Ginsenoside Re protects against phencyclidine-induced behavioral changes and mitochondrial dysfunction via interactive modulation of glutathione peroxidase-1 and NADPH oxidase in the dorsolateral cortex of mice.

We investigated whether ginsenoside Re (Re) modulates phencyclidine (PCP)-induced sociability deficits and recognition memory impairments to extend our recent finding. We examined the role of GPx-1 gene in the pharmacological activity of Re against mitochondrial dysfunction induced by PCP in the dorsolateral cortex of mice. Since mitochondrial oxidative stress activates NADPH oxidase (PHOX), we applied PHOX inhibitor apocynin for evaluating interactive modulation between GPx-1 and PHOX against PCP neurotoxicity. Sociability deficits and recognition memory impairments induced by PCP were more pronounced in GPx-1 knockout (KO) than in wild type (WT) mice. PCP-induced mitochondrial oxidative stress, mitochondrial dysfunction, and membrane translocation of p47phox were more evident in GPx-1 KO than in WT. Re treatment significantly attenuated PCP-induced neurotoxic changes. Re also significantly attenuated PCP-induced sociability deficits and recognition memory impairments. The attenuation by Re was comparable to that by apocynin. The attenuation was more obvious in GPx-1 KO than in WT. Importantly, apocynin did not show any additional positive effects on the neuroprotective activity of Re, indicating that PHOX is a molecular target for therapeutic activity of Re. Our results suggest that Re requires interactive modulation between GPx activity and PHOX (p47phox) to exhibit neuroprotective potentials against PCP insult.

Ginsenoside Re Protects Trimethyltin-Induced Neurotoxicity via Activation of IL-6-Mediated Phosphoinositol 3-Kinase/Akt Signaling in Mice.

Ginseng (Panax ginseng), an herbal medicine, has been used to prevent neurodegenerative disorders. Ginsenosides (e.g., Re, Rb1, or Rg1) were obtained from Korean mountain cultivated ginseng. The anticonvulsant activity of ginsenoside Re (20 mg/kg/day × 3) against trimethyltin (TMT) insult was the most pronounced out of ginsenosides (e.g., Re, Rb1, and Rg1). Re itself did not significantly alter tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-ϒ), and interleukin-1ß (IL-1ß) expression, however, it significantly increases the interleukin-6 (IL-6) expression. In addition, Re attenuated the TMT-induced decreases in IL-6 protein level. Therefore, IL-6 knockout (-/-) mice were employed to investigate whether Re requires IL-6-dependent neuroprotective activity against TMT toxicity. Re significantly attenuated TMT-induced lipid peroxidation, protein peroxidation, and reactive oxygen species in the hippocampus. Re-mediated antioxidant effects were more pronounced in IL-6 (-/-) mice than in WT mice. Consistently, TMT-induced increase in c-Fos-immunoreactivity (c-Fos-IR), TUNEL-positive cells, and nuclear chromatin clumping in the dentate gyrus of the hippocampus were significantly attenuated by Re. Furthermore, Re attenuated TMT-induced proapoptotic changes. Protective potentials by Re were comparable to those by recombinant IL-6 protein (rIL-6) against TMT-insult in IL-6 (-/-) mice. Moreover, treatment with a phosphoinositol 3-kinase (PI3K) inhibitor, LY294002 (1.6 µg, i.c.v) counteracted the protective potential mediated by Re or rIL-6 against TMT insult. The results suggest that ginsenoside Re requires IL-6-dependent PI3K/Akt signaling for its protective potential against TMT-induced neurotoxicity.

Treatment with Mountain-Cultivated Ginseng Alleviates Trimethyltin-Induced Cognitive Impairments in Mice via IL-6-Dependent JAK2/STAT3/ERK Signaling.

Panax ginseng is the most widely used herbal medicine for improving cognitive functions. The pharmacological activity and underlying mechanisms of mountain-cultivated ginseng, however, have yet to be clearly elucidated, in particular, against trimethyltin-induced cognitive dysfunction. We previously reported that interleukin-6 plays a protective role against trimethyltin-induced cognitive dysfunction. Because of this, we have implemented a study system that uses interleukin-6 null (-/-) and wild-type mice. Interestingly, mountain-cultivated ginseng significantly upregulated interleukin-6 expression. With this study, we sought to determine whether the interleukin-6-dependent modulation of the Janus kinase 2/signal transducer activator of transcription 3 and extracellular signal-regulated kinase signaling network is also associated with the pharmacological activity of mountain-cultivated ginseng against trimethyltin-induced cognitive dysfunction. Trimethyltin treatment (2.4 mg/kg, intraperitoneal) causes the downregulation of Janus kinase 2/signal transducer activator of transcription 3, extracellular signal-regulated kinase signaling, and impairment of the cholinergic system. We found that mountain-cultivated ginseng treatment (50 mg/kg, intraperitoneal) significantly attenuated cognitive impairment normally induced by trimethyltin by upregulating p-Janus kinase 2/signal transducer activator of transcription 3, p-extracellular signal-regulated kinase signaling, and the cholinergic system. Trimethyltin-induced cognitive impairments were more pronounced in interleukin-6 (-/-) mice than wild-type mice, and they were markedly reduced by treatment with either mountain-cultivated ginseng or recombinant interleukin-6 protein (6 ng, intracerebroventricular). Additionally, treatment with either AG490 (20 mg/kg, intraperitoneal), a Janus kinase 2/signal transducer activator of transcription 3 inhibitor, or U0126 (2 µg/head, intracerebroventricular), an extracellular signal-regulated kinase inhibitor, reversed the effects of mountain-cultivated ginseng treatment. The effects of mountain-cultivated ginseng treatment were comparable to those of recombinant interleukin-6 protein in interleukin-6 (-/-) mice. Our results, therefore, suggest that mountain-cultivated ginseng acts through interleukin-6-dependent activation of Janus kinase 2/signal transducer activator of transcription 3/extracellular signal-regulated kinase signaling in order to reverse cognitive impairment caused by trimethyltin treatment.

Effects of vitamin D on blood pressure in patients with type 2 diabetes mellitus.

PURPOSE: Previous studies have suggested that vitamin D supplementation may decrease blood pressure in patients with type 2 diabetes, although conflicting results have been reported. The purpose of this meta-analysis was to evaluate the effects of the vitamin D supplementation on blood pressure in patients with type 2 diabetes. METHODS: A meta-analysis of published randomized controlled trials was conducted. Eligible studies were identified via a literature search of the MEDLINE (PubMed), EMBASE, and Cochrane Library databases through to May 25, 2015. The endpoint of the analysis was the change in blood pressure due to vitamin D treatment in patients with type 2 diabetes. These changes were calculated as the difference between the baseline and final measurements performed in each study. A fixed-effects model was used to calculate the combined effect estimates; in the presence of heterogeneity, a random-effects model was used. RESULTS: A total of 15 articles were included in the meta-analysis. All 15 articles, including 1,134 patients with type 2 diabetes, were analyzed for systolic blood pressure (SBP), and 13 articles, including 793 patients, were analyzed for diastolic blood pressure (DBP). The combined-effect estimate of vitamin D intervention on SBP was -0.121 mmHg (95% confidence interval (CI) -0.355 to 0.113, p = 0.311), and considerable heterogeneity was observed between studies (p < 0.001, I(2)= 74.2%). For DBP, the combined effect estimate was -0.160 mmHg (95% CI -0.298 to -0.022, p = 0.023), and no heterigenieity was observed (p = 0.673, I(2) = 0.0%). CONCLUSIONS: This study is the first meta-analysis of the effect of vitamin D supplementation on blood pressure in patients with type 2 diabetes. This meta-analysis demonstrated that vitamin D supplementation may result in a reduction in DBP in patients with type 2 diabetes. However, additional studies with large sample sizes and longer durations are needed to establish a relationship between vitamin D and blood pressure in patients with type 2 diabetes.

Beneficial Effects of Red Yeast Rice on High-Fat Diet-Induced Obesity, Hyperlipidemia, and Fatty Liver in Mice.

Obesity is a common cause of hyperlipidemia, which is a major coronary risk factor. Previous studies have shown red yeast rice (RYR) effectiveness in lowering low-density lipoprotein cholesterol. The aim of this study was to investigate the effects of RYR on obesity and hyperlipidemia. Mice were randomly separated into five groups: the control group with a normal diet, the high-fat diet (HFD) group fed a HFD without any treatment, and HFD-fed groups supplemented with RYR (1 g/kg/day for 8 weeks, 1 g/kg/day for 12 weeks, and 2.5 g/kg/day for 8 weeks). Body weight was recorded twice and food intake thrice weekly. Liver and fat pads were surgically removed and weighed. The levels of lipid parameters, liver enzymes, and leptin levels were measured. The HFD feeding resulted in obesity, which was associated with increases in body weight, liver weight, fat pad weight, liver enzymes, and plasma leptin levels with the development of hyperlipidemia. RYR prevented weight gain and fat pad weight in mice fed a HFD. RYR alleviated blood lipid parameters, liver enzymes, and leptin levels, and improved atherogenic index. These findings suggest that RYR has therapeutic potential in treating obesity and hyperlipidemia.

Clinical effect of a polysaccharide-rich extract of Acanthopanax senticosus on alcohol hangover.

The present study aimed to examine the effects polysaccharide-rich extract of Acanthopanax senticosus (PEA) on blood alcohol concentration (BAC) and hangover as well as blood lab parameters. A randomized, placebo-controlled, double-blind crossover trial was conducted. The PEA was orally administered before and after consuming alcohol 1.75 g/kg of pure alcohol. After alcohol consumption, BAC was measured for evaluation of alcohol pharmacokinetics. In the second day morning, subjects were asked to complete the Acute Hangover Scale (AHS) questionnarie. BAC results showed little difference between placebo and PEA groups, indicating that PEA does not have an effect on the pharmacokinetics of alcohol. However, several AHS items (i.e., tired, headache, dizziness, stomachache and nausea) and AHS total score were significantly improved by PEA. Blood lab parameters were significantly altered by alcohol in the placebo group. The alteration by alcohol of glucose and C-reactive protein (CRP) level was significantly attenuated by PEA. Therefore, PEA may have potential to reduce the severity of the alcohol hangover by inhibiting the alcohol-induced hypoglycemia and inflammatory response.