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.

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.

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.

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.

Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism.

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.

Fingolimod affects gene expression profile associated with LPS-induced memory impairment.

Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal's brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.

Intrastrain comparison of the chemical composition and antioxidant activity of an edible mushroom, Pleurotus giganteus, and its potent neuritogenic properties.

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.

Inferior alveolar nerve injury resulting from different implant rotary instruments: An ex vivo comparative study in human cadaveric mandibles.

The present study aimed to evaluate the degree of nerve injury on inferior alveolar nerve (IAN) by different implant drills resulting from direct canal intrusion into inferior alveolar canal (IAC). A cadaveric study involving 7 human mandibles was performed to evaluate mechanical injury of canal enclosed IAN resulting from different drills. In group 1, osteotomies were created using different drills with 1 mm of intracanal intrusion, simulating accidental drill intrusion into canal. In group 2, drilling was stopped when the tip has breached into IAC, limited by tactile feedback of operator. The depth and width of nerve defects were assessed using optical coherence tomography. A significant difference in defect depth was found (p < 0.001) in group 1. A sinus lift reamer inflicted the least damage (0.068 ± 0.022 mm). It was also found that the mean defect depth was significantly different when a twist drill was used (p = 0.016). Sinus lift reamer can be used safely for osteotomy preparation in mandible when bone height is limited or when radiographic visualization of canal is poor. Bone corticalization around IAC does not provide adequate protection for IAN in the event of accidental intracanal intrusion.

Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3.

BACKGROUND: 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. METHODS: The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments. In vitro cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively. RESULTS: Aqueous extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and Grifola frondosa; as well as an ethanol extract of Cordyceps militaris significantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 ± 4.2%, 38.1 ± 2.6%, 33.4 ± 4.6%, 33.7 ± 1.5%, and 35.8 ± 3.4%; respectively. The IC50 values obtained from tetrazolium (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts. CONCLUSION: Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa and C. militaris may be developed as safe and healthy dietary supplements for brain and cognitive health.

Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochromocytoma cells.

BACKGROUND: Senescence of the neurons is believed to be a focal factor in the development of age-related neurodegenerative diseases such as Alzheimer's disease. Diminutions in the levels of nerve growth factor (NGF) lead to major declines in brain cell performance. Functional foods, believed to mitigate this deficiency, will be reaching a plateau in the near future market of alternative and preventive medicine. In the search for neuroactive compounds that mimic the NGF activity for the prevention of neurodegenerative diseases, the potential medicinal values of culinary and medicinal mushrooms attract intense interest. METHODS: Cytotoxic effects of aqueous extracts of three medicinal mushrooms basidiocarps, Ganoderma lucidum, Ganoderma neo-japonicum and Grifola frondosa towards rat pheochromocytoma (PC-12) cells were determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The potentiation of neuritogenic activity was assessed by neurite outgrowth stimulation assay. Involvement of cellular signaling pathways, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) in mushrooms-stimulated neuritogenesis were examined by using specific pharmacological inhibitors. Alteration of neuronal morphology by inhibitors was visualized by immunofluorescence staining of the neurofilament. RESULTS: All the aqueous extracts tested caused a marked stimulation of neuritogenesis with no detectable cytotoxic effects towards PC-12 cells. The aqueous extract of G. neo-japonicum triggered maximal stimulation of neurite outgrowth at a lower concentration (50 µg/ml) with 14.22 ± 0.43% of neurite-bearing cells, compared to G. lucidum and G. frondosa that act at a higher concentration (75 µg/ml), with 12.61 ± 0.11% and 12.07 ± 0.46% of neurite-bearing cells, respectively. The activation of MEK/ERK1/2 and PI3K/Akt signaling pathways were necessary for the NGF and aqueous extracts to promote neuritogenesis. CONCLUSIONS: Ganoderma lucidum, G. neo-japonicum and G. frondosa may contain NGF-like bioactive compound(s) for maintaining and regenerating the neuronal communications network. The present study reports the first evidence of the neuritogenic effects of aqueous extracts of basidiocarps of G. neo-japonicum in-vitro and showed the involvement of MEK/ERK1/2 and P13K/Akt signaling pathways for neuritogenesis in PC-12 cells.

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.

Lignosus rhinocerus (Cooke) Ryvarden: A Medicinal Mushroom That Stimulates Neurite Outgrowth in PC-12 Cells.

A national treasure mushroom, Lignosus rhinocerus, has been used to treat variety of ailments by local and indigenous communities in Malaysia. The aim of this study was to investigate the potential of the most valuable part of L. rhinocerus, the sclerotium, on neurite outgrowth activity by using PC-12Adh cell line. Differentiated cells with one thin extension at least double the length of the cell diameter were scored positive. Our results showed that aqueous sclerotium L. rhinocerus extract induced neurite outgrowths of 24.4% and 42.1% at 20 µg/mL (w/v) of aqueous extract alone and a combination of 20 µg/mL (w/v) aqueous extract and 30 ng/mL (w/v) of NGF, respectively. Combination of NGF and sclerotium extract had additive effects and enhanced neurite outgrowth. Neuronal differentiation was demonstrated by indirect immunofluorescence of neurofilament protein. Aqueous sclerotium extract contained neuroactive compounds that stimulated neurite outgrowth in vitro. To our knowledge this is the first report on neurite-stimulating activities of L. rhinocerus.

Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.

BACKGROUND: 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. METHODS: The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. RESULTS: The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 µg/ml of aqueous extract and 15 µg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. CONCLUSIONS: P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be developed as a nutraceutical for the mitigation of neurodegenerative diseases.

Neuroregenerative potential of lion's mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (higher Basidiomycetes), in the treatment of peripheral nerve injury (review).

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.

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.

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.

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

Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

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.

The role of cells, neurotrophins, extracellular matrix and cell surface molecules in peripheral nerve regeneration.

Wallerian degeneration is a complicated process whereby axons and myelin sheaths undergo degeneration, and eventually are phagocytosed by macrophages and Schwann cells following nerve damage. Schwann cells proliferate and the endoneural tubes persist. In addition, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The important role of cellular components, neurotrophins, and extracellular matrix components, including cell surface molecules involved in this regenerative process, is highlighted and discussed in this review.

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.