Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia.

OBJECTIVE: To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD). METHODS: A rat model of VD was induced by bilateral common carotid arteries occlusion (BCCAO). Low-dose or high-dose PF (20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (rCBV), regional cerebral blood flflow (rCBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. mRNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation. RESULTS: The behavioral analysis showed that PF could decrease the escape latency time (P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P<0.05). Likewise, PF remarkably promoted the rCBV (P<0.05), rCBF and decreased per minute MTT (P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1ß, IL-6 and TNF-α as well as inhibited the mRNA expression of IL-1ß, IL-6 and TNF-α in the hippocampus of VD rats (P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats (P<0.05 or P<0.01). In addition, PF signifificantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats. CONCLUSIONS: PF signifificantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflflammatory response in VD rats. In addition, the anti-inflflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.

Paeoniflorin attenuates hippocampal damage in a rat model of vascular dementia.

Paeoniflorn (PF), the principal bioactive component of Paeoniae radix prescribed in traditional Chinese medicine, possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. Previous studies have demonstrated that PF significantly attenuates memory impairment in rats with vascular dementia (VD). In the present study, a bilateral common carotid artery occlusion (BCCAO) rat model was used to explore the underlying mechanisms of PF. The expression levels of neuron-specific enolase (NSE), S100ß, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, cytochrome c and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured by western blot analysis. The results showed that administration of PF for 28 days significantly decreased the expression levels of NSE and S100ß, both sensitive markers for brain damage, in vascular dementia (VD) model rats. In addition, PF inhibited the initiation of apoptotic cell death and attenuated the decreased expression levels of BDNF induced by bilateral common carotid artery occlusion. These data confirm the neuroprotective effects of PF on VD and provide a novel insight into the long-term use of PF as a potential treatment in the stages of early cognitive impairment in VD.

Nerve growth factor promotes human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa.

Nerve growth factor (NGF) was first found in the central nervous system and is now well known for its multiple pivotal roles in the nervous system and immune system. However, more and more evidences showed that NGF and its receptors TrkA and p75 were also found in the head and tail of spermatozoa, which indicate the possible effect of NGF on the sperm motility. Nevertheless, the exact role of NGF in the human sperm motility remains unclear until now. In this study, we investigated the effect of NGF on human sperm motility, and the results showed that NGF could promote human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa. Further analysis demonstrated that NGF promoted the sperm motility in a dose-dependent manner in vitro. These results may facilitate the further studies on human fertility and assisted reproduction techniques.

Effect of daily milk supplementation on serum and umbilical cord blood folic acid concentrations in pregnant Han and Mongolian women and birth characteristics in China.

Many studies have demonstrated the efficacy of folic acid (FA) supplementation in prevention of neural tube defects (NTDs), although the extent of NTDs varies among individuals of different races and ethnic origin. China is a multi-ethnic country with no standard practice for FA-fortified food. Milk is consumed by women, but little is known about the effects of milk on folate concentration in maternal blood and neonatal umbilical cord blood in Han and Mongolian women after stopping taking the supplement for a month and five month, respectively. The objective of this study was to determine whether only daily consumption of liquid milk can increase the blood folate concentration in pregnant women and whether there are differences in blood folate concentrations between Han and Mongolian women after cessation of FA supplementation. Of the 4052 women enrolled in the parallel group design study. Three thousand five hundred and twenty-six women had confirmed pregnancies and were randomized to receive liquid milk or not until delivery. Women who consumed the liquid milk had significantly increased serum folate concentrations at 16 and 32 weeks of gestation as well as cord blood at birth compared to control groups in both ethnic groups. Infants born to women drinking milk also had better the term birth weight and height, which may be related to the increased concentration of folate. In conclusion, daily consumption of milk can increase the serum folate concentration in pregnant Han and Mongolian women in China (differences in the efficacy of FA and milk supplementation) and may enhance birth outcomes.

Tanshinol protects hippocampus and attenuates vascular dementia development.

Tanshinol (3-(3',4'-dihydroxyphenyl)-(2R)-lactic acid, TSL) is widely used in traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases. Here, we assessed whether TSL protected hippocampus and attenuated vascular dementia (VD) development in rats. The behavioral analysis showed that TSL could decrease the distance and latency time, and increase the swim speed in water maze in rats subjected to VD. TSL remarkably increased acetylcholine level and decreased acetylcholinesterase activity in rats subjected to VD. Likewise, TSL remarkably decreased malondialdehyde and increased superoxide dismutase levels in rats subjected to VD. Furthermore, treatment with TSL reduced the level of dead neurons in dentate gyrus. In addition, TSL upregulated growth-associated protein 43 (GAP43) and vascular endothelial growth factor (VEGF) expression and downregulated phosphorylated Akt (p-AKt) and phosphorylated glycogen synthase kinase (p-GSK3ß) expression in hippocampus in rats subjected to VD. These results suggest that TSL may be a potential compound in VD model.

Tetramethylpyrazine attenuates atherosclerosis development and protects endothelial cells from ox-LDL.

PURPOSE: We assessed whether tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii Franchat, attenuates atherosclerosis (AS) development in rabbits and protects endothelial cells injured by ox-LDL. METHODS: In vivo, rabbits subjected to atherosclerosis were treated with TMP (75 and 150 mg/kg) by oral gavage for 12 weeks. In vitro, rat aortic endothelial cells (RAECs) were stimulated by ox-LDL. RESULTS: TMP treatment with 75 and 150 mg/kg significantly reduced the relative atherosclerosis area ratio in the aorta (0.41 ± 0.042, 0.27 ± 0.047 vs. 0.66 ± 0.058 in AS), the ratio of intimal/medial thickness (0.54 ± 0.09, 0.39 ± 0.07 vs. 1.1 ± 0.3 in AS) and the number of monocytes in intimal (10.1 ± 2.8, 8.2 ± 2.0 vs. 14.1 ± 4.9 counts/mm(2) in AS). TMP also decreased levels of TC (15 ± 4.2 to 6.1 ± 1.2 mmol/L), TG (1.8 ± 0.3 to 1.08 ± 0.24 mmol/L), LDL-C (20.1 ± 4.3 to 10.2 ± 1.6 mmol/L) and increased HDL-C levels (0.40 ± 0.08 to 0.85 ± 0.17 mmol/L) in atherosclerosis rabbit plasma. TMP decreased the MCP-1 (187.3 ± 38.4 to 86.1 ± 17.2 pg/ml) and ICAM-1 (350.6 ± 43.7 to 260.6 ± 46.1 pg/ml) levels in plasma and inhibited LOX-1 expression in the rabbit aortas. Moreover, our in vitro study revealed that TMP suppressed monocyte adhesion to RAECs, inhibited RAEC migration, and down-regulated MCP-1 and ICAM-1 expression in ox-LDL-injured RAECs. Likewise, TMP inhibited LOX-1 and 5-LOX expression, and prevented nuclear accumulation of RelA/p65 and IκB degradation in ox-LDL-injured RAECs. Furthermore, TMP suppressed ox-LDL-induced activations of p-ERK, p-p38, and p-JNK MAPK. CONCLUSION: TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.

Intranasal administration of nerve growth factor produces antidepressant-like effects in animals.

Many works showed that nerve growth factor (NGF) injected into the brain of animal model emerges potential antidepressant effects. However, this route of administration significantly restricts the application of NGF clinically. Here, we reported that intranasal NGF could provide an alternative to intraventricular injection. The behavioral analysis showed that intranasal administration of NGF reduced the immobility time in forced swimming test (FST) and tail suspension test (TST) in mice. Likewise, intranasal NGF increased the sucrose intake and the locomotor activity in rats after unpredictable chronic mild stress (UCMS). Furthermore, intranasal NGF increased the levels of monoamine neurotransmitters (norepinephrine, dopamine) in the frontal cortex and hippocampus and affected the number of 5-bromodeoxyuridine (BrdU), c-fos and caspase-3 positive neurons in dentate gyrus of hippocampus in rats after UCMS. In summary, intranasal NGF had significant antidepressant effects on animal models of depression and this route of administration may provide a promising way to deliver NGF to brain in a therapeutic perspective.