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 ... -  《-》

S-propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuates lipopolysaccharide-induced spatial learning and memory impairment: involvement of TNF signaling and NF-κB pathway in rats.

Neuroinflammation exacerbates hyperphosphorylated tau and amyloid-β (Aβ) generation by generating a plethora of inflammatory mediators and neurotoxic compounds in a transgenic model of Alzheimer's disease (AD), and it was reported that hydrogen sulfide (H₂S) attenuates lipopolysaccharide (LPS)-induced neuroinflammation both in vitro and in vivo. In the present study, the protective effects of S-propargyl-cysteine (SPRC) on spatial learning and memory impairment induced by LPS were examined in vivo, and the possible mechanisms were explored. The data showed that SPRC administration by intraperitoneal (i.p.) injection may attenuate cognitive impairment induced by bilateral intracerebroventricular (b.i.c.v.) injection of 5 μg of LPS in rats. Subsequently, SPRC prevented a decrease of H₂S levels in rat hippocampus subjected to LPS. Furthermore, SPRC afforded beneficial actions in inhibitions tumor necrosis factor (TNF)-α, TNF-α receptor 1 (TNFR1) and Aβ generation, as well as IκB-α degradation and phospho-transcription factors of the nuclear factor κB p65 (p-NF-κB p65) activation induced by LPS. These findings suggested that SPRC, a novel H₂S-modulated agent, might be a potential agent for the treatment of neuroinflammation-related diseases, such as AD.

Gong QH ，Wang Q ，Pan LL ，Liu XH ，Xin H ，Zhu YZ ... -  《-》

Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model.

Lee KM ，Jeon SM ，Cho HJ 《-》

Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells.

Chen TH ，Kao YC ，Chen BC ，Chen CH ，Chan P ，Lee HM ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》

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 ... -  《-》