This study was conducted to evaluate the effects of topical application of aqueous extract of Hericium erinaceus fruiting bodies (HEFB) on the rate of wound healing enclosure and histology of the healed wound. Five groups of male Sprague-Dawley rats were experimentally wounded in the posterior neck area. A uniform wound area of 2.00 cm in diameter, using a circular stamp, was excised from the nape of the dorsal neck of all rats with the aid of a round seal. The animal groups were topically treated, respectively, with 0.2 mL each of sterilized distilled water (sdH2O); Intrasite gel; and 20, 30, and 40 mg/mL HEFB. Macroscopically, those rats whose wounds were dressed with HEFB and those in the Intrasite gel-treated group healed earlier than those treated with sdH2O. Histological analysis of healed wounds dressed with HEFB showed less scar width at wound enclosure and the healed wound contained fewer macrophages and more collagen with angiogenesis, compared to wounds dressed with sdH2O. In conclusion, wounds dressed with HEFB significantly enhanced the acceleration of wound healing enclosure in rats.
This study evaluated the in vitro antioxidant capacities of extracts from Pleurotus pulmonarius via Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, metal chelating, cupric ion reducing antioxidant capacity, and lipid peroxidation inhibition assays. Extract compositions were determined by phenol-sulfuric acid; Coomassie Plus (Bradford) protein; Spectroquant zinc, copper, and manganese test assays; and liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). Methanol-dichloromethane extract, water fraction, hot water, aqueous extract and hexane fraction exhibited the most potent extracts in the antioxidant activities. LC/MS/MS and GC/MS showed that the extracts contained ergothioneine, ergosterol, flavonoid, and phenolic compounds. The selected potent extracts were evaluated for their inhibitory effect against oxidation of human low-density lipoproteins and protective effects against hydrogen peroxide-induced cytotoxic injury in human aortic endothelial cells. The crude aqueous extract was deemed most potent for the prevention of human low-density lipoprotein oxidation and endothelial membrane damage. Ergothioneine might be the compound responsible for the activities, as supported by previous reports. Thus, P. pulmonarius may be a valuable antioxidant ingredient in functional foods or nutraceuticals.
This study evaluates the in vitro inhibition of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) by Pleurotus pulmonarius extracts. The protective effect on the endothelial membrane against oxidative stress through the protection of nitric oxide bioavailability, as well as inhibition of endocan expression, was evaluated using human aortic endothelial cells (HAECs). Crude cold aqueous extract exhibited the most potent inhibitory activities against ACE and HMG-CoA reductase, with 61.79% and 44.30% inhibition, respectively. It also protected the bioavailability of NO released by HAECs, with 84.88% cell viability. The crude hot water extract was the most potent in inhibiting endocan expression, with 18.61% inhibition.
Lentinus edodes (shiitake mushroom) has exhibited fibrinolytic activity. We synthesized and characterized selenium nanoparticles (SeNPs) using protein precipitated from the mushroom. We also investigated the fibrinolytic activity of the SeNPs. The proteins from a crude extract of L. edodes were recovered through the use of aqueous 2-phase separation, and these we used as the capping agent in SeNP biosynthesis. We characterized the SeNPs using UV-visible spectrophotometry, field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), particle size distribution analysis, and Fourier transform infrared spectroscopy (FT-IR). The fibrinolytic capability of the SeNPs was tested through an in vitro fibrin plate assay. The UV-visible spectra showed maximal absorbance at 220 nm. FESEM images showed that the SeNPs were dispersed and did not clump. The TEM images revealed a spherical shape and average size of the SeNPs. The particle size distribution analysis confirmed the mean size of the SeNPs at 64.53 nm. A strong signal for the presence of selenium was observed in the EDX analysis. The FT-IR spectrum revealed the involvement of protein functional groups in the reduction of sel-enite. Overall, the SeNPs capped with protein from shiitake mushroom were effective as an in vitro fibrinolytic agent.
COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.
The research field of culinary and medicinal mushrooms has been well developed since the first relevant publication in 1966. However, to date, there has been no bibliometric analysis published specifically for this field. This study aimed to assess the most influential publications as well as the research trends and important drivers in the field of culinary and medicinal mushrooms. Scopus was used to identify relevant publications and the 1000 most-cited publications were identified and analyzed. Bradford's law of scattering shows one-third of the papers were published in 14 core journals, with a total of 102 papers published in International Journal of Medicinal Mushrooms. There is an insignificant negative correlation (Pearson's correlation coefficient, r = -0.355) between the journal impact factor and publication count. VOSviewer was used to generate a country network. China represents Asia's research center in this field, having contributed 20% of the 1000 most-cited publications. A term map was also created to visualize the co-occurrence of key terms in the domain. Different biological activities such as antioxidant and antitumor properties of mushrooms appeared to be a recurring topic in this field. Wasser (2003) showed the highest citation count (n = 1282), which is almost double the second most-cited publication (n = 611). There is a weak positive correlation (r = +0.237) between the years since publication and total citation count. In conclusion, this bibliometric study will assist researchers to comprehend the current status of the research on culinary and medicinal mushrooms, and to visualize the future impact of such an important field.
In this study, crude extracts of Ganoderma lucidum (NGCs) were compared to the crude extracts of G. lucidum that has antler-like fruiting bodies (AGCs) for their cytotoxicity, inhibitory effects on the attachment of human immunodeficiency virus (HIV)-1 glycoprotein 120 (gp120) to cluster of differentiation 4 (CD4), identification and molecular docking simulations of chemical compounds to predict the best ligand inhibitor and the binding mechanism. Results showed that AGCs had a higher percentage of inhibition (54.3% ± 6.2%) at 150 ppm and higher cytotoxicity (half maximal cytotoxic concentration [CC50] < 300 ppm) than NGCs (CC50 < 400 ppm). Quadrupole time-of-flight (QTOF) liquid chromatography- mass spectrometry (LC-MS) results successfully identified 32 chemical compounds in AGCs and NGCs, comprising mostly ganoderic acids (62%) and their derivatives. Molecular docking simulations of ganolucidic acid A/D and ganoderic acid A/B predicted the strongest binding affinity via hydrogen bonding, suggesting the inhibition of HIV-1 gp120 attachment to CD4. The highest and lowest occupied molecular orbital (HOMO and LUMO, respectively) gap energies of ganoderic acids tended to have less negative HOMO energy and smaller HOMO-LUMO gap energy, implying increased interactions of ligands to the gp120 protein receptor. AGCs showed higher inhibition against HIV-1 gp120 than NGCs due to a higher abundance of ganoderic and ganolucidic acids, whereby both acids contributed the highest number of hydrogen bonds and polar interactions from the hydroxyl and carboxylic functional groups.
Spaceflight represents a complex environmental condition. Space mutagenesis breeding has achieved marked results over the years. The objective of this study is to determine the chemical changes in medicinal mushroom Ganoderma lucidum cultivated after spaceflight in 1999. Fourier transform infrared (FTIR) and two-dimensional infrared (2DIR) correlation spectroscopy were used in analysis. The sample Sx and its control Cx showed the least dissimilarities in one-dimensional FTIR spectra, but absorbance of Sx is twice as high as Cx. Sx presented a clear peak at 1648 cm in 2nd derivative spectra, which could not be detected in the Cx. The 2DIR spectra showed the intensity of Sx in the range 1800-1400 cm-1 for protein is higher than the control. The sample Sx produced some carbohydrate peaks in the area of 889 cm-1 compared with the Cx. The spaceflight set up an extreme condition and caused changes of chemical properties in G. lucidum strain.
A cultivar of fruiting bodies of Ophiocordyceps sinensis (FBOS; OCS02) was analyzed for nutrients, bioactive compounds, and heavy metal content to showcase its potential as a competitive, sustainable, and safe alternative to wild types and other cultivars. A previous 28-day subacute toxicity study showed that doses up to 1 g · kg-1 did not cause any adverse effects in Sprague-Dawley rats. The OCS02 cultivar contained large amounts of cordycepin, polysaccharides, and essential and semi-essential amino acids (0.66, 482.80, 99.02, and 101.04 g · kg-1, respectively) compared with levels reported in wild types and in cultivated mycelia. β-1,3/1,6-glucan content was considerably high at 342.50 g · kg-1. The potassium level (5.14 g kg-1) tied in well with the low sodium content (0.121 g · kg-1)-6 times lower than amounts in wild types. We found no detectable levels of heavy metals such as lead, arsenic, cadmium, and mercury. The major amino acids found in FBOS (0CS02 cultivar) were arginine, lysine, serine, and threonine at 45.20, 20.30, 18.60, and 18.20 g · kg-1, respectively. The cultivated FBOS (OCS02 cultivar) is a comparable alternative to wild-type and other cultivated strains of O. sinensis. It has potential as a nutraceutical to meet market demand.
Amauroderma rugosum is a wild medicinal mushroom also known as budak cendawan sawan. Members of the indigenous Malaysian Temuan community wear the fresh stipes as a necklace to prevent epileptic seizure and unremitting crying by babies. In our previous studies, A. rugosum exhibited significant antioxidant and anti-inflammatory activities. The aim of this study was to determine the toxicity (in the event that a stipe is accidentally bitten) and cytotoxicity of this mushroom on Sprague-Dawley rats and selected cell lines. A. rugosum was orally administered to test chemicals according to Organisation for Economic and Co-operation and Development guidelines (TG 425, adopted October 3, 2008). Blood samples were hematologically and biochemically analyzed and multiple tissue sections from each organ were examined using light microscopy. Cytotoxicity of various A. rugosum extracts was also determined against MCF-7 and A-549 cell lines. Our results showed that oral administration of a single dose of mycelial powder (2000 mg/kg) had no adverse effect on the growth rate or hematological and clinical biochemical parameters. Histological studies showed that the treatments did not induce any pathological changes in the organs of the tested animals. All the treated rats survived beyond the 14-day observation period. Methanol and cold and hot water extracts of the freeze-dried mycelial culture of A. rugosum exhibited no or little cytotoxic effect against the MCF-7 and A-549 cell lines.
This study investigated antioxidant and anti-inflammatory properties, and the direct cytotoxic effect of Lignosus rhinocerotis fractions, especially the polysaccharide fraction, on nasopharyngeal carcinoma cells. L. rhinocerotis crude extract was obtained through hot water extraction. The precipitate saturated with 30% ammonium sulfate was purified with ion-exchanged chromatography. Gel permeation chromatography multiangle laser light scattering analysis equipped with light scattering and UV signals revealed two district groups of polymers. A total of four peaks were observed in the total carbohydrate test. Fraction C, which was the second region of the second peak eluted with 0.3 M NaOH, showed the highest integrated molecular weight, whereas fraction E had the lowest integrated molecular weight of 19,790 Da. Fraction A contained the highest β-D-glucan content. Enzymatic analysis showed that most of the polysaccharide fractions contained β-1-3 and β-1-6 skeletal backbones. The peak eluted with 0.6 M NaOH was separated in fraction D (flask 89-92) and fraction E (93-96). The results showed that fraction E expressed higher antioxidant activities than fraction D whereas fraction D expressed higher chelating activity than fraction E. The extract saturated with 30% ammonium sulfate exhibited higher reducing power than the extract saturated with 100% ammonium sulfate. Fractions D and E significantly inhibited the secretion of tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. There was no apparent difference in the viability of cells exposed or unexposed to L. rhinocerotis fractions.
Traditional use of the tiger milk medicinal mushroom, Lignosus rhinocerus, to treat various illnesses has been recorded for > 4 centuries. Successful cultivation of L. rhinocerus using proprietary solid-state fermentation (SSF) technology by LiGNO Biotech has enabled large-scale production of L. rhinocerus sclerotia (termed L. rhinocerus TM02) and further investigations into its medicinal properties. Pharmacological activities of L. rhinocerus TM02, including its antioxidant, anti-inflammatory, anticancer, and immunomodulatory effects and the bioactive components responsible, have been validated by various scientific studies. In this study, we assessed the consistency of the bioactive components in 11 batches of L. rhinocerus TM02 produced over a 9-year period. The different batches of L. rhinocerus TM02 consisted of stable protein, polysaccharide, and glycoprotein contents, and all tested samples were comparable to the wild type. L. rhinocerus TM02 had greater protein, carbohydrate, and glycoprotein contents, which were mostly bioactive compared to another cultivar from a different cultivation technology (TM-UN). Together with previous scientific validations, L. rhinocerus TM02 produced using SSF cultivation is of optimal quality with high consistent bioactive contents, which can be an appropriate indicator for quality validation of the much sought-after medicinal mushroom, L. rhinocerus.
The growth and lectin production of Ganoderma applanatum, a white rot fungus, was optimized in broth cultures. The fungus was found to have a higher growth rate and higher lectin activity when grown in a medium adjusted to pH 6.5 at 26°C under stationary conditions. Expression of lectin activity started in 5-day-old mycelial culture; maximum activity was expressed after the 15th day of incubation. Among the various carbon and nitrogen sources tested, the carbon source sucrose and the nitrogen source yeast extract support maximum growth and lectin production. Lectin from G. applanatum was purified by ammonium sulfate precipitation and ion exchange chromatography. The purified fraction revealed a single band with a molecular weight of 35.0 kDa. Moreover, carbohydrates such as mannitol, glucose, sucrose, maltose, mannose, galactose, sorbose, and fructose were found to inhibit the hemagglutinating activity of the lectin. The purified lectins from G. applanatum contain cytotoxic and proapoptotic activities against HT-29 colon adenocarcinoma cells.
Pleurotus eryngii (king oyster mushroom) is a renowned culinary mushroom with various medicinal properties that may be beneficial for health maintenance and disease prevention. However, its effect on the nervous system remains elusive. In this study, hot water (PE-HWA) and ethanol (PE-ETH) extracts of P. eryngii were investigated and compared for their neuroprotective, anti-inflammatory, and neurite outgrowth activities in vitro. Based on the results, both extracts up to 400 μg/mL were nontoxic to PC12 cells and BV2 microglia (p > 0.05). Treatment with 250 μM hydrogen peroxide (H2O2) markedly (p < 0.0001) reduced the PC12 cell viability to 67.74 ± 6.47%. Coincubation with 200 μg/mL and 400 μg/mL of PE-ETH dose-dependently increased the cell viability to 85.34 ± 1.91% (p < 0.001) and 98.37 ± 6.42% (p < 0.0001) respectively, while PE-HWA showed no activity. Nitric oxide (NO) released by BV2 microglia was notably (p < 0.0001) increased by 1 μg/mL lipopolysaccharides (LPS) from 7.46 ± 0.73 μM to 80.00 ± 3.78 μM indicating an inflammatory reaction. However, coincubation with 200 and 400 μg/mL of PE-ETH significantly (p < 0.0001) reduced the NO level to 58.57 ± 6.19 μM and 52.86 ± 3.43 μM respectively, while PE-HWA was noneffective. PE-ETH and PE-HWA at 40 μg/mL significantly increased the neurite-bearing cells from 4.70 ± 3.36% to 13.12 ± 2.82% (p < 0.01) and 20.93 ± 5.37% (p < 0.0001) respectively. Pleurotus eryngii, particularly the ethanol extract (PE-ETH) and its potentially bioactive compounds, could be explored as a neurohealth promoting agent, due to its collective neuroprotective, anti-inflammatory, and neurite outgrowth activities.
Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.
In general, Cordyceps sinensis is much more popular than C. militaris, though both species contain quite similar bioactive ingredients and exhibit medicinal activities. Many bioactive ingredients have been isolated from C. militaris, such as adenosine, cordycepin, D-mannitol, and exopolysaccharides. C. militaris is claimed to have extensive pharmacological properties, such as: anti-inflammatory; anti-fatigue; anti-bacterial; anti-diabetic; improve lung, liver, and kidney functions; to be beneficial for treating cancer as well as male and female sexual dysfunctions. C. militaris is fast gaining momentum for its so-called health benefits, and it is often used as a substitute for C. sinensis. In view of the growing popularity of C. militaris, nowadays C. militaris cultivation for stroma is also done. There is a great diversity of compounds from different strains of Cordyceps and different artificially cultivated products. This study is to determine the optimum culture parameters integrated with substrate of choice to bring the indoor-cultivated C. militaris to a higher and more consistent level of quality. To achieve the above objective, the resultant products after growth were analyzed for adenosine, cordycepin, and D-mannitol using the high-performance liquid chromatography method. The optimum culture condition to produce a high level of adenosine is by using millet as solid substrate. It must be cultivated in the dark for the first 7 days and harvested on day 40. The optimum culture condition to produce a high level of cordycepin is by using soybean as solid substrate. It must be cultivated in the dark for the first 14 days and harvested on day 50. While a high level of D-mannitol is achieved with millet as the solid substrate. It must be kept in the dark for the first 7 days and harvested on day 50. The adenosine level decreased and cordycepin increased from day 40 of culture to day 50 generally.
A central composite design of response surface methodology (RSM) was employed to optimize the extraction time (X1: 266.4-393.6 min) and temperature (X2: 42.9-57.1°C) of Pleurotus ostreatus aqueous extract with high antioxidant activities, namely DPPH radical-scavenging activity, ABTS radical cation inhibition, and ferric reducing/antioxidant power, as well as total phenolic content (TPC). Results showed that the data were adequately fitted into four second-order polynomial models developed by RSM. The extraction time and temperature were found to have significant quadratic effects on antioxidant activities and TPC. The optimal extraction time and temperature were 282.3 min and 42.9°C (DPPH), 393.6 min and 42.9°C (ABTS), 340.4 min and 49.8°C (FRAP), and 347.6 min, 49.7°C (TPC), with corresponding yields of 53.32%, 73.20%, 37.14 mM Fe2+ equivalents/100 g, and 826.33 mg gallic acid equivalents/100 g, respectively. These experimental data were close to their predicted values. The establishment of such a model provides a good experimental basis for employing RSM to optimize the extraction time and temperature for high antioxidant activities from P. ostreatus.
Neurodegeneration is one of the most common manifestations in an aging population. The occurrence of oxidative stress and neuroinflammation are the main contributors to the phenomenon. Neurologic conditions such as Alzheimer's disease (AD) and Parkinson's disease (PD) are challenging to treat due to their irreversible manner as well as the lack of effective treatment. Grifola frondosa (Dicks.: Fr.) S.F. Gray, or maitake mushroom, is believed to be a potential choice as a therapeutic agent for neurodegenerative diseases. G. frondosa is known to be a functional food that has a wide variety of medicinal purposes. Thus, this review emphasizes the neuroprotective effects and the chemical composition of G. frondosa. Various studies have described that G. frondosa can protect and proliferate neuronal cells through neurogenesis, antioxidative, anti-inflammatory, and anti-β-amyloid activities. The mechanism of action behind these therapeutic findings in various in vitro and in vivo models has also been intensively studied. In this mini review, we also summarized the chemical composition of G. frondosa to provide a better understanding of the presence of nutritional compounds in G. frondosa.
Cordyceps militaris is known for its curative properties. The present study was undertaken to evaluate the reduction of nitric oxide production by BV2 cells by the bioactive fraction of stroma powder of C. militaris, and to deduce the potential chemical components and pathways that may be responsible. The CE2 fraction from ethyl acetate extract did not exert any cytotoxic effects toward the BV2 cells at concentrations 0.1 to 100 μg/mL. The CE2 fraction also showed a significant (p < 0.05) reduction in nitric oxide production at 1-100 μg/mL. At 10 μg/mL, the CE2 fraction attenuated 85% of the NO production in BV2 cells. Further, the CE2 fraction (10 μg/mL) downregulated inflammatory genes, iNOS and COX-2, and upregulated anti-inflammatory genes, HO-1 and NQO-1. The CE2 fraction reduced NO production via activation of NRF2 and NF-κB transcriptions. The chemical constituents of the bioactive CE2 fraction were identified via GCMS. Eleven lipid components were identified including fatty acids, fatty acid esters, and sterols.
The aim of this study was to determine the antiulcer activity of Lignosus rhinocerotis in rats. A total of 48 Sprague-Dawley rats were used in ethanol-induced, aspirin-induced, and water immersion-restraint stress-induced ulcer models. Rats were equally divided into 4 groups for each model and orally administered 5 mL/kg distilled water, 20 mg/kg omeprazole, as well as 250 and 500 mg/kg of L. rhinocerotis powder. L. rhinocerotis powder at both 250 and 500 mg/kg doses demonstrated significant (P < 0.05) protection against gastric ulceration in all the induced ulcer models. Histological studies revealed severe damage and hemorrhage of gastric mucosa in the negative control group for all ulcer-induced models. The study suggests that L. rhinocerotis powder possesses dose-dependent antiulcer activity in the gastric mucosa, as ascertained grossly and histologically, compared with the negative control groups.