Prevention Of Neurodegenerative Diseases Research Articles

Repurposing of Nitroxoline Drug for the Prevention of Neurodegeneration.

Oxidative stress has been documented as one of the significant causes of neurodegenerative diseases. Therefore, antioxidant therapy for the prevention of neurodegenerative diseases seems to be an interesting strategy in drug discovery. The quinoline-based compound, namely 5-nitro-8-quinolinol (NQ), has shown excellent antimicrobial, anticancer, and anti-inflammatory activities. However, its neuroprotective effects and precise molecular mechanisms in human neuronal cells have not been elucidated. In this work, the effects of NQ on cell viability and morphology were evaluated by the MTT assay and microscopic observation. Moreover, the underlying mechanisms of this compound, inducing the survival rate of neuronal cells under oxidative stress, were investigated by reactive oxygen species (ROS) assay, flow cytometry, Western blotting, and immunofluorescence techniques. In addition, the molecular interaction of sirtuin1 (SIRT1) with NQ was constructed using the AutoDock 4.2 program. Interestingly, NQ protected SH-SY5Y cells against H2O2-induced neurotoxicity through scavenging ROS, upregulating the levels of SIRT1 and FOXO3a, increasing the levels of antioxidant enzymes (catalase and superoxide dismutase), promoting antiapoptotic BCL-2 protein expression, and reducing apoptosis. Besides, molecular docking also revealed that NQ interacted satisfactorily with the active site of SIRT1 similar to the resveratrol, which is the SIRT1 activator and strong antioxidant. These findings suggest that NQ prevents oxidative-stress-induced neurodegeneration because of its antioxidant capacity as well as antiapoptotic property through SIRT1-FOXO3a signaling pathway. Thus, NQ might be a drug that could be repurposed for prevention of neurodegeneration.

An Overview of the Cardiorespiratory Hypothesis and Its Potential Contribution to the Care of Neurodegenerative Disease in Africa

One hypothesis that could explain the beneficial effects of physical exercise on cognitive function is the cardiorespiratory hypothesis. This hypothesis proposes that improved cognitive functioning may be in part a result of the physiological processes that occur after physical exercise such as: Increased cerebral perfusion and regional cerebral blood flow. These processes ensure increased oxygenation and glucose transportation to the brain, which together can improve cognitive function. The objective of this narrative review is to examine the contribution of this hypothesis in the care of African older adults with neurodegenerative conditions (i.e., dementia (Alzheimer’s disease)) or with mild cognitive impairments. Although studies in developed countries have examined people of African descent (i.e., with African Americans), only the limited findings presented in this review reflect how these conditions are also important for the African continent. This review revealed that no studies have examined the effects of cardiorespiratory fitness on neurodegenerative disease in Africa. African nations, like many other developing countries, have an aging population that is growing and will face an increased risk of neurodegenerative declines. It is therefore imperative that new research projects be developed to explore the role of the cardiorespiratory fitness in neurodegenerative disease prevention in African nations.

Cyanidin-3-O-Glucoside Protects PC12 Cells Against Neuronal Apoptosis Mediated by LPS-Stimulated BV2 Microglial Activation.

Neuroinflammation is a major factor in the pathogenesis of various neurodegenerative diseases. Microglia are resident macrophages that act as key mediators of inflammation in the brain. In response to inflammatory stimuli including lipopolysaccharide (LPS), microglial activation occurs immediately. Overproduction of inflammatory mediators released by activated microglia contributes to neuron damage in neurodegenerative disease. Therefore, identification of a compound that has anti-inflammatory activities and inhibits microglial activation may be an alternative therapeutic approach for the treatment of neurodegenerative diseases. Cyanidin-3-O-glucoside (C3G), a type of anthocyanin, possesses powerful anti-inflammatory activities. In this study, the anti-inflammatory effects of C3G were investigated in LPS-stimulated BV2 microglia. The results indicate that pretreatment with C3G significantly suppresses microglial activation and the production of neurotoxic mediators including nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6) in LPS-activated BV2 cells. Moreover, C3G downregulates the gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines via the suppression of NF-κB and p38 MAPK signaling pathways. Furthermore, a co-culture system to determine the indirect neuroprotective effects of C3G was used. Results demonstrated that conditioned medium (CM) from LPS-stimulated BV2 cells can promote the apoptosis of differentiated pheochromocytoma (PC12) cells through the activation of caspase-3, while C3G pretreatment in BV2 microglia can protect differentiated PC12 cells from microglial activation-induced apoptosis. Therefore, C3G may be a potential therapeutic agent for the treatment and prevention of neurodegenerative diseases associated with microglial activation.

Neuroprotective Effects of Ginseng Phytochemicals: Recent Perspectives.

As our global population ages, the treatment of neurodegenerative diseases is critical to our society. In recent years, researchers have begun to study the role of biologically active chemicals from plants and herbs to gain new inspiration and develop new therapeutic drugs. Ginseng (Panax ginseng C.A. Mey.) is a famous Chinese herbal medicine with a variety of pharmacological activities. It has been used to treat various diseases since ancient times. Extensive research over the years has shown that ginseng has potential as a neuroprotective drug, and its neuroprotective effects can be used to treat and prevent neurological damage or pathologically related diseases (such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, depression symptoms, and strokes). Moreover, evidence for the medicinal and health benefits of ginsenoside, its main active ingredient, in the prevention of neurodegenerative diseases is increasing, and current clinical results have not reported any serious adverse reactions to ginseng. Therefore, we briefly review the recent research and development on the beneficial effects and mechanisms of ginseng and its main active ingredient, ginsenoside, in the prevention and treatment of neurodegenerative diseases, hoping to provide some ideas for the discovery and identification of ginseng neuroprotection.

Melatonin: Clinical Perspectives in Neurodegeneration.

Prevention of neurodegenerative diseases is presently a major goal for our Society and melatonin, an unusual phylogenetically conserved molecule present in all aerobic organisms, merits consideration in this respect. Melatonin combines both chronobiotic and cytoprotective properties. As a chronobiotic, melatonin can modify phase and amplitude of biological rhythms. As a cytoprotective molecule, melatonin reverses the low degree inflammatory damage seen in neurodegenerative disorders and aging. Low levels of melatonin in blood characterizes advancing age. In experimental models of Alzheimer's disease (AD) and Parkinson's disease (PD) the neurodegeneration observed is prevented by melatonin. Melatonin also increased removal of toxic proteins by the brain glymphatic system. A limited number of clinical trials endorse melatonin's potentiality in AD and PD, particularly at an early stage of disease. Calculations derived from animal studies indicate cytoprotective melatonin doses in the 40–100 mg/day range. Hence, controlled studies employing melatonin doses in this range are urgently needed. The off-label use of melatonin is discussed.

Effects of Carpobrotus edulis Extract on Oxidative Stress and 158N Oligodendrocyte Death

ObjectiveAge-related diseases, including neurodegenerative diseases, are associated with oxidative stress and lipid peroxidation, and increase the levels of cholesterol auto-oxidation products such as 7β-hydroxycholesterol (7β-OHC). Thus, it is imperative to identify agents that can prevent 7β-OHC-induced side-effects. MethodsWe evaluated the potential protective effects of Carpobrotus edulis ethanol-water extract (EWe) on murine oligodendrocytes (158N) cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h). The cells were incubated with EWe (20-200 µg/mL) 2 h before 7β-OHC treatment. Mitochondrial activity and cell growth were evaluated with the MTT assay. Photometric methods were used to analyze antioxidant enzyme [catalase (CAT) and glutathione peroxidase (GPx)] activities and the generation of lipid and protein oxidation products [malondialdehyde (MDA), conjugated diene (CD), and carbonylated proteins (CPs)]. ResultsTreatment with 7β-OHC induced cell death and oxidative stress (reflected by alteration in CAT and SOD activities). Overproduction of lipid peroxidation products (MDA and CDs) and CPs was also reported. The cytotoxic effects associated with 7β-OHC were attenuated by 160 μg/mL of EWe of C. edulis. Cell death induced by 7β-OHC treatment was ameliorated, GPx and CAT activities were restored to normal, and MDA, CD, and CP levels were reduced following C. edulis extract treatment. ConclusionThese data demonstrate the protective activities of C. edulis EWe against 7β-OHC-induced disequilibrium in the redox status of 158N cells, indicative of the potential role of this plant extract in the prevention of neurodegenerative diseases.

Significance of Antioxidants in the Treatment and Prevention of Neurodegenerative Diseases

Neurodegenerative diseases are ailments that disturb the brain, precisely the neurons. The utmost mutual indicators include failures in stability, inhalation, movement, reflexes, motor skills or heartbeat activity. These can be prevented using ordinary antioxidants, like vitamins E and C, flavonoids, and polyphenols compounds. Antioxidants show a substantial effect in human’s health since they can ameliorate aging by fighting free radicals. Precisely Vitamin C can serve as a commanding antioxidant in reducing the consequence of oxidative injury triggered by pollutants, anxiety and poor diets amongst others. Thereby reducing the long-term risk of neurodegenerative diseases. Currently, neurodegenerative diseases have no cure, but they can be managed. This diseases management reduces the symptoms so as to sustain the value of life. Management with natural antioxidants such as polyphenols through diet or dietary supplements with lots of benefits have become an attractive alternative. The present knowledge on antioxidant in the treatment of neurodegenerative disorders and future bearings will be discussed and also assess the value for antioxidants as neuroprotective.

Auraptene/Naringin-Rich Fruit Juice of Citrus kawachiensis (Kawachi Bankan) Prevents Ischemia-Induced Neuronal Cell Death in Mouse Brain through Anti-Inflammatory Responses.

Cerebral ischemia/reperfusion leads to delayed neuronal cell death, resulting in brain damage. Auraptene (AUR) and naringin (NGIN), which exert neuroprotective effects in ischemic brain, are abundant in the peel of Citrus kawachiensis. Although parts of AUR/NGIN are transited from the peel to the juice during the squeezing of this fruit, these amounts in juice might be too low to exert effects. We thus prepared the AUR/NGIN-rich fruit juice of C. kawachiensis by addition of peel paste to the raw juice. The present study revealed that orally administration of the dried powder of this AUR/NGIN-rich fruit juice (2.5 g/kg/d) for 7 d to ischemic mice significantly suppressed the ischemia-induced neuronal cell death in the hippocampus, which was coincidently with the reduction of hyperactivation of microglia and astrocytes. These results suggest that AUR/NGIN-rich juice of C. kawachiensis may possess therapeutic potential for the prevention of neurodegenerative diseases via inhibition of inflammatory processes.

Protective effect of ethyl vanillin against Aβ-induced neurotoxicity in PC12 cells via the reduction of oxidative stress and apoptosis.

Increased aggregation of β-amyloid (Aβ) peptides induces oxidative stress, which is considered a major contributor in the development of Alzheimer's disease (AD). Prevention of Aβ-induced neurotoxicity is proposed as a possible modality for treatment of AD. The present study aimed to elucidate possible effects of ethyl vanillin (EVA), an analog of vanillin isolated from vanilla beans, on the Aβ1-42-induced oxidative injury in PC12 cells. EVA restrained the decrease in PC12 cell viability and apoptosis induction caused by treatment with Aβ1-42. In addition, EVA markedly alleviated intracellular lipid peroxidation as demonstrated by malondialdehyde levels and reactive oxygen species production in Aβ1-42-treated PC12 cells. In addition, the reduction in the activity levels of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase was detected in Aβ1-42-treated PC12 cells. This effect was partially reversed by treatment with EVA. Furthermore, the results indicated that EVA attenuated Aβ1-42-induced caspase-3 activation and the increase noted in the apoptosis regulator Bcl-2/apoptosis regulator Bax ratio of PC12 cells. These results indicated that EVA could be used as an efficient and novel agent for the prevention of neurodegenerative diseases via inhibition of oxidative stress and cell apoptosis.

Inhibition of LPS induced neurochemical imbalance and oxidative stress by pigmented and non-pigmented rice bran extracts.

This study evaluated the neuroprotective efficacy of the pigmented and non-pigmented rice bran extract, against LPS induced neurotransmitter imbalance and oxidative stress markers. Male wistar rats were orally supplemented with 2% ethanolic rice bran extracts daily for two weeks. On the last day of experiment, rats were challenged intraperitoneally (i.p) with LPS for 4 hr. LPS exposure resulted in the elevation of malondialdehyde and nitrite levels, decreased GSH, increased antioxidant enzymes activity and led to imbalance in neurotransmitters, norepinephrine, dopamine and serotonin and their metabolites 3,4-dihydroxyphenylacetic acid, homovanillic levels and acetylcholinesterase activity. Pre-treatment with rice bran extracts significantly attenuated LPS induced oxidative stress by improving the antioxidant systems, acetylcholinesterase activity and neurotransmitters imbalance with the higher potency for pigmented bran extracts. The findings suggest the possibility of utilization of pigmented bran extract for the prevention of neurodegenerative diseases and promote the overall good health of the brain. PRACTICAL APPLICATION: Present study provides the current evidence for the neuroprotective efficacy of bran extracts from pigmented and non-pigmented rice. These findings indicate the beneficial effects of pre-treatment of rice bran extracts on LPS induced oxidative stress and neurochemical imbalance by improvement in the antioxidant machinery and neurotransmitters level. This study emphasizes the possibility of utilization of pigmented bran extract as a food ingredient to improve the overall brain health.

In vitro screening for acetylcholinesterase and butyrylcholinesterase inhibition and antimicrobial activity of chia seeds (Salvia hispanica)

Chia seeds are gaining increasing interest among food producers and consumers because of their prohealth properties. The aim of this work was to evaluate the potential of chia seeds to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The highest inhibitory activity against AChE and BChE was observed for colored seed ethanol extracts. A positive correlation was found between the presence of quercetin and isoquercetin as well as protocatechuic, hydroxybenzoic, and coumaric acids and the activity of extracts as AChE and BChE inhibitors. It has also been shown that grain fragmentation affects the increase in the activity of seeds against cholinesterases (ChE). Furthermore, seeds have been shown to be a source of substances that inhibit microbial growth. It was found that the chia seed extracts are rich in polyphenols and inhibit the activity of ChEs; therefore, their use can be considered in further research in the field of treatment and prevention of neurodegenerative diseases. How to cite: Kobus-Cisowska J, Szymanowska D, Maciejewska P, et al. In vitro screening for acetylcholinesterase and butyrylcholinoesterase inhibition and antimicrobial activity of chia seeds (Salvia hispanica). Electron J Biotechnol 2019;37. https://doi.org/10.1016/j.ejbt.2018.10.002

Exploring the Benefits of Cellular Models to Uncover Bioactive Polyphenols for Neurodegeneration

Our society is currently experiencing increased lifespan; one of the top causes for the high incidence of neurodegenerative disorders. The lack of effective treatments delaying or blocking disease progression has encouraged the active search for novel therapies. Many evidences support the protective role of phytochemicals in the prevention of neurodegenerative diseases, particularly (poly)phenols. In this review, we described the use of cellular-based models of neurodegenerative diseases and the benefits of their use as potent tools in the search for bioactive molecules, particularly (poly)phenols. Studies to assess the biological activity of (poly)phenols involve experimentation with in vitro and in vivo systems. In vitro systems are a useful tool as a first approach to test the underlined molecular mechanisms of candidate molecules. They can provide valuable information about biological activity, which can be then used to design animal and human intervention studies.

Sesamin suppresses LPS-induced microglial activation via regulation of TLR4 expression

Sesamin, one of the most abundant lignans in sesame seeds and oils, is well known for neuroprotective activity. However, its effects on toll-like-receptor 4 (TLR4), the key innate immune receptor implicated in microglia activation and neuroinflammation has not been reported. Our study demonstrated that sesamin significantly diminished LPS-stimulated TLR4 expression result in the reduction of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in BV2 microglia by suppressing JNK and NF-κB pathway. While conditioned medium from LPS-stimulated microglia-induced PC12 cell death, sesamin pre-treatment on microglia abrogated the cytotoxic effects of pro-inflammatory mediators. Our result also demonstrated the direct effect of sesamin in ameliorating PC12 cell death induced by activated microglial-conditioned medium. These results suggested that sesamin alleviated inflammation-induced neurodegeneration via inhibition of TLR4 expression and microglial activation resulting in diminishing the neurotoxicity effect. Sesamin might be a potential agent for neurodegenerative diseases prevention.

Neuroprotective Mechanisms of Orientin against Hydrogen Peroxide-induced Oxidative Damage in SH-SY5Y Cells

Natural products or plant derivatives could be used to prevent or treat neurodegenerative diseases (ND). Oxidative stress has been highly implicated in the progression of ND;thus, this leads to the study on the effects of orientin in regulating Nrf2/Keap-1 redox signalling, PI3K/Akt survival and MAPK/ERK apoptosis pathways in the hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells. The cells were treated with half maximum non-toxic dose (½ MNTD) or maximum non-toxic dose (MNTD) of orientin and subsequently with H2O2. Cells were then subjected to the measurement of nitric oxide (NO), intracellular calcium (Ca2+), mitochondrial membrane potential (MMP) and annexin V/propidium iodide apoptosis assays. Regulation of the signalling pathways was analysed by Western blotting. Results showed that ½ MNTD of orientin reduced the NO levels. The intracellular Ca2+ level was also reduced by ½ MNTD and MNTD of orientin. The orientin treatment at ½ MNTD and MNTD restored the loss of MMP. Pre-treatment of orientin reduced the early and late apoptotic cells as well as necrotic cells. Orientin was found to up-regulate the Nrf2/Keap-1 and PI3K/Akt pathways whilst down-regulate the MAPK/ERK pathway. The findings from this study will be useful for the prevention of ND in the near future.
 
 

7β-hydroxycholesterol-induced cell death, oxidative stress, and fatty acid metabolism dysfunctions attenuated with sea urchin egg oil

Some oxysterols resulting either from enzymatic oxidation or autoxidation of cholesterol are associated with age-related diseases including neurodegenerative diseases. Among these oxysterols, 7β-hydroxycholesterol (7β-OHC) is often found at increased levels in patients. It is therefore important to identify molecules or mixtures of molecules to prevent 7β-OHC-induced side effects. Consequently, murine oligodendrocytes (158N) were cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h) with or without a natural oil extracted from sea urchin (Paracentrotus lividus) eggs known for its biological activity. Firstly, the chemical composition of this oil was determined using 31P NMR and GC-MS. Secondly, this oil was used to reduce 7β-OHC-induced side effects. To this end, the oil (160 μg/mL) was added to the culture medium of 158N cells 2 h before 7β-OHC. The effects of 7β-OHC with or without the oil on cell viability were studied with the MTT test. Photometric methods were used to analyze antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation product (carbonylated proteins (CPs)). Gas chromatography was used to determine the fatty acid profile. With 7β-OHC, an induction of cell death associated with oxidative stress (alteration of GPx and SOD activities) was observed; an overproduction of lipid peroxidation products (MDA and CDs) and CPs was also revealed. Sea urchin egg oil attenuated 7β-OHC-induced cytotoxicity: 7β-OHC-induced cell death was reduced, GPx and SOD activities were normalized, and lower levels of MDA, CDs and CPs were produced. In addition, whereas a disturbed fatty acid profile was observed with 7β-OHC, similar fatty acid profiles were found in control cells and in cells cultured with 7β-OHC associated with sea urchin egg oil. These data demonstrate the protective activities of sea urchin egg oil against 7β-OHC-induced side effects on 158N cells, supporting the concept that this oil may have benefits in the prevention of neurodegenerative diseases.

Association of objectively measured physical activity with brain structure: UK Biobank study.

Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. We used data from UK Biobank (n = 5272; aged 55.4 ± 7.5 years; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for 7 days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain. There was an association between physical activity (per SD increase) and grey matter volume after adjustment for a range of covariates, although this association was only detected in older adults (>60 years old). We also observed associations of physical activity with both left (B = 0.52, 95% CI, 0.01, 1.03; P = 0.046) and right hippocampal volume (B = 0.59, 95% CI, 0.08, 1.10; P = 0.024) in covariate-adjusted models. In summary, physical activity may play a role in the prevention of neurodegenerative diseases.

The benefits of physical activities on cognitive and mental health in healthy and pathological aging.

Aging is associated with a decreased efficiency of different cognitive functions as well as in the perceptive, physical and physiological changes. The age-related cognitive decline concerns mainly attention, executive control and episodic memory. Some factors such as being physically active protect against the age-related decline. This review will discuss how physical activity can positively affect the cognitive efficiency and mental health of older healthy individuals, and possibly reduces the risk of progression into dementia, and depression. Underlying neurophysiological mechanisms play an important role for improving attention and episodic memory, which are the most sensitive to the effects of aging. We also present recommendations for the management of physical activity for the prevention of cognitive deficits, and the reduction of depressive symptoms in older persons. Given the benefits of physical activity for the prevention of neurodegenerative disease and the improvement of the well-being, it appears to be an important low cost therapeutic approach that should be integrated into clinical practice.

In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea.

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3-O-gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative properties. Furthermore, several lines of evidence have indicated that the binding affinity of EGCG to specific proteins may explain its mechanism of action. This review article aims to reveal how EGCG-protein interactions can explain the mechanism by which green tea/EGCG can exhibit health beneficial effects. We conducted a literature search, using mainly the PubMed database. The results showed that several methods such as dot assays, affinity gel chromatography, surface plasmon resonance, computational docking analyses, and X-ray crystallography have been used for this purpose. These studies have provided evidence to show how EGCG can fit or occupy the position in or near functional sites and induce a conformational change, including a quaternary conformational change in some cases. Active site blocking, steric hindrance by binding of EGCG near an active site or induced conformational change appeared to cause inhibition of enzymatic activity and other biological activities of proteins, which are related to EGCG’s biological oligomer and formation of their toxic aggregates, leading to the prevention of neurodegenerative diseases and amyloidosis. In conclusion, these studies have provided useful information on the action of green tea/catechins and would lead to future studies that will provide further evidence for rational EGCG therapy and use EGCG as a lead compound for drug design.

Natural or Plant Products for the Treatment of Neurological Disorders: Current Knowledge.

In recent decades, complementary and alternative medicine (CAM) has become very popular in the treatment of several chronic diseases. Natural products as one of the CAM modalities offer potential opportunities to discover lead compounds for novel drug development. The use of CAM or natural products in the prevention of neurodegenerative diseases is comparatively a newer area. A structured online literature search for peer-reviewed research articles was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals, using phrases: natural products for neurologic disorders, phytomedicine for neurodegenerative diseases, natural therapeutics for neurological symptopms etc. Results: The retrieved data showed the natural therapeutics with anti-oxidative and anti-inflammatory salutations evidently plays a crucial role in protecting neurons. Of these, the most promising are caffeine, trigonelline, shogaol, curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones, withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white willow bark, including Chinese formulations Renshen Shouwu and Shengmai San. Though several herbs and their active ingredients have been studied in laboratory and clinical settings, only a few have been investigated for their molecular mechanisms of action. Notably, despite the promising and safe therapeutic benefits of CAM/herbal medicines, there exists a possible risk when combining them with prescription drugs. As a result, many drugs have shown changes in blood pressure, hepatotoxicity, seizures etc. when combined with certain herbs. Certainly, extensive work is needed to make sure that patients should take a regimen of protective and restorative therapy under an experienced healthcare professional. This article updates on the current knowledge of promising natural products used in neurological disorders.

Triterpenes and Meroterpenes with Neuroprotective Effects from Ganoderma leucocontextum.

Ganoderma leucocontextum is a well-known medicinal mushroom cultivated in the Tibet Plateau of China. Chemistry investigation on the fruiting bodies of this mushroom resulted in the isolation of sixteen secondary metabolites including three new lanostane triterpenes, ganoleucoins Q - S (1 - 3), as well as thirteen known compounds (4 - 16). The structures of compounds 1 - 3 were determined by NMR, MS, CD spectral analysis, and chemical derivation method. The neuroprotective effects of compounds 1 - 16 were tested on PC12 cells. Compounds 1 and 2 showed protective effects against the H2 O2 induced damage with the survival rate of 83.19 ± 0.92%, 73.37 ± 1.25% at the concentration of 200 μm, respectively. Meanwhile, compounds 1 and 2 induced neurite outgrowth at 50 - 200 μm. The results from this study suggested that G. leucocontextum and its metabolites may be potential functional food ingredients for the prevention of neurodegenerative diseases.