Triterpenoids with neurotrophic activity from Ganoderma lucidum

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
Natural product research (Impact Factor: 0.92). 10/2011; 25(17):1607-13. DOI: 10.1080/14786419.2010.496367
Source: PubMed

ABSTRACT A new triterpenoid, 4,4,14α-trimethyl-5α-chol-7,9(11)-dien-3-oxo-24-oic acid (1), together with seven known triterpenoids, were isolated from the dried fruiting bodies of Ganoderma lucidum. Their structures were elucidated by extensive spectroscopic analyses. Bioassay results revealed that compounds 1 and methyl ganoderic acid B (5) had nerve growth factor-like neuronal survival-promoting effects, whereas compounds 1, and 4-7 showed brain-derived neurotrophic factor-like neuronal survival-promoting activities.

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    • "This agrees with the finding of Cheung et al. [25] who showed that Ganoderma extract contained NGF-like compounds that mediated the neuronal differentiation and elongation of rat pheochromocytoma (PC12) cells. The Ganoderma neuroactive constituents that accounted for neurite outgrowth activity are triterpenoids, such as lucidenic acid [26], 7-oxo-ganoderic acid Z, ganolucidic acid A, methyl ganoderic acid A, ganoderic acid S1, and 4,4,14α-trimethyl-5α-chol-7,9(11)-dien-3-oxo-24-oic acid [27]. Further, the water-soluble polysaccharides of G. lucidum were shown to significantly (p < 0.05) reduce neuronal cell death and apoptosis of rat primary cortical neurons (model of brain cerebral ischemia) induced by oxygen/glucose deprivation treatment [19]. "
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    ABSTRACT: 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. 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. 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. 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.
    BMC Complementary and Alternative Medicine 10/2013; 13(1):261. DOI:10.1186/1472-6882-13-261 · 2.02 Impact Factor
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    • "On-going studies show that the aqueous extract of P. giganteus contains bioactive secondary metabolites like sterols and triterpenes (unpublished data). These compounds are reported to have neutrophic NGF-like properties and caused neurite outgrowth activity in PC12 cells [40]. We have shown for the first time that P. giganteus extract can stimulate neurite outgrowth by using PC12 cell line model. "
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    ABSTRACT: 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. 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. 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. 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.
    BMC Complementary and Alternative Medicine 07/2012; 12(1):102. DOI:10.1186/1472-6882-12-102 · 2.02 Impact Factor
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    ABSTRACT: The metabolites and pharmacokinetics of ganoderic acid C2 (GAC2), a bioactive triterpenoid in Ganoderma lucidum in rat plasma were investigated by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Totally, ten minor phase I metabolites of GAC2 were characterized after oral administration of GAC2, on the basis of their mass fragmentation pathways or direct comparison with authentic compounds by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC-DAD-ESI-MS(n)), and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC-ESI-IT-TOF/MS) methods. Moreover, a rapid and specific method for quantification of GAC2 in rat plasma after oral administration was developed by using a liquid-liquid extraction procedure and HPLC-ESI-MS/MS analysis. It is the first time to report the metabolites and pharmacokinetics of GAC2.
    Journal of pharmaceutical and biomedical analysis 03/2013; 75:64-73. DOI:10.1016/j.jpba.2012.11.024 · 2.98 Impact Factor
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