Eleutheroside B or E enhances learning and memory in experimentally aged rats

Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer＇s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E （50, 100, 200 mg/kg）, and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.

Neuroprotective effect of Eleutheroside B on 1-methyl-4-phenylpyridinium ion-induced apoptosis in PC12 cells

Apoptosis and viability of PC12 cells following 1-methyl-4-phenylpyridinium ion （MPP＋）-induced injury were monitored by flow cytometry, following Annexin V-propidium iodide double labeling, and 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay, respectively. The release of lactate dehydrogenase, superoxide dismutase activity and levels of malondialdehyde were determined by UV spectrophotometry. The changes in mitochondrial membrane potential and the intracellular concentration of calcium were determined by flow cytometry, and the activity of caspase-3 was monitored by western blot. According to cell viability and apoptosis studies, MPP＋-induced apoptosis in PC12 cells was inhibited in the presence of 10 tJg/mL of Eleutheroside B Our results indicate that the neuroprotective effect of Eleutheroside B, following MPP＋-induced apoptosis in PC12 cells, involves increasing the anti-oxidative stress capacity of cells, maintaining the high-energy state of mitochondrial membrane potential, reducing intracellular calcium concentration and inhibiting caspase-3 activity.

Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model

Objective To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide(LPS)-induced depression mice model.Methods Depression mice model was established by lipopolysaccharide(LPS)injection.Totally 48 mice were randomly divided into 6 groups(8 rats per group)according to a random number table,including normal,model,fluoxetine(20 mg/kg),geniposide(100 mg/kg)+eleutheroside B(100 mg/kg),geniposide+eleutheroside B+WAY 100635(0.03 mg/kg),geniposide+eleutheroside B+N-methyl-D-aspartic acid receptor(NMDA,75 mg/kg)groups,respectively.After continuous administration for 10 days,autonomic activity tests after 30 min of administration were performed on the 10th day.On the 11th day,except for the normal group,the mice in the other groups were intraperitoneally injected with LPS(1 mg/kg),and the behavioral tests were performed 4 h later.Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)levels in mice serum.The mRNA expression of indoleamine 2,3-dioxygenase(IDO)and nuclear transcription factor(NF-κB)were detected by real-time quantitative polymerase chain reaction.Western-blot analysis was used to detect IDO and NF-κB protein expressions in hippocampus tissue.Results Compared with the normal group,a single administration of LPS increased the immobility time in the forced swimming test(FST)and tail suspension test(TST,P<0.01),without affecting autonomous activity.Compared with the model group,fluoxetine and geniposide+eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST,decreased serum IL-1βcontent,inhibited the expression levels of NF-κB gene and protein in hippocampus tissues(P<0.05 or P<0.01).Compared with the model group,geniposide+eleutheroside B treatment significantly reduced serum TNF-αcontent and inhibited IDO mRNA and protein expressions in hippocampus(P<0.05 or P<0.01).In addition,NMDA partly prevented the inhibition of IDO mRNA expression by geniposide+eleutheroside B;NMDA and WAY-100635 also partly prevented the reduction of IL-1ßcontent induced by geniposide+eleutheroside B treatment(P<0.05 or P<0.01).Conclusions The combination of geniposide and eleutheroside B showed a certain antidepression-like effect.Its main mechanism of action may be contributed to inhibiting the activation of NF-κB,decreasing the proinflammatory cytokines such as TNF-α,IL-1β,and inhibiting in the neuroinflammatory reaction.Additionally,it also affects tryptophan metabolism,reduces the expression of a key enzyme of tryptophan metabolism,IDO.And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.