The edible mushroom Pleurotus giganteus was tested for its effect on adipocyte differentiation and glucose uptake activity in 3T3-L1 cells. The basidiocarps of P. giganteus were soaked in methanol to obtain a crude methanol extract and then fractionated to obtain an ethyl acetate extract. In this study, cell proliferation was measured using an MTT assay, lipid accumulation using an Oil Red O assay, and glucose uptake using a fluorescence glucose uptake assay. Gene expression was measured via real-time polymerase chain reaction analysis with TaqMan primer. Ethyl acetate extract significantly enhanced adipogenic differentiation and glucose uptake in 3T3-L1 adipocytes via the expression of sterol regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and phos-phatidylinositol 3-kinase/Akt. Glucose uptake was facilitated by the highly expressed glucose transporters Glut1 and Glut4. Taken together, these results suggest that P. giganteus ethyl acetate extract has an insulin-sensitizing effect on adipocytes and has potential as an adjuvant for the management of type 2 diabetes.
Ophiocordyceps sinensis (=Cordyceps sinensis) has been known for its various medicinal properties, in particular immunomodulatory activities associated with its polysaccharides. In this study, the fruiting body of O. sinensis cultivar OCS02® was investigated for its chemical composition and monosaccharide profile. Cold water extract (CWE) obtained from this fruiting body was fractionated by molecular weight (MW) into high (HMW), medium (MMW), and low (LMW) fractions. Polysaccharides in the extract and fractions were identified as heteroglycans containing mostly glucose and mannose with small amounts of galactose, fucose, arabinose, and xylose. The immunomodulatory potential of these heteroglycans was evaluated by induction of cytokine/chemokine secretion using murine macrophage RAW 264.7. All treatments showed significant modulation of IL-6, IL-9, MIP-2, and TIMP-1, especially for CWE, HMW, and MMW, which might be due to their high ratios of glucose and the presence of protein. Further investigation on the structure-function relationship of these fruiting body polysaccharide fractions is needed to delineate the underlying mechanism of their immunomodulatory effect both in vitro and in vivo.
Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common liver diseases worldwide. Lifestyle modifications through the diet are the mainstay of treatment. Auricularia nigricans is a popular edible mushroom known to possess medicinal properties. Gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry analysis indicated that linoleic acid ethyl ester, butyl 9,12-octadecadienoate, 9,12-octadecadienoic acid, ergosta-5,7,22-trien-3-ol, 2(3,4-dihydroxyphenyl)-7-hydroxy-5-benzene propanoic acid, and 3,30-di-0-methyl ellagic acid were present in the A. nigricans ethyl acetate (EA) fraction. The cytotoxicity assay showed that the EA fraction was noncytotoxic to HepG2 cells at concentrations < 100 μg/mL. In the antihepatic steatosis assay, 50 μg/mL of EA fraction caused a decline in absorbance to 0.20 ± 0.02 compared to palmitic acid (PA)-induced cells (0.24 ± 0.02). Furthermore, cells treated with 50 μg/mL and 25 μg/mL of EA fraction contributed an approximately 1.12-fold and 1.08-fold decrease in lipid accumulation compared to PA-induced cells. Coincubation with PA and 25 μg/mL of EA fraction decreased levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 to 140.48 ± 8.12, 91.16 ± 2.40, 184.00 ± 22.68, and 935.88 ± 39.36 pg/mL compared to PA-induced cells. The presence of the EA fraction also suppressed the stress-activated protein kinase/Jun amino-terminal kinase, p-38 mitogen-activated protein kinase, nuclear factor-κB, and signal transducer and activator of transcription 3 signaling pathways. In conclusion, these findings suggest that the A. nigricans EA fraction demonstrates antisteatotic effects involving antioxidant capacity, hypolipidemic effects, and anti-inflammatory capacity in the PA-induced NAFLD pathological cell model.
Rigorous research has been carried out regarding the cultivation of Ganoderma lucidum using different agricultural residues. Nevertheless, large-scale cultivation and the separation of active compounds of G. lucidum are still challenges for local farmers. The objective of this study was to evaluate the use of oil palm waste fibers such as empty fruit bunch fibers and mesocarp fibers as effective substrates for the growth of G. lucidum mycelia to study the possibility of solid-state cultivation and to determine the optimum conditions necessary for the growth of mycelia of this mushroom on these waste fibers. Various parameters such as temperature, pH, humidity, and carbon and nitrogen compositions required for the optimum growth of mycelia have been determined. Oil palm fibers are a vivid source of lignocellulose, and their availability in Malaysia is high compared to that of sawdust. G. lucidum is a wood-rotting fungi that can easily decay and utilize this lignocellulose biomass, a major agricultural waste in Malaysia.
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.
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.
Hypercholesterolemia has been implicated as one of the pathomechanistic factors of Alzheimer's disease (AD), the most common neurodegenerative disorder affecting memory and learning abilities. In the present study, ameliorative effect of hot water extract (HWE) of mushroom Ganoderma lucidum to the memory and learning related behavioral performance of hypercholesterolemic and AD rats was investigated using Morris water maze (MWM). Male Wistar rats were randomly grouped into control, extract fed control, hypercholesterolemic, extract fed hypercholesterolemic, AD, and extract fed AD groups, each group containing 8 animals. Hypercholesterolemia was induced in rats by adding 1% cholesterol and 1% cholic acid with the basal diet of the respective group. Alzheimer's disease model rats were prepared through infusion of amyloid β(1-42) to the right ventricle. Memory and learning related performance of all the rats was tested for 6 consecutive days that included time taken to reach the submerged platform (sec) and distance traveled (m). G. lucidum HWE fed rats took less time and traveled less distance to find the submerged platform, which indicates the spatial learning and memory related behavioral amelioration of the extract fed rats compared with their non-fed counterparts. Thus, usage of G. lucidum seems promising in withstanding hypercholesterolemia-induced Alzheimer's disease pathogenesis.
Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting memory and learning of aged people. Hypercholesterolemia had been implicated as one of the stark hallmarks of AD. Recent AD control guidelines have suggested lifestyle modification to slow down the progression of AD. In this regard, medicinal mushroom Ganoderma lucidum seems apt. In the present study, hot water extract of G. lucidum (200 mg/kg body weight) was fed to the hypercholesterolemic and AD model rats for 8 weeks. Nonspatial memory and learning abilities of the model animals was assessed using novel object recognition (NOR) test, rotarod test, and locomotor/open-field test. Then, the animals were sacrificed and transmission electron micrograph (TEM) view of the hippocampal neurons was assessed. In all the nonspatial memory and learning tests, the G. lucidum HWE fed rats performed better indicating improved memory and learning abilities. TEM view showed regular arrangement of the neurons in the G. lucidum HWE fed rats compared with those of the deranged arrangement of the AD rats. G. lucidum might have aided in restoring the memory and learning abilities of the AD model animals through maintaining neuronal structure and function. Thus, G. lucidum could be suggested as a medicotherapeutic agent against AD.
Neurodegenerative disease is defined as a deterioration of the nervous system in the intellectual and cognitive capabilities. Statistics show that more than 80-90 million individuals age 65 and above in 2050 may be affected by neurodegenerative conditions like Alzheimer's and Parkinson's disease. Studies have shown that out of 2000 different types of edible and/or medicinal mushrooms, only a few countable mushrooms have been selected until now for neurohealth activity. Hericium erinaceus is one of the well-established medicinal mushrooms for neuronal health. It has been documented for its regenerative capability in peripheral nerve. Another mushroom used as traditional medicine is Lignosus rhinocerotis, which has been used for various illnesses. It has been documented for its neurite outgrowth potential in PC12 cells. Based on the regenerative capabilities of both the mushrooms, priority was given to select them for our study. The aim of this study was to investigate the potential of H. erinaceus and L. rhinocerotis to stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina from chick embryo when compared to brain derived neurotrophic factor (BDNF). Neurite outgrowth activity was confirmed by the immu-nofluorescence method in all tissue samples. Treatment with different concentrations of extracts resulted in neuronal differentiation and neuronal elongation. H. erinaceus extract at 50 µg/mL triggered neurite outgrowth at 20.47%, 22.47%, and 21.70% in brain, spinal cord, and retinal cells. L. rhinocerotis sclerotium extract at 50 µg/mL induced maximum neurite outgrowth of 20.77% and 24.73% in brain and spinal cord, whereas 20.77% of neurite outgrowth was observed in retinal cells at 25 µg/mL, respectively.
Dyslipidemia is the key precursor of atherosclerotic cardiovascular disease. The aim of this study was to investigate the lipid-modifying potential of organic solvent-partitioned extracts from fruiting bodies of Amauroderma rugosum in vitro using oleate-induced human hepatocellular liver carcinoma (HepG2) cells. Our results demonstrated that oleate-induced HepG2 cells treated with ethyl acetate (EA) extract greatly decreased intracellular and secreted total triglyceride (TG) and total cholesterol (TC) compared with other extracts. Further investigation of cellular expression of selected apolipoproteins also revealed that oleate-induced HepG2 cells treated with the EA extract best attenuated the apolipoprotein (Apo) profile by downregulating ApoB-100 and ApoE while upregulating ApoA1. Because both ApoB-100 and ApoE are key components of low-density lipoprotein (LDL) and very LDL (VLDL), which are recognized as "bad cholesterol," this result indicates that treatment with the EA extract inhibited LDL and VLDL production in oleate-induced HepG2 cells. On the other hand, increasing ApoA1 evidence shows antiatherogenic benefits to increasing ApoA1, the key component of high-density lipoprotein (HDL), particularly in relation to its role in promoting reverse cholesterol transport and preventing LDL oxidation; this indicates that the EA extract upregulated the production of HDL ("good cholesterol"). Hence, the EA extract is a good source of lipid-ameliorating agents in the management of dyslipidemia.
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.
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.
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.
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.
Neuritin is important in neuritogenesis, neurite arborization, and neurite extension. Lignosus rhinocerotis sclerotia extracts and nerve growth factor (NGF) have been well documented to possess positive neurite stimulatory effects. However, the correlation of neuritin expression with neurite outgrowth of L. rhinocerotis and NGF cotreatment of PC12 cells remains unknown. Thus, the present study investigated neuritin expression in PC12 cells treated with 5 ng/mL of NGF and L. rhinocerotis extracts (20-1280 μg/mL) concurrently for 48 h. The neurite outgrowth score was quantitated, and total protein was harvested for enzyme-linked immunosorbent assay. There was a significant difference (P = 0.051) in neuritin protein abundance in 640 μg/mL of L. rhinocerotis aqueous cotreatment with 5 ng/mL of NGF-treated cells (5 ± 0.39 ng/mL) and 50 ng/mL of NGF-treated PC12 cells (5 ± 0.48 ng/mL) compared to untreated cells (1.9 ± 0.65 ng/ mL), with an average neurite length of 98 ± 3.66, 106 ± 3.00, and 73 ± 4.79 μm, respectively. Expression of microtubule element β3 tubulin was increased in PC12 cells treated with 50 ng/mL of NGF (3.5 ± 0.21-fold) and also cells cotreated with 640 μg/mL of extract and 5 ng/mL of NGF (4.9 ± 0.29-fold) compared to untreated cells. Upregulation of β3 tubulin expression in this study confirmed the elongation of PC12 cell processes. Correlation analysis showed that neuritin protein abundance is positively proportional to the average neurite length in PC12 cells cotreated with L. rhinocerotis extract and 5 ng/mL of NGF. This study highlights that neuritin modulation is involved in neurite outgrowth induced by L. rhinocerotis treatment. To our knowledge, this is the first report to show that tiger milk mushroom extracts induce neuritin expression.
We present a model case study of the activity of aqueous extract of Hericium erinaceus fresh fruit bodies in promoting functional recovery following crush injury to the peroneal nerve in adult female Sprague-Dawley rats. The aim was to explore the possible use of this mushroom in nerve repair. The activities of aqueous extract were compared to activities exhibited by mecobalamin (vitamin B12), which has been widely used in the treatment of peripheral nerve disorders. Analysis of walking track indicated that return of hind limb function and normal toe spreading occurred earlier in treated groups than in the negative control (non-treated) group. Regeneration of axons and reinnervation of motor endplates/neuromuscular junction in extensor digitorum longus muscle of rats in treated groups developed better than in the negative control group. Further, immunofluorescence studies also showed that dorsal root ganglia neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt and MAPK signaling pathways as well as c-Jun and c-Fos genes compared to the negative control group. Akt cascade plays a major role in mediating neurotrophin-promoted cell survival, while MAPK cascade is involved in mediating neurite outgrowth. Immediate early gene expression was also involved in the cascade of events leading to regeneration. Local axonal protein synthetic machinery was also enhanced in the distal segments of crushed nerves in treated groups. Therefore, daily oral administration of H. erinaceus could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.
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.
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.
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.
The oxidative stability of sunflower oil supplemented with medicinal split gill mushroom, Schizophyllum commune's crude extract (CE), the formic acid (FA) fraction and semipurified subfractions (SF) II and IV were tested, compared to BHA and alpha-tocopherol, by measuring their peroxide value, iodine value, p-anisidine value, thiobarbituric acid-reactive substances, and free fatty acid content. Their total phenolic content (TPC), 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging, and ferric reducing/antioxidant power (FRAP) were also evaluated. FA and CE exhibited highest DPPH* scavenging, while FA and SFIV showed the highest FRAP; TPC was found to be highest in CE, FA, and SFIV. BHA and alpha-tocopherol are more protective in stabilizing the sunflower oil; SFII and SFIV had short-term protective effect in secondary oxidation for 1 year, while CE and FA retarded secondary oxidation and extended the shelf life 1 1/2 years and 2 years, respectively. HPLC-DAD analysis found (+)-catechin in Sch. commune's extracts. Sch. commune's extracts did not show similar retardation of lipid oxidation in sunflower oil as compared to alpha-tocopherol and BHA at the 200 ppm level. However, the higher concentration of Sch. commune's extract that provided the protective effect in stabilizing sunflower oil can be further studied.