Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

A method for simultaneously identifying antioxidative compounds was developed using time-based LC-MS coupled with DPPH assay regardless of the time consuming process. The methanolic extract of Polygonum aviculare (Polygonaceae) showed significant DPPH radical scavenging activity. Time-based DPPH assay for simultaneous identification of active compounds from the extracts of P. aviculare was used. Major peaks of ethyl acetate fraction of P. aviculare showed high DPPH radical scavenging activity. A simple phenolic compound (1) and six flavonoids (2-7) were isolated from the ethyl acetate fraction of P. aviculare by silica gel and sephadex LH-20 column chromatography. The structures of seven compounds were determined to be protocatechuic acid (1), catechin (2), myricitrin (3), epicatechin-3-O-gallate (4), avicularin (5), quercitrin (6), and juglanin (7) based on the analysis of the 1H-NMR, 13C-NMR and ESI-MS data. All compounds exhibited significant antioxidant activity on DPPH assay and active compounds were well correlated with predicted one.
Catechin ; Chromatography ; Flavonoids ; Methanol ; Phenol ; Polygonum* ; Silica Gel

Methamphetamine (MA) is one of the most commonly abused drugs in the world by illegal drug users. Addiction to MA is a serious public health problem and effective therapies do not exist to date. It has also been reported that behavior induced by psychostimulants such as MA is related to histone deacetylase (HDAC). MeBib is an HDAC6 inhibitor derived from a benzimidazole scaffold. Many benzimidazole-containing compounds exhibit a wide range of pharmacological activity. In this study, we investigated whether HDAC6 inhibitor MeBib modulates the behavioral response in MA self-administered rats. Our results demonstrated that the number of active lever presses in MA self-administered rats was reduced by pretreatment with MeBib. In the hippocampus of rats, we also found MA administration promotes GluN2B, an NMDA receptor subunit, expression, which results in sequential activation of ERK/CREB/BDNF pathway, however, MeBib abrogated it. Collectively, we suggest that MeBib prevents the MA seeking response induced by MA administration and therefore, represents a potent candidate as an MA addiction inhibitor.

Non-alcoholic fatty liver disease (NAFLD) has the potential to develop into hepatic steatosis and progress to terminal liver diseases such as cirrhosis and hepatocellular carcinoma. This human clinical study was aimed to demonstrate that SPB-201 (powdered-water extract of Artemisia annua) can improve liver function in subjects with non-alcoholic liver dysfunction at mild to moderate levels. A decrease of 271% in aspartate aminotransferase (AST) level and a significant decrease of 334% in alanine aminotransferase (ALT) level was observed in the test group as compared to the control group at the 4 weeks follow-up. In addition, after 8 weeks, decreases of 199% in AST level and 216% in ALT level were reported in the test group as compared to the control group. These results confirmed that SPB-201 intake significantly enhanced liver function and health. Moreover, the Multidimensional Fatigue Scale score of the test group decreased but that of the control group increased, implicating that SPB-201 also eliminated overall fatigue. No significant adverse events were observed among all subjects during the study. Taken together, our clinical study confirmed the excellent efficacy and safety of SPB-201 in liver function improvement, showing the possibility of SPB-201 as a functional food to restore liver dysfunction and treat liver diseases.

Non-alcoholic fatty liver disease (NAFLD) has the potential to develop into hepatic steatosis and progress to terminal liver diseases such as cirrhosis and hepatocellular carcinoma. This human clinical study was aimed to demonstrate that SPB-201 (powdered-water extract of Artemisia annua) can improve liver function in subjects with non-alcoholic liver dysfunction at mild to moderate levels. A decrease of 271% in aspartate aminotransferase (AST) level and a significant decrease of 334% in alanine aminotransferase (ALT) level was observed in the test group as compared to the control group at the 4 weeks follow-up. In addition, after 8 weeks, decreases of 199% in AST level and 216% in ALT level were reported in the test group as compared to the control group. These results confirmed that SPB-201 intake significantly enhanced liver function and health. Moreover, the Multidimensional Fatigue Scale score of the test group decreased but that of the control group increased, implicating that SPB-201 also eliminated overall fatigue. No significant adverse events were observed among all subjects during the study. Taken together, our clinical study confirmed the excellent efficacy and safety of SPB-201 in liver function improvement, showing the possibility of SPB-201 as a functional food to restore liver dysfunction and treat liver diseases.

We investigated associations between breastfeeding duration and number of children breastfed and type 2 diabetes mellitus (T2DM) and glycemic control among parous women. We performed a cross-sectional analysis of data for 9,960 parous women from the Korea National Health and Nutritional Examination Survey (2010 to 2013). Having ever breastfed was inversely associated with prevalent T2DM (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.42 to 0.87). All ranges of total and average breastfeeding duration showed inverse associations with T2DM. Even short periods of breastfeeding were inversely associated with T2DM (adjusted OR, 0.61; 95% CI, 0.38 to 0.99 for a total breastfeeding duration ≤12 months; adjusted OR, 0.65; 95% CI, 0.42 to 0.99 for an average breastfeeding duration per child ≤6 months). A longer duration of breastfeeding was associated with better glycemic control in parous women with T2DM (P trend=0.004 for total breastfeeding duration; P trend <0.001 for average breastfeeding duration per child). Breastfeeding may be associated with a lower risk of T2DM and good glycemic control in parous women with T2DM. Breastfeeding may be a feasible method to prevent T2DM and improve glycemic control.
Blood Glucose ; Breast Feeding ; Child ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Female ; Humans ; Korea ; Lactation ; Methods ; Odds Ratio

Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.

Background: Evidence regarding the association between variabilities in obesity measures and health outcomes is limited. We aimed to examine the association between variabilities in obesity measures and cardiovascular outcomes and all-cause mortality. Methods: We identified 4,244,460 individuals who underwent health examination conducted by the Korean National Health Insurance Service during 2012, with ≥3 anthropometric measurements between 2009 and 2012. Variabilities in body weight (BW) and waist circumference (WC) were assessed using four indices including variability independent of the mean (VIM). We performed multivariable Cox proportional hazards regression analyses. Results: During follow-up of 4.4 years, 16,095, 18,957, and 30,200 cases of myocardial infarction (MI), stroke, and all-cause mortality were recorded. Compared to individuals with the lowest quartiles, incrementally higher risks of study outcomes and those of stroke and all-cause mortality were observed among individuals in higher quartiles of VIM for BW and VIM for WC, respectively. The multivariable adjusted hazard ratios and 95% confidence intervals comparing the highest versus lowest quartile groups of VIM for BW were 1.17 (1.12 to 1.22) for MI, 1.20 (1.16 to 1.25) for stroke, and 1.66 (1.60 to 1.71) for all-cause mortality; 1.07 (1.03 to 1.12) for stroke and 1.29 (1.25 to 1.33) for all-cause mortality regarding VIM for WC. These associations were similar with respect to the other indices for variability. Conclusion This study revealed positive associations between variabilities in BW and WC and cardiovascular outcomes and allcause mortality. Our findings suggest that variabilities in obesity measures are associated with adverse health outcomes in the general population.