Displaying publications 1 - 20 of 29 in total

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  1. Ali SM, Raman J, Lakshmanan H, Ling TC, Phan CW, Tan YS, et al.
    Int J Med Mushrooms, 2018;20(11):1021-1030.
    PMID: 30806227 DOI: 10.1615/IntJMedMushrooms.2018028307
    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.
  2. Apparoo Y, Phan CW, Kuppusamy UR, Sabaratnam V
    Exp Gerontol, 2022 Dec;170:111982.
    PMID: 36244584 DOI: 10.1016/j.exger.2022.111982
    Healthy ageing is a crucial process that needs to be highlighted as it affects the quality of lifespan. An increase in oxidative stress along with ageing is the major factor related to the age-associated diseases, especially neurodegenerative disorders. An antioxidant-rich diet has been proven to play a significant role in the ageing process. Targeting ageing mechanisms could be a worthwhile approach to improving health standards. Ergothioneine (EGT), a hydrophilic compound with specific transporter known as OCTN1, has been shown to exert anti-ageing properties. In addition to its antioxidant effect, EGT has been reported to have anti-senescence, anti-inflammatory and anti-neurodegenerative properties. This review aims to define the pivotal role of EGT in major signalling pathways in ageing such as insulin/insulin-like growth factor (IGF) signalling (IIS), sirtuin 6 (SIRT6) and mammalian target of rapamycin complex (mTOR) pathways. The review further discusses evidence of EGT on neurodegeneration in its therapeutic context in various model organisms, providing new insights into improving health. In conclusion, an ergothioneine-rich diet may be beneficial in preventing age-related diseases, resulting in a healthy ageing population.
  3. Chan XH, Sabaratnam V, Abdullah N, Phan CW
    Int J Med Mushrooms, 2020;22(6):521-534.
    PMID: 32865894 DOI: 10.1615/IntJMedMushrooms.2020035031
    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.
  4. Cheng PG, Phan CW, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR
    PMID: 24348715 DOI: 10.1155/2013/671252
    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.
  5. Dhakal S, Kushairi N, Phan CW, Adhikari B, Sabaratnam V, Macreadie I
    Int J Mol Sci, 2019 Oct 14;20(20).
    PMID: 31615073 DOI: 10.3390/ijms20205090
    Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.
  6. Ellan K, Thayan R, Phan CW, Sabaratnam V
    Trop Biomed, 2019 Dec 01;36(4):1087-1098.
    PMID: 33597478
    Pathogenesis of dengue fever has been associated with the activation of the cytokine cascade that triggered inflammatory responses. The inflammatory reactions in dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) are the main cause of haemorrhagic manifestations, coagulation disorders, vascular permeability, hypotension and shock which could exacerbate the condition of the disease. In an earlier study, extracts belonging to Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune and Ganoderma lucidium mushrooms were screened for antidengue virus activities. We found that hot aqueous extract (HAE) and aqueous soluble separated from ethanol extract (ASE) exhibited their potential to reduce dengue viral load which were observed in plaque reduction assay and real-time RT-PCR. In continuation of our previous findings, this study was initiated to further investigate the other aspect; the anti-inflammatory activities of HAE and ASE of L. rhinocerotis, P. giganteus, H. erinaceus, S. commune and G. lucidium on human monocytes infected with dengue virus-2 (DENV-2) New guinea C strain. Human monocytes infected with DENV-2 were treated with mushroom extracts for 48 hours. The cytokine profile coincides with dengue infection, i.e. IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-10 were measured by BD OptEIATM Elisa Kit. The expression of these cytokines was significantly elevated in untreated infected cells two days after infection. However, after treated with mushroom extracts prominent anti-inflammatory effect were detected towards IFN-γ, IL-10, TNF-α, IL-6, and IL-1β. The most significant anti-inflammatory effects were detected in HAE of G. lucidium, S. commune, P. giganteus and ASE of L. rhinocerotis and the effects were comparable with dexamethasone, the reference inhibitor. These results demonstrated that mushroom HAE or ASE could successfully have suppressed cytokine production in dengue-infected monocytes and has a great potential to develop an antiinflammatory agent from mushroom extract for the treatment of dengue infection.
  7. Kushairi N, Phan CW, Sabaratnam V, Vidyadaran S, Naidu M, David P
    Int J Med Mushrooms, 2020;22(12):1171-1181.
    PMID: 33463934 DOI: 10.1615/IntJMedMushrooms.2020036938
    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.
  8. Naguib AM, Apparoo Y, Xiong C, Phan CW
    Int J Med Mushrooms, 2023;25(2):11-22.
    PMID: 36749053 DOI: 10.1615/IntJMedMushrooms.2022046849
    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.
  9. Nallathamby N, Phan CW, Sova M, Saso L, Sabaratnam V
    Med Chem, 2021;17(6):623-629.
    PMID: 31849289 DOI: 10.2174/1573406416666191218095635
    BACKGROUND: Microglia are associated with neuroinflammation, which play a key role in the pathogenesis of neurodegenerative diseases. It has been reported that some quinazolines and quinazolinones possess anti-inflammatory properties. However, the pharmacological properties of certain quinazoline derivatives are still unknown.

    OBJECTIVE: The antioxidant, cytotoxic, and protective effects of a series of synthesized 2- trifluoromethylquinazolines (2, 4, and 5) and quinazolinones (6-8) in lipopolysaccharide (LPS)- murine microglia (BV2) and hydrogen peroxide (H2O2)-mouse neuroblastoma-2a (N2a) cells were investigated.

    METHOD: The antioxidant activity of synthesized compounds was evaluated with ABTS and DPPH assays. The cytotoxic activities were determined by MTS assay in BV2 and N2a cells. The production of nitric oxide (NO) in LPS-induced BV2 microglia cells was quantified.

    RESULTS: The highest ABTS and DPPH scavenging activities were observed for compound 8 with 87.7% of ABTS scavenge percentage and 54.2% DPPH inhibition. All compounds were noncytotoxic in BV2 and N2a cells at 5 and 50 μg/mL. The compounds which showed the highest protective effects in LPS-induced BV2 and H2O2-induced N2a cells were 5 and 7. All tested compounds, except 4, also reduced NO production at concentrations of 50 μg/mL. The quinazolinone series 6-8 exhibited the highest percentage of NO reduction, ranging from 38 to 60%. Compounds 5 and 8 possess balanced antioxidant and protective properties against LPS- and H2O2-induced cell death, thus showing great potential to be developed into anti-inflammatory and neuroprotective agents.

    CONCLUSION: Compounds 5 and 7 were able to protect the BV2 and N2a cells against LPS and H2O2 toxicity, respectively, at a low concentration (5 μg/mL). Compounds 6-8 showed potent reduction of NO production in BV2 cells.

  10. Nallathamby N, Malek SNA, Vidyadaran S, Phan CW, Sabaratnam V
    Int J Med Mushrooms, 2020;22(12):1215-1223.
    PMID: 33463938 DOI: 10.1615/IntJMedMushrooms.2020037001
    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.
  11. Nallathamby N, Phan CW, Seow SL, Baskaran A, Lakshmanan H, Abd Malek SN, et al.
    Front Pharmacol, 2017;8:998.
    PMID: 29379443 DOI: 10.3389/fphar.2017.00998
    Edible and medicinal mushrooms are regularly used in natural medicines and home remedies since antiquity for ailments like fever, inflammation, and respiratory disorders. Lignosus rhinocerotis (Cooke) Ryvarden is a polypore found in Malaysia and other regions in South East Asia. It can be located on a spot where a tigress drips milk while feeding, hence the name "tiger's milk mushroom." The sclerotium of L. rhinocerotis is highly sought after by the native communities in Malaysia to stave off hunger, relieve cough and asthma, and provide stamina. The genomic features of L. rhinocerotis have been described. The pharmacological and toxicity effects, if any, of L. rhinocerotis sclerotium have been scientifically verified in recent years. In this review, the validated investigations including the cognitive function, neuroprotection, immune modulation, anti-asthmatic, anti-coagulation, anti-inflammatory, anti-microbial/ anti-viral, anti-obesity, anti-cancer/ anti-tumor, and antioxidant properties are highlighted. These findings suggest that L. rhinocerotis can be considered as an alternative and natural medicine in the management of non-communicable diseases. However, there is a paucity of validation studies including human clinical trials of the mycochemicals of L. rhinocerotis.
  12. Phan CW, Lee GS, Hong SL, Wong YT, Brkljača R, Urban S, et al.
    Food Funct, 2014 Dec;5(12):3160-9.
    PMID: 25288148 DOI: 10.1039/c4fo00452c
    Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.
  13. Phan CW, David P, Tan YS, Naidu M, Wong KH, Kuppusamy UR, et al.
    ScientificWorldJournal, 2014;2014:378651.
    PMID: 25121118 DOI: 10.1155/2014/378651
    Two strains of Pleurotus giganteus (commercial and wild) were tested for their ability to induce neurite outgrowth in rat pheochromocytoma (PC12) and mouse neuroblastoma-2a (N2a) cells. Treatment with the mushroom extracts resulted in neuronal differentiation and neuronal elongation, but not nerve growth factor (NGF) production. Linoleic acid (4.5-5.0%, w/w) which is a major fatty acid present in the ethanol extract promoted NGF biosynthesis when augmented with low concentration of NGF (5 ng/mL). The two strains of mushroom were found to be high in protein (154-192 g kg(-1)), total polysaccharides, phenolics, and flavonoids as well as vitamins B1, B2, and B3. The total phenolics present in the mushroom extracts were positively correlated to the antioxidant activity (free radical scavenging, ferric reducing power, and lipid peroxidation inhibition). To conclude, P. giganteus could potentially be used in well-balanced diet and as a source of dietary antioxidant to promote neuronal health.
  14. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V
    Crit Rev Biotechnol, 2015;35(3):355-68.
    PMID: 24654802 DOI: 10.3109/07388551.2014.887649
    Mushrooms have long been used not only as food but also for the treatment of various ailments. Although at its infancy, accumulated evidence suggested that culinary-medicinal mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Therefore, efforts have been devoted to a search for more mushroom species that may improve memory and cognition functions. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Sarcodon spp., Antrodia camphorata, Pleurotus giganteus, Lignosus rhinocerotis, Grifola frondosa, and many more. Here, we review over 20 different brain-improving culinary-medicinal mushrooms and at least 80 different bioactive secondary metabolites isolated from them. The mushrooms (either extracts from basidiocarps/mycelia or isolated compounds) reduced beta amyloid-induced neurotoxicity and had anti-acetylcholinesterase, neurite outgrowth stimulation, nerve growth factor (NGF) synthesis, neuroprotective, antioxidant, and anti-(neuro)inflammatory effects. The in vitro and in vivo studies on the molecular mechanisms responsible for the bioactive effects of mushrooms are also discussed. Mushrooms can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro evidence and clinical trials with humans are needed.
  15. Phan CW, Lee GS, Macreadie IG, Malek SN, Pamela D, Sabaratnam V
    Nat Prod Commun, 2013 Dec;8(12):1763-5.
    PMID: 24555294
    Different solvent extracts of Pleurotus giganteus fruiting bodies were tested for antifungal activities against Candida species responsible for human infections. The lipids extracted from the ethyl acetate fraction significantly inhibited the growth of all the Candida species tested. Analysis by GC/MS revealed lipid components such as fatty acids, fatty acid methyl esters, ergosterol, and ergosterol derivatives. The sample with high amounts of fatty acid methyl esters was the most effective antifungal agent. The samples were not cytotoxic to a mammalian cell line, mouse embryonic fibroblasts BALB/c 3T3 clone A31. To our knowledge, this is the first report of antifungal activity of the lipid components of Pleurotus giganteus against Candida species.
  16. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V
    PMID: 24119256 DOI: 10.1186/1472-6882-13-261
    Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity.
  17. Phan CW, Wong WL, David P, Naidu M, Sabaratnam V
    PMID: 22812497 DOI: 10.1186/1472-6882-12-102
    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal.
  18. Phan CW, Sabaratnam V, Bovicelli P, Righi G, Saso L
    Biofactors, 2016 Nov 12;42(6):591-599.
    PMID: 27193378 DOI: 10.1002/biof.1296
    Negletein has been shown to have therapeutic potential for inflammation-associated diseases, but its effect on neurite outgrowth is still unknown. The present study showed that negletein alone did not trigger PC12 cells to differentiate and extend neurites. When compared with the cells in the untreated control, a significant (P 
  19. Phan CW, Sabaratnam V
    Appl Microbiol Biotechnol, 2012 Nov;96(4):863-73.
    PMID: 23053096 DOI: 10.1007/s00253-012-4446-9
    Mushroom industries generate a virtually in-exhaustible supply of a co-product called spent mushroom substrate (SMS). This is the unutilised substrate and the mushroom mycelium left after harvesting of mushrooms. As the mushroom industry is steadily growing, the volume of SMS generated annually is increasing. In recent years, the mushroom industry has faced challenges in storing and disposing the SMS. The obvious solution is to explore new applications of SMS. There has been considerable discussion recently about the potentials of using SMS for production of value-added products. One of them is production of lignocellulosic enzymes such as laccase, xylanase, lignin peroxidase, cellulase and hemicellulase. This paper reviews scientific research and practical applications of SMS as a readily available and cheap source of enzymes for bioremediation, animal feed and energy feedstock.
  20. Phan CW, David P, Wong KH, Naidu M, Sabaratnam V
    PLoS One, 2015;10(11):e0143004.
    PMID: 26565787 DOI: 10.1371/journal.pone.0143004
    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.
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