Chronic marijuana use moderates the correlations of serum cholesterol with systemic mitochondrial function and fluid cognition.

Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the latter is associated with mitochondrial function and fluid cognition. We recruited 19 chronic MJ users and 20 nonusers with matched age, BMI, sex, ethnicity, and education. We measured their fluid cognition, mitochondrial function (basal and max respiration, ATP production) in peripheral blood mononuclear cells, cholesterol content in serum lipoprotein fractions, enterolactone/creatinine ratio in urine as a marker for dietary polyphenol intake, and lipase activity in serum. We found that higher percentage of large HDL cholesterol (HDL-C) correlated positively, while that of small HDL-C correlated inversely, with mitochondrial function among MJ users, but correlations of the opposite directions were found among nonusers. The concentrations of large and intermediate HDL-C correlated positively with mitochondrial function and fluid cognition among MJ users, but not among nonusers. Both percentage and concentration of large HDL-C correlated positively, while those of small HDL-C correlated inversely, with amounts of daily and lifetime MJ use. In all participants, higher urinary enterolactone/creatinine ratio and lower serum lipase activity were associated with higher large HDL-C/small HDL-C ratio, implying greater RCT. This study suggests that high MJ use may compromise RCT, which is strongly associated with mitochondrial function and fluid cognition among MJ users.

Dysregulated bile acid signaling contributes to the neurological impairment in murine models of acute and chronic liver failure.

BACKGROUND: Hepatic encephalopathy (HE), a severe neuropsychiatric complication, is associated with increased blood levels of ammonia and bile acids (BAs). We sought to determine (1) whether abnormally increased blood BAs in liver cirrhotic patients with HE is caused by elevation of apical sodium-dependent BA transporter (ASBT)-mediated BA reabsorption; and (2) whether increased BA reabsorption would exacerbate ammonia-induced brain injuries. METHODS: We quantitatively measured blood BA and ammonia levels in liver cirrhosis patients with or without HE and healthy controls. We characterized ASBT expression, BA profiles, and ammonia concentrations in a chronic liver disease (CLD) mouse model induced by streptozotocin-high fat diet (STZ-HFD) and an azoxymethane (AOM) - induced acute liver failure (ALF) mouse model. These two mouse models were treated with SC-435 (ASBT inhibitor) and budesonide (ASBT activator), respectively. FINDINGS: Blood concentrations of ammonia and conjugated BAs were substantially increased in cirrhotic patients with HE (n = 75) compared to cirrhotic patients without HE (n = 126). Pharmacological inhibition of the enterohepatic BA circulation using a luminal- restricted ASBT inhibitor, SC-435, in mice with AOM-induced ALF and STZ-HFD -induced CLD effectively reduced BA and ammonia concentrations in the blood and brain, and alleviated liver and brain damages. Budesonide treatment induced liver and brain damages in normal mice, and exacerbated these damages in AOM-treated mice. INTERPRETATION: ASBT mediated BA reabsorption increases intestinal luminal pH and facilitates conversion of intestinal ammonium to ammonia, leading to abnormally high levels of neurotoxic ammonia and cytotoxic BAs in the blood and brain. Inhibition of intestinal ASBT with SC-435 can effectively remove neurotoxic BAs and ammonia from the bloodstream and thus, mitigate liver and brain injuries resulting from liver failure.

Food withdrawal alters the gut microbiota and metabolome in mice.

Food withdrawal as a health-enhancing measure has beneficial effects on aging, disease prevention, and treatment. However, the cellular and molecular mechanisms involving gut microbial changes and metabolic consequences resulting from food withdrawal have yet to be elucidated. In this study, we subjected lean and obese mice to a dietary intervention that consisted of a 4-d complete food withdrawal and an 8-d 50% food withdrawal, and we studied changes in cecal microbiome and host serum metabolome. The abundance of potentially pathogenic Proteobacteria was decreased and Akkermansia muciniphila was elevated by food withdrawal in mice fed a high-fat diet (HFD). Meanwhile, food withdrawal decreased the abundance of metabolites in branched chain amino acid, lipid, and free fatty acid metabolisms in host serum, more so in HFD mice than in normal mice. Microbial predicted function also showed that food withdrawal decreased the abundance of microbes associated with predicted diseases in the HFD group but not in the normal chow group. Correlation between the microbiome data and metabolomics data revealed a strong association between gut microbial and host metabolic changes in response to food withdrawal. In summary, our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes in gut microbiota, which were closely associated with the host metabolome.-Zheng, X., Zhou, K., Zhang, Y., Han, X., Zhao, A., Liu, J., Qu, C., Ge, K., Huang, F., Hernandez, B., Yu, H., Panee, J., Chen, T., Jia, W., Jia, W. Food withdrawal alters the gut microbiota and metabolome in mice.

Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users.

Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal microbiota in chronic MJ users. Nineteen chronic MJ users and 20 non-users were evaluated using the Cognition Battery in NIH Toolbox, their mt function for ATP production, and basal and maximal respirations were measured in PBMCs using the Seahorse XFe96 Analyzer, and the abundances of Prevotella and Bacteroides (associated with plant-based and animal product-based diet, respectively) were calculated from stool microbiota analysis. Average Prevotella:Bacteroides ratio was ~13-fold higher in nonusers than users. Lifetime MJ use correlated inversely with Prevotella:Bacteroides ratio (p = 0.05), mt function (p = 0.0027-0.0057), and Flanker Inhibitory Control and Attention (p = 0.041). Prevotella abundance correlated positively, while Bacteroides abundance correlated inversely, with mt function across all participants (p = 0.0004-0.06). Prevotella abundance also correlated positively with scores of Fluid Cognition, Flanker Inhibitory Control and Attention, List Sorting, and Dimension Change Card Sort in MJ users, but not in non-users (interaction-p = 0.018-0.05). Similarly, mt function correlated positively with scores of Fluid Cognition and Flanker Inhibitory Control and Attention in MJ users, but not in non-users (interaction-p = 0.0018-0.08). These preliminary findings suggest that MJ use is associated with alterations of gut microbiota and mt function, which may further contribute to cognitive deficits. We posited that MJ-associated low vegetable/fruit intake may contribute to these changes. Future studies are needed to delineate the relationships among diet, microbiota, mt function, and cognition in MJ users.

Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients.

The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry. A total of 140 metabolites were identified. Clear separations between each two groups were obtained using the partial least squares discriminate analysis of 9 lipid metabolites. Progressively lower levels of long-chain lysophosphatidylcholines (lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4) were observed from CHB to cirrhosis to carcinoma; lower levels of lysoPC a C20:4 were found in patients with higher model for end-stage liver disease in the same disease group; and lysoPC a C20:3 levels were lower in Child-Pugh Class C than in Class A and Class B in HBV-associated cirrhosis and HBV-associated HCC groups. The octadecadienyl carnitine level was higher in HBV-associated cirrhosis group than in other two groups. Serum levels of selected long-chain lysoPCs are promising markers for the progression of HBV-associated liver diseases.

Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity.

Endogenous fatty acid metabolism that results in elongation and desaturation lipid products is thought to play a role in the development of type 2 diabetes mellitus (T2DM). In this study, we evaluated the potential of estimated elongase and desaturase activities for use as predictive markers for T2DM remission after Roux-en-Y gastric bypass (RYGB). The results of a targeted metabolomics approach from 2 independent studies were used to calculate 24 serum FA concentration ratios (product/precursor). Gene expression data from an open public data set was also analyzed. In a longitudinal study of 38 obese diabetic patients with RYGB, we found higher baseline stearic acid/palmitic acid (S/P) ratio. This ratio reflects an elovl6-encoded elongase enzyme activity that has been found to be associated with greater possibility for diabetes remission after RYGB [odds ratio, 2.16 (95% CI 1.10-4.26)], after adjustment for age, gender, body mass index, diabetes duration, glycosylated hemoglobin A1c, and fasting C-peptide. Our results were validated by examination of postsurgical elovl6 gene expression in morbidly obese patients. The association of S/P with the metabolic status of obese individuals was further validated in a cross-sectional cohort of 381 participants. In summary, higher baseline S/P was associated with greater probability of diabetes remission after RYGB and may serve as a diagnostic marker in preoperative patient assessment. - Zhao, L., Ni, Y., Yu, H., Zhang, P., Zhao, A., Bao, Y., Liu, J., Chen, T., Xie, G., Panee, J., Chen, W., Rajani, C., Wei, R., Su, M., Jia, W., Jia, W. Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity.

Anti-inflammatory Function of Phyllostachys Edulis Extract in the Hippocampus of HIV-1 Transgenic Rats.

HIV induces neuroinflammation. We evaluated the anti-inflammatory effect of an extract from bamboo Phyllostachys edulis in the hippocampus of HIV-1 transgenic (TG) rats. Five (5) one-month-old TG rats and 5 Fisher 344 (F344) rats were fed a control diet, another 5 TG rats were fed the control diet supplemented with bamboo extract (BEX, 11 grams dry mass per 4057 Kcal). After 9 months of dietary treatment, the gene and protein expression of interleukin 1 beta (IL-1ß), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1), and the protein expression p65 and c-Jun were analyzed in the hippocampus. Compared to the F344 rats, the TG rats fed control diet showed significantly higher protein expression of GFAP and c-Jun, and mRNA and protein levels of IL-1ß. BEX supplement to the TG rats significantly lowered protein expressions of GFAP, p65, and c-Jun, and showed a trend to decrease the protein expression of IL-1ß. Compared to the TG rats, TG+BEX rats also downregulated the mRNA levels of IL-1ß and TNFα. In summary, neuroinflammation mediated by the NFκB and AP-1 pathways in the hippocampus of the TG rats was effectively abolished by dietary supplement of BEX.

Global and Targeted Metabolomics Evidence of the Protective Effect of Chinese Patent Medicine Jinkui Shenqi Pill on Adrenal Insufficiency after Acute Glucocorticoid Withdrawal in Rats.

Glucocorticoids are commonly used in anti-inflammatory and immunomodulatory therapies, but glucocorticoid withdrawal can result in life-threatening risk of adrenal insufficiency. Chinese patented pharmaceutical product Jinkui Shenqi pill (JKSQ) has potent efficacy on clinical adrenal insufficiency resulting from glucocorticoid withdrawal. However, the underlying molecular mechanism remains unclear. We used an animal model to study JKSQ-induced metabolic changes under adrenal insufficiency and healthy conditions. Sprague-Dawley rats were treated with hydrocortisone for 7 days with or without 15 days of JKSQ pretreatment. Sera were collected after 72 h hydrocortisone withdrawal and used for global and free fatty acids (FFAs)-targeted metabolomics analyses using gas chromatography/time-of-flight mass spectrometry and ultraperformance liquid chromatography/quadruple time-of-flight mass spectrometry. Rats without hydrocortisone treatment were used as controls. JKSQ pretreatment normalized the significant changes of 13 serum metabolites in hydrocortisone-withdrawal rats, involving carbohydrates, lipids, and amino acids. The most prominent effect of JKSQ was on the changes of FFAs and some [product FFA]/[precursor FFA] ratios, which represent estimated desaturase and elongase activities. The opposite metabolic responses of JKSQ in adrenal insufficiency rats and normal rats highlighted the "Bian Zheng Lun Zhi" (treatment based on ZHENG differentiation) guideline of TCM and suggested that altered fatty acid metabolism was associated with adrenal insufficiency after glucocorticoid withdrawal and the protective effects of JKSQ.

A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals.

Increasing evidences support that metabolically healthy obese (MHO) is a transient state. However, little is known about the early markers associated with the development of metabolic abnormalities in MHO individuals. Serum free fatty acids (FFAs) profile is highlighted in its association with obesity-related insulin resistance, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). To examine the association of endogenous fatty acid metabolism with future development of metabolic abnormalities in MHO individuals, we retrospectively analyzed 24 [product FFA]/[precursor FFA] ratios in fasting sera and clinical data from 481 individuals who participated in three independent studies, including 131 metabolic healthy subjects who completed the 10-year longitudinal Shanghai Diabetes Study (SHDS), 312 subjects cross-sectionally sampled from the Shanghai Obesity Study (SHOS), and 38 subjects who completed an 8-week very low carbohydrate diet (VLCD) intervention study. Results showed that higher baseline level of oleic acid/stearic acid (OA/SA), and lower levels of stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with higher rate of MHO to MUO conversion in the longitudinal SHDS. Further, the finding was validated in the cross-sectional and interventional studies. This panel of FFA ratios could be used for identification and early intervention of at-risk obese individuals.

The Brain Metabolome of Male Rats across the Lifespan.

Comprehensive and accurate characterization of brain metabolome is fundamental to brain science, but has been hindered by technical limitations. We profiled the brain metabolome in male Wistar rats at different ages (day 1 to week 111) using high-sensitivity and high-resolution mass spectrometry. Totally 380 metabolites were identified and 232 of them were quantitated. Compared with anatomical regions, age had a greater effect on variations in the brain metabolome. Lipids, fatty acids and amino acids accounted for the largest proportions of the brain metabolome, and their concentrations varied across the lifespan. The levels of polyunsaturated fatty acids were higher in infancy (week 1 to week 3) compared with later ages, and the ratio of omega-6 to omega-3 fatty acids increased in the aged brain (week 56 to week 111). Importantly, a panel of 20 bile acids were quantitatively measured, most of which have not previously been documented in the brain metabolome. This study extends the breadth of the mammalian brain metabolome as well as our knowledge of functional brain development, both of which are critically important to move the brain science forward.

Potential Medicinal Application and Toxicity Evaluation of Extracts from Bamboo Plants.

Bamboo plants play a significant role in traditional Asian medicine, especially in China and Japan. Biomedical investigations on the health-benefiting effects as well as toxicity of different parts and species of bamboo have been carried out worldwide since the 1960s, and documented a wide range of protective effects of bamboo-derived products, such as protection against oxidative stress, inflammation, lipotoxicity, cancer, and cardiovascular disease. Some of these products may interfere with male and female reproductive function, thyroid hormone metabolism, and hepatic xenobiotransformation enzymes. The diversity of bamboo species, parts of the plants available for medicinal use, and different extraction methods suggest that bamboo has great potential for producing a range of extracts with functional utility in medicine.

Independent and co-morbid HIV infection and Meth use disorders on oxidative stress markers in the cerebrospinal fluid and depressive symptoms.

Both HIV infection and Methamphetamine (Meth) use disorders are associated with greater depressive symptoms and oxidative stress; whether the two conditions would show additive or interactive effects on the severity of depressive symptoms, and whether this is related to the level of oxidative stress in the CNS is unknown. 123 participants were evaluated, which included 41 HIV-seronegative subjects without substance use disorders (Control), 25 with recent (<6 months) moderate to severe Meth use disorders (Meth), 34 HIV-seropositive subjects without substance use disorders (HIV) and 23 HIV+Meth subjects. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D), and oxidative stress markers were evaluated with glutathione (GSH), 4-hydroxynonenal (HNE), and activities of gamma-glutamyltransferase (GGT) and glutathione peroxidase (GPx) in the cerebrospinal fluid (CSF). Compared with Controls, HIV subjects had higher levels of HNE (+350%) and GGT (+27%), and lower level of GSH (-34%), while Meth users had higher levels of GPx activity (+23%) and GSH (+30 %). GGT correlated with GPx, and with age, across all subjects (p < 0.0001). CES-D scores correlated with CSF HNE levels only in Control and HIV groups, but not in Meth and HIV+Meth groups. HIV and Meth use had an interactive effects on depressive symptoms, but did not show additive or interactive effects on oxidative stress. The differential relationship between depressive symptoms and oxidative stress response amongst the four groups suggest that depressive symptoms in these groups are mediated through different mechanisms which are not always related to oxidative stress.

Roles of glutathione in antioxidant defense, inflammation, and neuron differentiation in the thalamus of HIV-1 transgenic rats.

Inflammation and oxidative stress in the brain are major causes of HIV-associated neurocognitive disorders. Previously we have reported high content of glutathione (GSH) in the thalamus of rats with F344 genetic background. In this study, we investigated the changes of GSH metabolism and GSH-dependent antioxidant enzymes in the rat thalamus in response to HIV-1 transgenesis, and their associations with oxidative stress, inflammation, and neuronal development. Male HIV-1 transgenic (HIV-1Tg) rats and wild type F344 rats at 10 months were used in this study, with 5 rats in each group. Parameters measured in this study included: total and oxidized GSH, glutathione peroxidase (GPx), glutathione-S-transferase (GST), gamma-glutamylcysteine synthetase (GCS), gamma-glutamyl transferase (GGT), cysteine/cystine transporters, 4-hydroxynonenal (HNE), interleukin 12 (IL12), neuronal nuclei (NeuN), microtubule-associated protein (MAP2), and glia fibrillary acidic protein (GFAP). The levels of total GSH, oxidized GSH (GSSG) and MAP2 protein, and enzymatic activities of GCS, GPx and GST were significantly higher in HIV-1Tg rats compared with F344 rats, but the ratio of GSSG/GSH, activity of GGT and levels of HNE, NeuN protein and GFAP protein did not change. HIV-1Tg rats showed a lower level of IL12 protein. GSH positively correlated with GCS, GST and MAP2, GSSG/GSH ratio positively correlated with HNE and IL12, the activities of GPx, GST and GCS positively correlated with each other, and negatively correlated with HNE. These findings suggest an important role of the GSH-centered system in reducing oxidative stress and neuroinflammation, and enhancing neuron differentiation in the thalamus of HIV-1Tg rats.

Methamphetamine decreases levels of glutathione peroxidases 1 and 4 in SH-SY5Y neuronal cells: protective effects of selenium.

Methamphetamine interferes with dopamine reuptake, and the resulting increased dopamine oxidation that creates oxidative stress can lead to degeneration of dopaminergic terminals. Previous studies have shown that the trace element selenium protects against methamphetamine toxicity. However, the specific selenoproteins responsible for protection have not been elucidated. Glutathione peroxidases 1 and 4 (GPx1 and GPx4) incorporate selenium into the amino acid selenocysteine, and their known antioxidant functions make them good candidates for protection from methamphetamine-induced oxidative damage. We differentiated SH-SY5Y neuronal cells in serum-free media with defined supplement containing 0, 10 and 100 nM selenium, and then challenged the cells with a 24-h exposure to methamphetamine. We found that 100 µM methamphetamine decreased GPx1 and GPx4 protein levels. However, both proteins were upregulated with increasing media selenium concentration. GPx enzymatic activity was also increased by selenium and decreased by methamphetamine and correlated with GPx protein levels. Total glutathione levels were reduced by methamphetamine at lower selenium conditions, while the oxidized fraction of GSH was increased at higher selenium levels. Additionally, we observed an increased generation of reactive oxygen species with methamphetamine exposure in media with 0 nM selenium, which was ameliorated by selenium supplementation. These results show that methamphetamine increases oxidative stress by reducing GPx levels, and this can be reversed with addition of selenium. These findings have important implications for treating patients with acute methamphetamine toxicity.

Regional variations of antioxidant capacity and oxidative stress responses in HIV-1 transgenic rats with and without methamphetamine administration.

HIV infection and methamphetamine (Meth) abuse both may lead to oxidative stress. This study used HIV-1 transgenic (HIV-1Tg) rats to investigate the independent and combined effects of HIV viral protein expression and low dose repeated Meth exposure on the glutathione (GSH)-centered antioxidant system and oxidative stress in the brain. Total GSH content, gene expression and/or enzymatic activities of glutamylcysteine synthetase (GCS), gamma-glutamyltransferase (GGT), glutathione reductase (GR), glutathione peroxidase (GPx), glutaredoxin (Glrx), and glutathione-s-transferase (GST) were measured. The protein expression of cystine transporter (xCT) and oxidative stress marker 4-hydroxynonenal (HNE) were also analyzed. Brain regions studied include thalamus, frontal and remainder cortex, striatum, cerebellum and hippocampus. HIV-1Tg rats and Meth exposure showed highly regional specific responses. In the F344 rats, the thalamus had the highest baseline GSH concentration and potentially higher GSH recycle rate. HIV-1Tg rats showed strong transcriptional responses to GSH depletion in the thalamus. Both HIV-1Tg and Meth resulted in decreased GR activity in thalamus, and decreased Glrx activity in frontal cortex. However, the increased GR and Glrx activities synergized with increased GSH concentration, which might have partially prevented Meth-induced oxidative stress in striatum. Interactive effects between Meth and HIV-1Tg were observed in thalamus on the activities of GCS and GGT, and in thalamus and frontal cortex on Glrx activity and xCT protein expression. Findings suggest that HIV viral protein and low dose repeated Meth exposure have separate and combined effects on the brain's antioxidant capacity and the oxidative stress response that are regional specific.

Impact of sustained exposure to ß-amyloid on calcium homeostasis and neuronal integrity in model nerve cell system expressing α4ß2 nicotinic acetylcholine receptors.

Although the interaction between ß-amyloid (Aß) and nicotinic acetylcholine receptors has been widely studied, the impact of prolonged exposure to Aß on nAChR expression and signaling is not known. In this study, we employed a neuronal culture model to better understand the impact of sustained exposure of Aß on the regulation of cellular and synaptic function. The differentiated rodent neuroblastoma cell line NG108-15 expressing exogenous high-affinity α4ß2 nAChRs was exposed to soluble oligomeric Aß for several days. Ca(2+) responses, expression levels of α4ß2 nAChRs, rate of mitochondrial movement, mitochondrial fission, levels of reactive oxygen species, and nuclear integrity were compared between Aß-treated and untreated cells, transfected or not (mock-transfected) with α4ß2 nAChRs. Sustained exposure of Aß(1-42) to α4ß2 nAChR-transfected cells for several days led to increased Ca(2+) responses on subsequent acute stimulation with Aß(1-42) or nicotine, paralleled by increased expression levels of α4ß2 nAChRs, likely the result of enhanced receptor recycling. The rate of mitochondrial movement was sharply reduced, whereas the mitochondrial fission protein pDrp-1 was increased in α4ß2 nAChR-transfected cells treated with Aß(1-42). In addition, the presence of α4ß2 nAChRs dramatically enhanced Aß(1-42)-mediated increases in reactive oxygen species and nuclear fragmentation, eventually leading to apoptosis. Our data thus show disturbed calcium homeostasis coupled with mitochondrial dysfunction and loss of neuronal integrity on prolonged exposure of Aß in cells transfected with α4ß2 nAChRs. Together, the results suggest that the presence of nAChRs sensitizes neurons to the toxic actions of soluble oligomeric Aß, perhaps contributing to the cholinergic deficit in Alzheimer disease.

Phyllostachys edulis compounds inhibit palmitic acid-induced monocyte chemoattractant protein 1 (MCP-1) production.

BACKGROUND: Phyllostachys edulis Carriere (Poaceae) is a bamboo species that is part of the traditional Chinese medicine pharmacopoeia. Compounds and extracts from this species have shown potential applications towards several diseases. One of many complications found in obesity and diabetes is the link between elevated circulatory free fatty acids (FFAs) and chronic inflammation. This study aims to present a possible application of P. edulis extract in relieving inflammation caused by FFAs. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is a pro-inflammatory cytokine implicated in chronic inflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) are transcription factors activated in response to inflammatory stimuli, and upregulate pro-inflammatory cytokines such as MCP-1. This study examines the effect of P. edulis extract on cellular production of MCP-1 and on the NF-κB and AP-1 pathways in response to treatment with palmitic acid (PA), a FFA. METHODOLOGY/PRINCIPAL FINDINGS: MCP-1 protein was measured by cytometric bead assay. NF-κB and AP-1 nuclear localization was detected by colorimetric DNA-binding ELISA. Relative MCP-1 mRNA was measured by real-time quantitative PCR. Murine cells were treated with PA to induce inflammation. PA increased expression of MCP-1 mRNA and protein, and increased nuclear localization of NF-κB and AP-1. Adding bamboo extract (BEX) inhibited the effects of PA, reduced MCP-1 production, and inhibited nuclear translocation of NF-κB and AP-1 subunits. Compounds isolated from BEX inhibited MCP-1 secretion with different potencies. CONCLUSIONS/SIGNIFICANCE: PA induced MCP-1 production in murine adipose, muscle, and liver cells. BEX ameliorated PA-induced production of MCP-1 by inhibiting nuclear translocation of NF-κB and AP-1. Two O-methylated flavones were isolated from BEX with functional effects on MCP-1 production. These results may represent a possible therapeutic application of BEX and its compounds toward alleviating chronic inflammation caused by elevated circulatory FFAs.

Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes.

Monocyte Chemoattractant Protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past two decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized.

Effects of a high-fat diet and bamboo extract supplement on anxiety- and depression-like neurobehaviours in mice.

High-fat diet is a major causative factor of overweight and obesity, which are associated with an increased risk of neuropsychiatric diseases, such as anxiety and depression. In the present study, we investigated the protective effects of bamboo extract (BEX) on anxiety- and depression-like neurobehaviours in mice treated with a high-fat diet. Male mice with CD-1 genetic background were treated for 2 months with either a standard or a high-fat diet (10 or 45 % energy from fat, respectively), with or without the BEX supplement (11 g dry mass per 17 MJ). The anxiety levels of mice were evaluated using open-field and hole-board tests, and depression was measured using the force-swimming test. The anxiety responses of the animals were found significantly increased after the high-fat diet treatment, and this elevation was effectively abolished by the BEX supplement. The high-fat diet seemed to have an anti-depressive effect in mice at the tested time point, but the effect of the BEX supplement on the depression level of the animals was not conclusive. The high-fat diet significantly decreased total glutathione content in the blood while the BEX supplement increased glutathione oxidation. In summary, the present study shows that decreased total glutathione concentration in the blood co-occurred with a high-fat treatment, high anxiety level and low depression level in mice, and when supplemented in a high-fat diet, BEX had an anxiolytic effect in mice.

Supplement of bamboo extract lowers serum monocyte chemoattractant protein-1 concentration in mice fed a diet containing a high level of saturated fat.

Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine up-regulated in obese subjects, contributing to the development of type 2 diabetes. The present study investigated the inhibitory effect of an ethanol-water extract from bamboo (BEX, Phyllostachys edulis) on the blood concentration of MCP-1. C57BL/6J mice were fed a standard diet or a high-fat diet with or without the BEX supplement (11 g dry mass/17 000 kJ) for 6 months. A total of ten mice were used in each group. Body weight and food consumption were measured weekly. After euthanisation, the weight of visceral fat and circulating MCP-1 concentration were measured. In comparison with the standard control group, the high-fat control group had increased body weight, abdominal fat storage and serum MCP-1 concentration by 60 % (P < 0·001), 266 % (P < 0·001) and 180 % (P < 0·01), respectively. In comparison with the high-fat control group, the high-fat BEX group showed a 3 % decrease in body weight (P < 0·01), 24 % decrease in mesenteric fat depot (P < 0·01) and 49 % decrease in serum MCP-1 concentration (P < 0·05). The present study suggests that the BEX supplement in the high-fat diet ameliorates elevated MCP-1 concentrations in the blood, and whether this is related to modulated endocrine properties of the visceral fat is to be studied.