RESUMO
ETHNOPHARMACOLOGY RELEVANCE: Ganoderma leucocontextum T.H. Li, W. Q. Deng M. Wang & H.P.Hu. is a highland herbal medicine that has been shown to nourish the nervesand prolong life. Nevertheless, there is no evidence to indicate that Ganoderma leucocontextum triterpenoids (GLTs) reduce the damage triggered by Alzheimer's disease (AD). AIM OF THE STUDY: The aim of this investigation was to ascertain the protective effects of GLTs on AD mice models and cells, as well as to look into potential pathways. MATERIALS AND METHODS: In this study, the phytochemical characterization of GLTs was performed by High Performance Liquid Chromatography (HPLC) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). The AD mouse model was induced by injecting intraperitoneally with D-galactose (120 mg/kg) and administering orally with aluminum chloride (20 mg/kg) daily for 28 days. After that, donepezil (5 mg/kg) and GLTs (0.4, 0.8, and 1.6 g/kg) were administered orally for 35 days. During the treatment period, aluminum chloride (20 mg/kg) and D-galactose (120 mg/kg) were continuously administered. And the behavior of the animals and the molecular changes of the hippocampus were determined after the whole experimental procedure. Furthermore, BV-2 cells were employed to validate GLTs' anti-neuroinflammatory properties. RESULTS: The total triterpenoids content was 443.12 ± 0.21g/kg and was inferred to contain 19 classes of substances such as organic acids, amino acids, vitamins, flavonoids, and other chemicals in GLTs. Treatment of D-galactose/aluminum chloride-induced mouse with GLTs can ameliorate AD symptoms, counteract cognitive decline, improve Aß1-42 deposition, reduce the expression level of pro-apoptotic proteins, and attenuate the activation of hippocampal microglia and astrocytes. GLTs significantly increased the expression of antioxidant enzymes and significantly reduced the expression of inflammatory factors. GLTs inhibits nuclear factor kappa B (NF-κB) nuclear translocation and preserves myd88/traf6-mediated mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, GLTs (2 and 5mg/mL) inhibited the generation of nitric oxide and protected lipopolysaccharide (1mg/L)-induced neuroinflammation in BV-2 cells. CONCLUSIONS: Taken together, Ganoderma leucocontextum triterpenoids can improve cognitive functions, including learning and memory, by reducing neuroinflammation and oxidative stress, preventing apoptosis, and controlling amyloid genesis.
RESUMO
Ganoderma leucocontextum is a well-known traditional medicine in Tibet Autonomous Region, which has benefits, such as anti-hypoxia, neurotrophic action on nerves, easing coughs and relieving asthma, strengthening the body and prolonging life. However, few research have focused on its negative effects, possibly jeopardizing its safety. The purpose of this study is to evaluate the acute and subacute toxicity of an alcoholic extract from G. leucocontextum (GLA) in vivo. The phytochemical characterization analysis showed that alcoholic extract from G. leucocontextum were rich in polysaccharides, triterpenoids. Then, in acute oral toxicity, male and female mice from Institute of Cancer Research (ICR) were orally administered with 16 g/kg GLA and were observed for 14 days. In the subacute toxicity, male and female Sprague-Dawley (SD) rats were orally administered with 2, 4, and 8 g/kg doses of GLA for 28 days. There was no death or clinical changes in male and female mice in the acute toxicity test. During the subacute toxicity test, the difference in body weights, food consumption, biochemical and hematological parameters, and organ coefficients between treated and control groups were unrelated to GLA treatment. The obtained data show that the GLA had no significant toxic effects when administered orally to male and female rats in acute and subacute toxicity.
