Facts to Consider in Developing Materials That Emulate the Upper Jawbone: A Microarchitecture Study Showing Unique Characteristics at Four Different Sites.

The maxilla is generally acknowledged as being more trabecular than the mandible. Allograft currently available for use in the maxillofacial region is harvested from the hip and long bones, irrespective of their local characteristics, and grafted onto the jawbones. Other alternative are autograft or commercially available bone substitutes. Due to their inherent differences, an in-depth understanding of the bone microarchitecture is important to develop the most compatible graft for use at the maxilla. This cross-sectional study aimed to determine the microstructures of bone harvested from different sites of the maxilla, to be used for standard setting. Forty-nine specimens from seven human cadavers were harvested from the zygomatic buttress, anterior maxillary sinus wall, anterior nasal spine and anterior palate. Each bone block, measuring of 10 mm × 5 mm, was harvested using rotary instruments. Bone analysis was performed following micro-computed tomography to obtain trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and bone volume fraction (BV/TV). There were site-related differences, with BV/TV that ranged between 37.38% and 85.83%. The Tb.N was the lowest at the palate (1.12 (mm-1)) and highest at the anterior maxillary sinus wall (1.41 (mm-1)) region. The palate, however, had the highest trabecular separation value (Tb.Sp) at 0.47 mm. The TB.Th was the lowest at the anterior nasal spine (0.34 mm) but both the zygoma and anterior maxillary sinus regions shared the highest Tb.Th (0.44 mm). Except for having the lowest Th.Sp (0.35 mm), the anterior maxillary sinus wall consistently showed higher values together with the zygomatic buttress in all other parameters. Concurring with current clinical practice of harvesting autograft from the zygomatic buttress and anterior maxillary sinus wall, their bony characteristic serve as the microarchitecture standard to adopt when developing new bone graft materials for use in the maxilla.

Dental age estimation of Malaysian Indian children and adolescents: applicability of Chaillet and Demirjian's modified method using artificial neural network.

BACKGROUND: Recognising the importance of dental age (DA) estimation in forensic investigations, a variety of methods abound in the literature due to population-specific attributes. A reference eight-tooth method developed by Chaillet and Demirjian estimated the DA of children and adolescents. AIM: This study aims to investigate the applicability of Chaillet and Demirjian's method among Malaysian Indians aged 5.00-17.99 years. SUBJECTS AND METHODS: Dental panoramic tomographs of Malaysian Indians aged 5.00-17.99 years were statistically analysed using paired t-test and artificial neural networks multilayer perceptron (ANN-MLP). RESULTS: A total of 1015 dental panoramic tomographs were analysed. Paired t-test analysis against the reference dental maturity scores revealed underestimation of DA in boys of 1.68 years and girls of 2.56 years indicating inaccurate age estimation. A population-specific prediction model with a new set of dental maturity scores was established on Chaillet and Demirjian's scores using ANN-MLP. The new dental maturity scores showed accurate estimation of DA with differences between CA and DA being 12 and 25 days for boys and girls, respectively. Furthermore, a new DA prediction formula was developed using regression analysis following the establishment of new dental scores based on ANN-MLP. CONCLUSION: A novel Malaysian Indian-specific prediction model that demonstrated accurate DA estimation was established.

Discovering the Potential of Natural Antioxidants in Age-Related Macular Degeneration: A Review.

Age-related macular degeneration (AMD) is a multifactorial disease associated with anatomical changes in the inner retina. Despite tremendous advances in clinical care, there is currently no cure for AMD. This review aims to evaluate the published literature on the therapeutic roles of natural antioxidants in AMD. A literature search of PubMed, Web of Science and Google Scholar for peer-reviewed articles published between 1 January 2011 and 31 October 2021 was undertaken. A total of 82 preclinical and 18 clinical studies were eligible for inclusion in this review. We identified active compounds, carotenoids, extracts and polysaccharides, flavonoids, formulations, vitamins and whole foods with potential therapeutic roles in AMD. We evaluated the integral cellular signaling pathways including the activation of antioxidant pathways and angiogenesis pathways orchestrating their mode of action. In conclusion, we examined the therapeutic roles of natural antioxidants in AMD which warrant further study for application in clinical practice. Our current understanding is that natural antioxidants have the potential to improve or halt the progression of AMD, and tailoring therapeutics to the specific disease stages may be the key to preventing irreversible vision loss.

ß-Glucan-Rich Extract of Gray Oyster Mushroom, Pleurotus pulmonarius, Improves Object Recognition Memory and Hippocampus Morphology in Mice Fed a High-Fat Diet.

Obesity may cause behavioral alterations, while maternal obesity can contribute to metabolic disorders in subsequent generations. The effect of ß-glucan-rich Pleurotus pulmonarius (ßgPp) was investigated on mouse neurobehavior and hippocampus and its offspring's hippocampus development. Female ICR mice were fed with normal diet (ND), ND with ßgPp, high-fat diet (HFD), or HFD with ßgPp for 3 months followed by behavioral test and mating. Immunohistochemistry for the expression of neuronal nuclear protein (NeuN) and ionized calcium binding adaptor molecule-1 (Iba-1) in the hippocampus was carried out. ßgPp significantly enhanced short-term object recognition memory in HFD-fed mice. ßgPp also ameliorated the histological alterations and neuronal loss and increased Iba-1-positive microglia in the hippocampus regions of HFD-fed mice and their male offspring. These findings demonstrated that ßgPp supplementation attenuated the effects of HFD on object recognition memory and the alterations on the hippocampal regions of maternal mice and their male offspring.

Comparative Neuroprotective, Anti-Inflammatory and Neurite Outgrowth Activities of Extracts of King Oyster Mushroom, Pleurotus eryngii (Agaricomycetes).

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.

Expression Pattern of the Cancer Stem Cell Marker "Nestin" in Leukoplakia and Oral Squamous Cell Carcinoma.

OBJECTIVE: The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis. METHODS: Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expression was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters. RESULTS: Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leukoplakia, to oral squamous cell carcinoma. CONCLUSION: This study has two major findings: (1) identification of nestin as an effective indicator of neoangiogenesis, and (2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis.

Methanolic extract of Mitragyna speciosa Korth leaf inhibits ethanol seeking behaviour in mice: involvement of antidopaminergic mechanism.

In the current study, the effect of methanolic extract of Mitragyna speciosa leaf (MMS) against the rewarding and reinforcing properties of ethanol using a mouse model of conditioned place preference (CPP) and runway model of drug self-administration was studied. Subsequently, the effect of MMS on dopamine level in the nucleus accumbens (NAc) of the mouse brain was further investigated. From the data obtained, MMS (50 and 75 mg/kg, p.o.) significantly reversed the ethanol-place preference in mice, which is similar to the effect observed in the reference drugs acamprosate (300 mg/kg, p.o.) and clozapine (1 mg/kg, p.o.) treatment groups in CPP test. Likewise, the escalating doses of ethanol-conditioned mice reduced the runtime to reach goal box, infers the positive reinforcing effects of alcohol. Interestingly, MMS (50, 75 and 100 mg/kg, p.o.) significantly prolonged the runtime in ethanol-conditioned mice. Besides, MMS (50 and 75 mg/kg, p.o.) and reference drugs; acamprosate (300 mg/kg, p.o.) and clozapine (1 mg/kg, p.o.) treated mice significantly decreased the alcohol-induced elevated dopamine level in the NAc region of the brain. Overall, this study provides first evidence that MMS inhibits ethanol seeking behaviour in mice. Based on these findings, we suggest that Mitragyna speciosa may well be utilized for novel drug development to combat alcohol dependence.

Lion's Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. Suppresses H2O2-Induced Oxidative Damage and LPS-Induced Inflammation in HT22 Hippocampal Neurons and BV2 Microglia.

Oxidative stress and inflammation in neuron-glia system are key factors in the pathogenesis of neurodegenerative diseases. As synthetic drugs may cause side effects, natural products have gained recognition for the prevention or management of diseases. In this study, hot water (HE-HWA) and ethanolic (HE-ETH) extracts of the basidiocarps of Hericium erinaceus mushroom were investigated for their neuroprotective and anti-inflammatory activities against hydrogen peroxide (H2O2)-induced neurotoxicity in HT22 mouse hippocampal neurons and lipopolysaccharide (LPS)-induced BV2 microglial activation respectively. HE-ETH showed potent neuroprotective activity by significantly (p < 0.0001) increasing the viability of H2O2-treated neurons. This was accompanied by significant reduction in reactive oxygen species (ROS) (p < 0.05) and improvement of the antioxidant enzyme catalase (CAT) (p < 0.05) and glutathione (GSH) content (p < 0.01). Besides, HE-ETH significantly improved mitochondrial membrane potential (MMP) (p < 0.05) and ATP production (p < 0.0001) while reducing mitochondrial toxicity (p < 0.001), Bcl-2-associated X (Bax) gene expression (p < 0.05) and nuclear apoptosis (p < 0.0001). However, gene expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were unaffected (p > 0.05). HE-ETH also significantly (p < 0.0001) reduced nitric oxide (NO) level in LPS-treated BV2 indicating an anti-inflammatory activity in the microglia. These findings demonstrated HE-ETH maybe a potential neuroprotective and anti-inflammatory agent in neuron-glia environment.

Corrigendum to "Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)".

[This corrects the article DOI: 10.1093/ecam/neq062.].

A review on the nucleic acid constituents in mushrooms: nucleobases, nucleosides and nucleotides.

Mushrooms have become increasingly important as a reliable food source. They have also been recognized as an important source of bioactive compounds of high nutritional and medicinal values. The nucleobases, nucleosides and nucleotides found in mushrooms play important roles in the regulation of various physiological processes in the human body via the purinergic and/or pyrimidine receptors. Cordycepin, a 3'-deoxyadenosine found in Cordyceps sinensis has received much attention as it possesses many medicinal values including anticancer properties. In this review, we provide a broad overview of the distribution of purine nucleobases (adenine and guanine); pyrimidine nucleobases (cytosine, uracil, and thymine); nucleosides (uridine, guanosine, adenosine and cytidine); as well as novel nucleosides/tides in edible and nonedible mushrooms. This review also discusses the latest research focusing on the successes, challenges, and future perspectives of the analytical methods used to determine nucleic acid constituents in mushrooms. Besides, the exotic taste and flavor of edible mushrooms are attributed to several nonvolatile and water-soluble substances, including the 5'-nucleotides. Therefore, we also discuss the total flavor 5'-nucleotides: 5'-guanosine monophosphate (5'-GMP), 5'-inosine monophosphate (5'-IMP), and 5'-xanthosine monophosphate (5'-XMP) in edible mushrooms.

Tiger's Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes) Sclerotium Inhibits Nitric Oxide Production in LPS-Stimulated BV2 Microglia.

In Malaysia and China, the sclerotium of Lignosus rhinocerotis is used by local communities and traditional medicine practitioners as a general tonic and remedy to treat a variety of ailments, including inflammation-associated disorders. In this study, 10 samples from different preparations of L. rhinocerotis sclerotium, including a hot aqueous extract (HAE), an ethanol extract (EE), fractions from the HAE and EE, and crude polysaccharides, were tested for their in vitro cytotoxic and nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS)--stimulated BV2 microglia. Of the 10 samples tested, HAE was the least cytotoxic toward BV2 microglia, with a half-maximal inhibitory concentration of 176.23 ± 2.64 mg/mL at 24 hours of incubation and 20.01 ± 1.69 mg/ mL at 48 hours of incubation. The inhibition of NO production was explored by pretreatment of BV2 microglia with samples at 2 incubation time points (4 and 24 hours) before the stimulation by LPS for 24 hours. After 24 hours of pretreatment, 8 of the 10 samples inhibited NO production by 50% or more, and cytotoxic effects were not observed. Among the 8 active samples, 500 µg/mL of HAE, 250 µg/mL of an n-butanol fraction of the HAE, and 250 µg/mL of an ethyl acetate fraction of HAE showed maximum inhibition of NO production by 88.95%, 86.50%, and 85.93%, respectively. These results suggest that the L. rhinocerotis sclerotium may contain secondary metabolites that have the potential to inhibit NO production.

Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice.

In this study, we investigated the antipsychotic-like effect of methanolic extract of Mitragyna speciosa leaf (MMS) using in vivo and ex vivo studies. In vivo studies comprised of apomorphine-induced climbing behavior, haloperidol-induced catalepsy, and ketamine-induced social withdrawal tests in mice whereas the ex vivo study was conducted utilizing isolated rat vas deferens preparation. Acute oral administration of MMS (50-500 mg/kg) showed an inverted bell-shaped dose-response in apomorphine-induced cage climbing behavior in mice. The effective inhibitory doses of MMS (75 and 100 mg/kg, p.o.) obtained from the apomorphine study was further tested on haloperidol (subcataleptic dose; 0.1 mg/kg, i.p.)-induced catalepsy in the mouse bar test. MMS (75 and 100 mg/kg, p.o.) significantly potentiated the haloperidol-induced catalepsy in mice. Interestingly, MMS at the same effective doses (75 and 100 mg/kg, p.o.) significantly facilitated the social interaction in ketamine-induced social withdrawal mice. Furthermore, MMS inhibited the dopamine-induced contractile response dose-dependently in the isolated rat vas deferens preparations. In conclusion, this investigation provides first evidence that MMS exhibits antipsychotic-like activity with potential to alleviate positive as well as negative symptoms of psychosis in mice. This study also suggests the antidopaminergic activity of MMS that could be responsible for alleviating positive symptoms of psychosis.

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. AIM OF THE STUDY: The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. MATERIALS AND METHODS: In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. RESULTS: No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. CONCLUSION: The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic.

Variation in Lingual Nerve Course: A Human Cadaveric Study.

The lingual nerve is a terminal branch of the mandibular nerve. It is varied in its course and in its relationship to the mandibular alveolar crest, submandibular duct and also the related muscles in the floor of the mouth. This study aims to understand the course of the lingual nerve from the molar area until its insertion into the tongue muscle. This cadaveric research involved the study of 14 hemi-mandibles and consisted of two parts: (i) obtaining morphometrical measurements of the lingual nerve to three landmarks on the alveolar ridge, and (b) understanding non-metrical or morphological appearance of its terminal branches inserting in the ventral surface of the tongue. The mean distance between the fourteen lingual nerves and the alveolar ridge was 12.36 mm, and they were located 12.03 mm from the lower border of the mandible. These distances were varied when near the first molar (M1), second molar (M2) and third molar (M3). The lingual nerve coursed on the floor of the mouth for approximately 25.43 mm before it deviated toward the tongue anywhere between the mesial of M1 and distal of M2. Thirteen lingual nerves were found to loop around the submandibular duct for an average distance of 6.92 mm (95% CI: 5.24 to 8.60 mm). Their looping occurred anywhere between the M2 and M3. In 76.9% of the cases the loop started around the M3 region and the majority (69.2%) of these looping ended at between the first and second molars and at the lingual developmental groove of the second molar. It gave out as many as 4 branches at its terminal end at the ventral surface of the tongue, with the presence of 2 branches being the most common pattern. An awareness of the variations of the lingual nerve is important to prevent any untoward complications or nerve injury and it is hoped that these findings will be useful for planning of surgical procedures related to the alveolar crest, submandibular gland/ duct and surrounding areas.

Aqueous extract of Senecio candicans DC induce liver and kidney damage in a sub-chronic oral toxicity study in Wistar rats.

Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P < 0.05) in serum uric acid, creatinine, aspartate transaminase (AST) and alanine transaminase (ALP) levels. Histological examination of liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use in traditional medicine.

Identification and in vitro Evaluation of Lipids from Sclerotia of Lignosus rhinocerotis for Antioxidant and Anti-neuroinflammatory Activities.

Lignosus rhinocerotis (Cooke) Ryvarden (Tiger milk mushroom) is traditionally used to treat inflammation triggered symptoms and illnesses such as cough, fever and asthma. The present study evaluated the in vitro antioxidant, cytotoxic and anti-neuroinflammatory activities of the extract and fractions of selerotia powder of L. rhinocerotis on brain microglial (BV2) cells. The ethyl acetate fraction had a total phenolic content of 0.30 ± 0.11 mg GAE/g. This fraction had ferric reducing capacity of 61.8 ± 1.8 mg FSE/g, ABTS·+ scavenging activity of 36.8 ± 1.8 mg TE/g and DPPH free radical scavenging activity of 21.8% ± 0.7. At doses ranging from 0.1 µg/mL - 100 µg/mL, the extract and fractions were not cytotoxic to BV2 cells. At 100 µg/mL, the crude hydroethanolic extract and the ethyl acetate fraction elicited the highest nitric oxide reduction activities of 68.7% and 58.2%, respectively. Linoleic and oleic acids were the major lipid constituents in the ethyl acetate fraction based on FID and GC-MS analysis. Linoleic acid reduced nitric oxide production and down regulated the expression of neuroinflammatory iNOS and COX2 genes in BV2 cells.

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

OBJECTIVE: To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. METHODS: Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. RESULTS: Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). CONCLUSION: H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

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.

Lignosus rhinocerotis (Cooke) Ryvarden mimics the neuritogenic activity of nerve growth factor via MEK/ERK1/2 signaling pathway in PC-12 cells.

The traditional application of the sclerotium of Lignosus rhinocerotis (tiger's milk mushroom) by the indigenous folks as tonic and remedy to treat a variety of ailments has been documented in Malaysia. Indigenous communities claimed to have consumed the decoction to boost their alertness during hunting. Mental alertness is believed to be related to neuronal health and neuroactivity. In the present study, the cell viability and neuritogenic effects of L. rhinocerotis sclerotium hot aqueous and ethanolic extracts, and crude polysaccharides on rat pheochromocytoma (PC-12) cells were studied. Interestingly, the hot aqueous extract exhibited neuritogenic activity comparable to NGF in PC-12 cells. However, the extracts and crude polysaccharides stimulated neuritogenesis without stimulating the production of NGF in PC-12 cells. The involvements of the TrkA receptor and MEK/ERK1/2 pathway in hot aqueous extract-stimulated neuritogenesis were examined by Trk (K252a) and MEK/ERK1/2 (U0126 and PD98059) inhibitors. There was no significant difference in protein expression in NGF- and hot aqueous extract-treated cells for both total and phosphorylated p44/42 MAPK. The neuritogenic activity in PC-12 cells stimulated by hot aqueous and ethanolic extracts, and crude polysaccharides of L. rhinocerotis sclerotium mimicking NGF activity via the MEK/ERK1/2 signaling pathway is reported for the first time.