkable efficacy against T. mentagrophytes and T. tonsurans. Terpenoid and carbapenem compounds could be related to the antimicrobial properties of the extracts from mushrooms cultivated in substrates enriched with grape pomace. In comparison, the higher antiradical properties could be related to the content of indole compounds. In conclusion, growth substrate selection affects the nutritional and medicinal properties of H. marmoreus, making it a valuable contribution to the understanding of the cultivation of this mushroom.

Potentialities of Ganoderma lucidum extracts as functional ingredients in food formulation.

Owing to the recognized therapeutic characteristics of G. lucidum, it is one of the most extensively researched mushrooms as a chemopreventive agent and as a functional food. It is a known wood-degrading basidiomycete possessing numerous pharmacological functions and is termed a natural pharmacy store due to its rich number of active compounds which have proved to portray numerous therapeutic properties. This current review highlights studies on the potentialities of G. lucidum extracts as functional ingredients on organoleptic and nutritional properties of food products (e.g., dairy, wine, beverage, bakery, meat, and other products). In addition, the study delved into various aspects of encapsulated G. lucidum extracts, their morphological and rheological characteristics, prebiotic and immunomodulatory importance, the effects on apoptosis, autophagy, cancer therapy, inflammatory responses, oxidative stress, antioxidant activities, and safety concerns. These findings have significant implications for the development of new products in the food and pharmaceutical industries. On the other hand, the various active compounds extracted from G. lucidum exhibited no toxic or adverse effects, and the appeal for it as a dietary food, natural remedy, and health-fortifying food is drastically increasing as well as attracting the interest of both the industrial and scientific communities. Furthermore, the formation of functional foods based on G. lucidum appears to have actual promise and exciting prospects in nutrition, food, and pharmaceutical sciences.

Neuroprotective Effects of Sparassis crispa Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells.

Sparassis crispa, known as the "Cauliflower mushroom", is an edible medicinal fungus found in Asia, Europe, and North America. Its fruiting bodies contain active biological and pharmacological ingredients with antitumor and anti-inflammatory properties. In this study, we investigated the neuroprotective effect of various Sparassis crispa extract against glutamate-induced toxicity and oxidative stress in hippocampal HT22 cells. Cell viability and reactive oxygen species (ROS) analyses served to evaluate the neuroprotective effects of Sparassis crispa ethanol extract (SCE) and their fractions partitioned with ethyl acetate (EtOAc; SCE-E) and water (SCE-W) in HT22 cells. SCE and SCE-E treatment reduced glutamate-induced cell death and ROS generation. SCE-E reduced apoptosis and ROS levels by regulating anti-apoptotic proteins. Under glutamate treatment, SCE-E activated nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and regulated extracellular signal-regulated kinase (ERK) and AKT signals at late stages. SCE-E increased the protein expression of cAMP response element binding (CREB), brain-derived neurotrophic factor (BDNF), and Kelch-like ECH-associated protein 1 (Keap1), and decreased the Nrf2 protein expression. Moreover, co-treatment of SCE-E and wortmannin did not activate Nrf2 expression. Thus, the neuroprotective effect of SCE-E is likely due to Nrf2 and CREB activation through AKT and ERK phosphorylation, which effectively suppress glutamate-induced oxidative stress in HT22 cells. Accordingly, a daily supplement of SCE-E could become a potential treatment for oxidative-stress-related neurological diseases.

Mixed Medicinal Mushroom Mycelia Attenuates Alzheimer's Disease Pathologies In Vitro and In Vivo.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-ß (Aß) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM)-Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus-cultivated on a barley medium was assessed for its anti-AD effects. Neuron-like PC12 cells, which were subjected to Zn2+, an Aß aggregator, were employed as an in vitro AD model. The cells pretreated with or without MMMM were assayed for Aß immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. Then, 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aß immunofluorescence, ROS accumulation, and apoptosis, and incrementation in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aß plaque accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aß plaque accumulation and neuroinflammation, by impeding Aß-induced neurotoxicity.

Transcriptome and Metabolome Integration Reveals the Impact of Fungal Elicitors on Triterpene Accumulation in Sanghuangporus sanghuang.

Sanghuangporus sanghuang is a large wood-decaying mushroom highly valued in traditional Chinese medicine due to its medicinal properties, including hypoglycemic, antioxidant, antitumor, and antibacterial properties effects. Its key bioactive compounds include flavonoids and triterpenoids. Specific fungal genes can be selectively induced by fungal elicitors. To investigate the effect of fungal polysaccharides derived from Perenniporia tenuis mycelia on the metabolites of S. sanghuang, we conducted metabolic and transcriptional profiling with and without elicitor treatment (ET and WET, respectively). Correlation analysis showed significant differences in triterpenoid biosynthesis between the ET and WET groups. In addition, the structural genes associated with triterpenoids and their metabolites in both groups were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Through metabolite screening, three triterpenoids were identified: betulinol, betulinic acid, and 2-hydroxyoleanolic acid. Excitation treatment increased the level of betulinic acid by 2.62-fold and 2-hydroxyoleanolic acid by 114.67-fold compared to WET. The qRT-PCR results of the four genes expressed in secondary metabolic pathways, defense gene activation, and signal transduction showed significant variation between the ET and WET groups. Overall, our study suggests that the fungal elicitor induced the aggregation of pentacyclic triterpenoid secondary metabolites in S. sanghuang.

Mycochemicals against Cancer Stem Cells.

Since ancient times, mushrooms have been considered valuable allies of human well-being both from a dietary and medicinal point of view. Their essential role in several traditional medicines is explained today by the discovery of the plethora of biomolecules that have shown proven efficacy for treating various diseases, including cancer. Numerous studies have already been conducted to explore the antitumoural properties of mushroom extracts against cancer. Still, very few have reported the anticancer properties of mushroom polysaccharides and mycochemicals against the specific population of cancer stem cells (CSCs). In this context, ß-glucans are relevant in modulating immunological surveillance against this subpopulation of cancer cells within tumours. Small molecules, less studied despite their spread and assortment, could exhibit the same importance. In this review, we discuss several pieces of evidence of the association between ß-glucans and small mycochemicals in modulating biological mechanisms which are proven to be involved with CSCs development. Experimental evidence and an in silico approach are evaluated with the hope of contributing to future strategies aimed at the direct study of the action of these mycochemicals on this subpopulation of cancer cells.

Chemical Characterization and Evaluation of Antimicrobial Properties of the Wild Medicinal Mushroom Ganoderma lucidum Growing in Northern Moroccan Forests.

Ganoderma lucidum is an extensively famous medicinal mushroom distributed worldwide. Despite being widely grown in Moroccan forests, there are no studies on its nutritional, nutraceutical and pharmaceutical values. Herein, the objective of this study was to investigate the chemical characterization and antimicrobial properties of G. lucidum methanolic extract. Total phenolic, flavonoid, tannin, ascorbic acid and carotenoid contents were determined by spectrophotometry. The results revealed that the most prevalent bioactive compounds were phenolics and flavonoids, with total values of 154.60 mg GAE/g of dry methanolic extract (dme) and 60.55 mg CE/mg of dme, respectively. A GC-MS analysis identified 80 biologically active molecules, which were mainly divided into the following major groups: sugars (49.49%), organic acids (8.89%), fatty acids (7.75%), amino acids (7.44%), steroids (7.32%), polyphenols (5.92%), and others (13.16%). Additionally, 22 individual phenolic compounds were identified and quantified using HPLC-MS, with emphasis on kaempferol (1714 µg/g of dry weight (dw)), apigenin (1955 µg/g dw) and quercetin (947.2 µg/g dw). The methanolic extract of G. lucidum indicated strong antioxidant capacity by means of the following: DPPH radical-scavenging activity (53.7 µg/mL), ß-carotene/linoleate assay (43.75 µg/mL), and reducing power assay (76.62 µg/mL). Furthermore, the extract exhibited potent antimicrobial properties against seven human pathogenic microorganisms, including two bacteria and five fungal strains, at concentrations ranging from 1 to 16 mg/mL. The most sensitive pathogen was Epidermophyton floccosum (MIC = MFC = 1 mg/mL), while Aspergillus fumigatus was the most resistant one (MIC = 16 mg/mL and MFC ≥ 16 mg/mL). Overall, our findings demonstrated valuable nutritional and bioactive compound attributes, and potent antioxidant and antimicrobial properties, of G. lucidum growing in Moroccan forests. Moreover, these findings suggest that the Moroccan mushroom can be extremely useful for the food and medicinal industries to positively affect socioeconomic status.

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review.

Cancer is the leading cause of mortality globally. With anticancer medications causing severe adverse effects, understanding the role of alternative and efficacious anticancer treatments with minimal or no side effects can be beneficial. Edible mushrooms have been associated with certain health benefits and exhibit a broad range of pharmacological activities, including anti-inflammatory and immunomodulating activities. The anticancer potential of different mushrooms is now being tested. The goal of this scoping review was to discuss the most recent and available evidence on the therapeutic uses of medicinal mushrooms in cancer treatment, specifically those cancers with some of the highest mortality rates (i.e., gastric, breast, and colorectal cancer). Randomly controlled trials, clinical trials, and retrospective cohort studies (with placebo group) with human subjects published between 2012-2023 were searched using the databases Embase, Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL), and Alt HealthWatch. The initial search yielded 2,202 articles. After removing 853 duplicate citations, 1,349 articles remained and were screened for study eligibility and accessibility, leaving 26 articles. The inclusion and exclusion criteria were then used to assess the remaining 26 full-text articles and nine articles were selected for the final review. The characteristics of the nine studies reported the efficacy of medicinal mushrooms Lentinus edodes (Shiitake), Coriolus versicolor (Turkey Tail), and Agaricus Sylvaticus (Scaly Wood), in treating symptoms, medication side effects, anti-tumor effects, and survival outcomes in gastric, breast, and colorectal cancers. Findings from this review suggest that medicinal mushrooms have the potential to prevent lymph node metastasis, prolong overall survival, decrease chemotherapy-induced side effects (e.g., diarrhea, vomiting), affect the immune system, and help maintain immune function and quality of life in patients with certain cancers. More research is needed with human subjects using RCTs with larger samples to ensure accurate outcomes and ascertain the most efficacious dosages.

Evaluation of phytochemicals of Poria cocos against tyrosinase protein: a virtual screening, pharmacoinformatics and molecular dynamics study.

Tyrosinase inhibitors are commonly used in the pharmaceutical and cosmetic industries for skin lightening and hypopigmentation. The current inhibitors of tyrosinase induce strong safety concerns which necessitate the discovery of new inhibitors. Natural compounds are a promising solution to discover potential candidate for anti-melanogenic activity as they possess less safety concerns and high therapeutic effect. The current study aimed to screen and identify potential phytochemicals from Poria cocos for tyrosinase inhibition. The phytochemicals were obtained from the Traditional Chinese Medicine System Pharmacology Database and screened for druglikeness score and toxicity class and then subjected to in-silico virtual screening and molecular dynamics. 7,9-(11)-Dehydropachymic acid established hydrogen interaction with the tyrosinase protein and was found to be highly stable as validated with MD simulations. The pharmacokinetic results showed that this compound has adequate toxicity and ADME profile that can be exploited for anti-melanogenic effects. Our study identified 7,9-(11)-dehydropachymic acid as an efficient candidate for tyrosinase inhibition. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03626-8.

Fungi as a source of bioactive molecules for the development of longevity medicines.

Age-related loss of function brings age-related disease, and therefore it is of primary importance to search for interventions that can help minimize detrimental symptoms people deal with in old age. Fungi have always been given a great deal of attention and reverence in traditional medical practices for their ability to minimize harmful symptoms of diseases. More recently, the role of fungi in influencing healthspan and lifespan is being directly studied in the lab. To treat animal model organisms with fungi-derived molecules, extractions from different life cycle stages of fungi are performed. This includes mycelium (the vegetative stage), sporocarps (the reproductive stage), or spores (the end product of the reproductive stage), and each stage provides a variety of bioactive compounds. These bioactive compounds include glycoproteins, polysaccharides, triterpenoids, meroterpenoids, sesquiterpenoids, steroids, alkaloids, benzopyran derivatives, and benzoic acid derivatives, amongst others. In this work, we review evidence that fungal extracts from multiple species can have beneficial effects on the lifespan and healthspan of model organisms, such as C. elegans worms, D. melanogaster flies, and M. musculus mice. We cover extraction methods and lifespan effects of Ganoderma lucidum (i.e. Reishi), Lentinula edodes (i.e. Shiitake), the genus Auricularia (i.e. jelly ear mushrooms), the genera Cordyceps and Ophiocordyceps (e.g. the caterpillar fungi), Hericium erinaceus (i.e. Lion's mane), the mold genus Monascus, and also Inonotus obliquus (i.e. Chaga), Grifola frondosa (i.e. Maitake or hen-of-the-woods), the genus Pleurotus (e.g. oyster mushrooms), and Agaricus subrufescens (i.e. the almond mushroom). We propose that further research on fungal extracts will provide a greater picture of the role fungi-derived bioactive molecules can have in developing longevity and neuroprotective medicines for humans.

Secondary Metabolites of Bird's Nest Fungi: Chemical Structures and Biological Activities.

Bird's nest fungi, a general term for species in the family Nidulariaceae, are named for their fruiting bodies that resemble bird's nests. Two of their members, Cyathus stercoreus (Schw.) de Toni. and Cyathus striatus Will. ex Pers., are known as medicinal fungi in Chinese medicine. Bird's nest fungi produce a variety of secondary metabolites that provide natural materials for screening and developing medicinal compounds. This review presents a systematic summary of the literature on the secondary metabolites of bird's nest fungi up to January 2023, including 185 compounds, mainly cyathane diterpenoids, with prominently characterized antimicrobial and antineurodegenerative activities. Our work aims to advance our understanding of bird's nest fungi and support studies on their natural product chemistry, pharmacology, and biosynthesis of secondary metabolites.

Identification of galacturonic acid-rich polysaccharide with intestinal immune system modulating activity via Peyer's patch from postbiotics of Phellinus linteus mycelial submerged culture.

Interests in the development and exploration of industrial applications of medicinal mushrooms as postbiotics have lately increased. We recently reported the potential use of Phellinus linteus mycelial-containing whole culture extract (PLME) prepared by submerged cultivation as a postbiotic that promotes immune system activation. Here, we aimed to isolate and structurally elucidate the active ingredients in PLME by activity-guided fractionation. The intestinal immunostimulatory activity was evaluated by bone marrow (BM) cell proliferation activity and related cytokine production in C3H-HeN mouse-derived Peyer's patch (PP) cells treated with polysaccharide fractions. The initially crude polysaccharide (PLME-CP) of PLME prepared using ethanol precipitation was further fractionated into four fractions (PLME-CP-0 to -III) by anion-exchange column chromatography. BM cell proliferation and cytokine production of PLME-CP-III were significantly improved compared to those of PLME-CP. PLME-CP-III was then fractionated into PLME-CP-III-1 and PLME-CP-III-2 by gel filtration chromatography. Based on the molecular weight distribution, monosaccharide, and glycosyl linkage analyses, PLME-CP-III-1 was revealed as a novel galacturonic acid-rich acidic polysaccharide and further shown to play an important role in facilitating PP-mediated intestinal immunostimulatory activity. This is the first study demonstrating the structural characteristics of a novel intestinal immune system modulating acidic polysaccharide from P. linteus mycelium-containing whole culture broth postbiotics.

Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract.

Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. The most affected cognitive function is memory, worsening early during aging. Inflammation and oxidative stress are known to have a role in pathogenesis of cognitive impairments, and a link exists between aging/frailty and immunosenescence/inflammaging. Based on anti-aging properties, medicinal mushrooms represent a source to develop medicines and functional foods. In particular, Hericium erinaceus (He) displays several actions ranging from boosting the immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, we demonstrated the efficacy of an ERGO-rich He primordium extract (He2) in preventing cognitive decline in a murine model of aging. We focused on recognition memory deterioration during aging, monitored through spontaneous behavioral tests assessing both memory components and frailty index. A parallel significant decrease in key markers of inflammation and oxidative stress, i.e., IL6, TGFß1, GFAP, Nrf2, SOD1, COX2, NOS2, was revealed in the hippocampus by immunohistochemistry, accompanied by an enhancement of NMDAR1and mGluR2, crucially involved in glutamatergic neurotransmission. In summary, we disclosed a selective, preventive and neuroprotective effect of He2 on aged hippocampus, both on recognition memory as well on inflammation/oxidative stress/glutamate receptors expression.