Alkaloids enriched extract from Dendrobium nobile Lindl. attenuates tau protein hyperphosphorylation and apoptosis induced by lipopolysaccharide in rat brain.

Neurofibrillary tangles, one of the characteristic pathological features of Alzheimer's disease (AD), are composed of paired helical filaments mainly with hyperphosphorylated tau protein. Inhibition of the hyperphosphorylation of tau protein is an effective therapy for AD. The current study was designed to investigate the protective effects of alkaloids enriched extract from Dendrobium Nobile Lindl. (EDNLA), a Chinese medicinal herb, on hyperphosphorylation of tau protein in AD brain. Rats were administrated intragastrically with different doses of DNLA (20, 40 mg/kg) every 8h for one day, followed by lipopolysaccharide (LPS, 100 μg) injecting into the bilateral ventricle. Two hours later, the hippocampi of each group were collected to examine the hyperphosphorylated tau protein by western blotting. Additional rats were treated by EDNLA thrice daily for one week, to examine the effects on LPS-induced apoptosis in the brain. LPS injection significantly increased the expression of hyperphosphorylated tau protein at Ser396, Ser199-202, Ser404, Thr231, Thr205 sites and GSK-3β increased, LPS also induced apoptosis in the brain. EDNLA dramatically ameliorated these abnormal changes (P<0.05). The present study demonstrated that EDNLA attenuates LPS-induced hyperphosphorylation of tau protein in rat's hippocampus and protects against LPS-induced apoptosis in rat brain.

Yang S ，Gong Q ，Wu Q ，Li F ，Lu Y ，Shi J ... -  《-》

Dendrobium nobile Lindl. alkaloid decreases Tau hyperphosphorylation via regulating PI3K/Akt/GSK-3β pathway in vitro and in vivo.

Huang J ，Huang N ，Qiu Y ，Shi J ... -  《-》

Inhibitory effects of Dendrobium alkaloids on memory impairment induced by lipopolysaccharide in rats.

Dendrobium alkaloids (DNLA), extracted from Dendrobium nobile Lindl. whose botanical name is Dendrobium moniliforme, Orchidaceae family, were studied for their effect on lipopolysaccharide (LPS)-induced memory impairment in rats. SD rats were pretreated with DNLA (40, 80, 160 mg/kg/d for 7 d), followed by LPS (50 µg) injection into the right lateral ventricle to produce memory impairment. DNLA treatment continued for another 13 days. The spatial behavior was tested by the Morris water maze; the level of tumor necrosis factor receptor 1 (TNFR1) mRNA was detected by real time RT-PCR, and the protein level of TNFR1, nuclear factor kappa-B (NF- κB) and phosphorylated p38 mitogen-activated protein kinases (p-p38 MAPK) by Western blotting. The results showed that DNLA significantly improved the neurobehavioral performance and prevented LPS-induced elevation in TNFR1 mRNA and protein levels. LPS-induced activation of p38 MAPK and NF- κB pathway was also suppressed. In conclusion, DNLA is effective in protecting against LPS-induced brain impairment, and this effect is due, at least in part, to prevent overexpression of TNFR1 via inhibition of p-p38 MAPK and the downstream NF- κB signal pathway.

Li Y ，Li F ，Gong Q ，Wu Q ，Shi J ... -  《-》

Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats.

Ginkgo biloba extract EGb761 has shown the neuroprotective effects on Alzheimer's disease (AD) through the protection against the Aβ-induced neurotoxicity. However, it is not completedly clear whether EGb761 attenuates tau hyperphosphorylation, another of the most prominent mechanisms underlying the pathology of AD. we employed hyperhomocysteinemia (HHcy) to mimic AD like pathological alterations and memory deficits in rats as model, and injected EGb761 with or after HHcy injection as prevention and treatment, injected saline as control. We measured the status of oxidative damage and spatial and learning memory in rats. Then we detected the level of memory-related proteins, tau phosphorylation and the level and activity of tau kinase (GSK-3β) and phosphatase (PP2A) by Western blotting and Immunohistochemistry. We found that EGb761 could significantly antagonize HHcy-induced oxidative damage, recover PP2Ac and GSK3β activities deregulated by HHcy. Furthermore, tau was hyperphosphorylated at Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and GSK3β targeted sites in the hippocampus and prefrontal cortex of HHcy rats, whereas EGb761 recovered the tau phosphorylation at those sites. Behavioral tests revealed that EGb761 rescued HHcy-induced spatial reference memory deficit and upregulated the expression of synapse-associated protein PSD95 and synapsin-1. EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.

Zeng K ，Li M ，Hu J ，Mahaman YAR ，Bao J ，Huang F ，Xia Y ，Liu X ，Wang Q ，Wang JZ ，Yang Y ，Liu R ，Wang X ... -  《-》

Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide-induced animal model of Alzheimer's disease.

Alpinae Oxyphyllae Fructus (AOF) with warming and tonifying the kidney and spleen, anti-salivation, anti-polyuria and anti-diarrhea functions is the dried ripe fruits of Alpinia oxyphylla Miq. (Zingiberaceae). As a traditional Chinese medicine, its application history is very long. The purpose of our study is to investigate the effects of different solvent extracts from AOF on lipopolysaccharide (LPS)-induced animal model of Alzheimer's disease (AD) to elucidate the traditional medical theories with modern pharmacological methods and provide a reference for further clarifying its active components and mechanisms. The method of stepwise screening was adopted in this paper. The animals were divided into 9 groups, including control (CT) group, model (MD) group, donepezil (DPZ) group, total extract (TT) group, petroleum ether extract (PE) group, chloroform extract (CF) group, ethyl acetate extract (EA) group, n-butanol extract (NB) group and water extract (WT) group. The anti-amnesic effects of different solvent extracts from AOF were measured in LPS-induced memory deficits mice by Y maze test and Morris water maze (MWM) test. Hematoxylin eosin (HE) staining was applied to observe pathological changes in hippocampus and cerebral cortex tissue of different groups. Biochemical indicators including ionized calcium-binding adaptor molecule 1 (IBA-1), interleukin beta 1 (IL-1β), Aβ1-42 and hyperphosphorylated tau proteins (p-tau) in hippocampus and cortex after treatment with LPS were measured according to the manufacturer's instructions of ELISA kits. HPLC was used to evaluate the major components of different extracts. It was found that successive intragastric administration of AOF (360 mg/kg) extracts for 14 days showed different degrees of improvement on LPS-induced AD model as measured by Y-maze test, Morris water maze test, and Histopathological examination. Moreover, the results of ELISA suggested petroleum ether (PE) extracts were worth recommending for inhibiting the high level of IBA-1, IL-1β, Aβ1-42 and p-tau in hippocampus and cortex after treatment with LPS. The present study demonstrated for the first time that AOF attenuated LPS-induced learning and memory impairment, which may be associated with its inhibitory effect on neuroinflammation, amyloids-β (Aβ) deposition and p-tau. This research provided a theoretical basis for elucidating the traditional theory of AOF, and was also the stepping stone to the next step.

Wang Y ，Wang M ，Fan K ，Li T ，Yan T ，Wu B ，Bi K ，Jia Y ... -  《-》