Therapeutic potential of ginsenoside Rg3 and Rf for Huntington's disease.

Ginseng is a popular herbal medicine and known to have protective and therapeutic effects in various diseases. Ginsenosides are active gradients representing the diverse pharmacological efficacy of ginseng. Huntington's disease (HD) is incurable genetic disorder associated with mutant huntingtin (mHtt) aggregation in the central nervous system. This study was conducted to investigate the effects of ginsenoside Rg3 and Rf on mHtt aggregation, cell viability, mitochondrial function, and apoptotic molecules on HD model. To investigate the effect of ginsenosides on HD, neural stem cells were isolated from the R6/2 mouse brain and used as a cellular model of HD. Nuclear aggregation of mHtt was measured by immunocytochemistry, and expressions of mitochondrial biogenesis and apoptotic molecules were investigated by western blot. As a result, the number of mHtt aggregates positive cells has decreased by ginsenoside Rg3 and Rf treatment in cellular model of HD. Mitochondrial biogenesis-related molecules such as PGC-1α and phosphorylated CREB were increased or showed increased tendency by ginsenoside Rg3 and Rf. Apoptotic molecules, p53, Bax, and cleaved caspase-3, were down-regulated by treatment of ginsenoside Rg3 and Rf. In addition, Lysotracker staining result showed that cellular lysosomal content was reduced by ginsenoside Rg3 and Rf. Given that ginsenoside Rg3 and Rf have the potential to reduce mHtt aggregation and cellular apoptosis, these ginsenosides can be possible therapeutic candidates for treating HD phenotypes.

Electroacupuncture at the Zusanli and Baihui acupoints ameliorates type-2 diabetes-induced reductions in proliferating cells and differentiated neuroblasts in the hippocampal dentate gyrus with increasing brain-derived neurotrophic factor levels.

In the current study, we investigated whether electroacupuncture (EA) can inhibit pathological reductions in neurogenesis. Zucker diabetic fatty (ZDF) rats at 7 weeks of age were anesthetized with zoletil, and sham-acupuncture or EA at the Zusanli (ST36) and Baihui (GV20) acupoints was administered once a day for 5 weeks. In the ZDF group that received sham-EA (ZDF-Sham group), the blood glucose level was significantly increased together with age as compared to the control littermates [Zucker lean control (ZLC) rat]. In contrast, proliferating cells and differentiated neuroblasts were significantly decreased in the ZDF-Sham group compared to the ZLC group. Although EA treatment decreased blood glucose levels, this was not statistically significant when compared to blood glucose levels changes in the ZDF-Sham group. However, proliferating cells and differentiated neuroblasts were significantly increased with EA in ZDF rats as compared to those in the ZDF-Sham group. Brain-derived neurotrophic factor (BDNF) levels were significantly decreased in hippocampal homogenates of ZDF-Sham group compared to those in the ZLC group. The EA treatment significantly increased the BDNF levels compared to those in the ZDF-Sham group, and BDNF levels in this group were similar to those in the ZLC group. These results suggest that EA at ST36 and GV20 can ameliorate the reductions in proliferating cells and differentiated neuroblasts in the dentate gyrus induced by type-2 diabetes without significantly reducing blood glucose levels with increasing BDNF levels.

Electroacupuncture enhances motor recovery performance with brain-derived neurotrophic factor expression in rats with cerebral infarction.

OBJECTIVE: Electroacupuncture (EA) is a traditional medicine in patients with post-stroke rehabilitation. Brain-derived neurotrophic factor (BDNF) is a potent growth factor involved in recovery following cerebral injury. The aim of the present study was to investigate whether EA increases BDNF levels and facilitates functional recovery. METHODS: Occlusion of the middle cerebral artery was performed in rats (N=12) followed by reperfusion. EA was applied at the GV20 (Baihui) acupoint. Motor and sensory functions were monitored on the Garcia scale for 2 weeks. Expressions of BDNF and receptor tyrosine kinase B (trkB) were determined by immunoblotting and immunohistochemistry. RESULTS: Improvement of Garcia scores, particularly in motor performance, were noted in the group with EA stimulation (p<0.05). With EA application, BDNF was elevated in the ischaemic hemisphere with increased numbers of BDNF(+) cells. Increased expression of trkB was also detected. CONCLUSION: These results indicate that EA at GV20 improves motor recovery and stimulates BDNF/trkB expression in rats with cerebral ischaemia.

Cytokine reporter mouse system for screening novel IL12/23 p40-inducing compounds.

Cytokines interleukin (IL) 12 and 23 play critical roles in linking innate and adaptive immune responses. They are members of heterodimeric cytokines, sharing a subunit p40. Although IL12/23 p40 is mainly induced in macrophages and dendritic cells (DCs) after stimulation with microbial Toll-like receptor ligands, methods to monitor the cells that produce IL12/23 p40 in vivo are limited. Recently, the mouse model to track p40-expressing cells with fluorescent reporter, yellow fluorescent protein, has been developed. Macrophages and DCs from these mice faithfully reported p40 induction using the fluorescent marker. Here we took advantage of these reporter mice to screen bio-compounds for p40-inducing activity. After screening hundreds of compounds, we found several extracts inducing IL12/23 p40 gene expression. Treatment of DCs with these extracts induced the expression of MHC class II and co-stimulatory molecules, which implies that these might be useful as adjuvants. Next, the in vivo target immune cells of candidate compounds were examined. The reporter system can be useful to identify cells producing IL12 or IL23 in vivo as well as in vitro. Thus, our cytokine reporter system proved to be a valuable reagent for screening for immunostimulatory molecules and identification of target cells in vivo.