In vitro and in vivo protective potential of quercetin-3-glucuronide against lipopolysaccharide-induced pulmonary injury through dual activation of nuclear factor-erythroid 2 related factor 2 and autophagy.

In vitro and in vivo models of lipopolysaccharide (LPS)-induced pulmonary injury, quercetin-3-glucuronide (Q3G) has been previously revealed the lung-protective potential via downregulation of inflammation, pyroptotic, and apoptotic cell death. However, the upstream signals mediating anti-pulmonary injury of Q3G have not yet been clarified. It has been reported that concerted dual activation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and autophagy may prove to be a better treatment strategy in pulmonary injury. In this study, the effect of Q3G on antioxidant and autophagy were further investigated. Noncytotoxic doses of Q3G abolished the LPS-caused cell injury, and reactive oxygen species (ROS) generation with inductions in Nrf2-antioxidant signaling. Moreover, Q3G treatment repressed Nrf2 ubiquitination, and enhanced the association of Keap1 and p62 in the LPS-treated cells. Q3G also showed potential in inducing autophagy, as demonstrated by formation of acidic vesicular organelles (AVOs) and upregulation of autophagy factors. Next, the autolysosomes formation and cell survival were decreased by Q3G under pre-treatment with a lysosome inhibitor, chloroquine (CQ). Furthermore, mechanistic assays indicated that anti-pulmonary injury effects of Q3G might be mediated via Nrf2 signaling, as confirmed by the transfection of Nrf2 siRNA. Finally, Q3G significantly alleviated the development of pulmonary injury in vivo, which may result from inhibiting the LPS-induced lung dysfunction and edema. These findings emphasize a toxicological perspective, providing new insights into the mechanisms of Q3G's protective effects on LPS-induced pulmonary injury and highlighting its role in dual activating Nrf2 and autophagy pathways.

Therapeutic Effect of Desmodium caudatum Extracts on Alleviating Diabetic Nephropathy Mice.

Desmodium caudatum extracts (DCE) were investigated for their potential therapeutic effects on diabetic nephropathy (DN). In our study, the high-fat diet (HFD) / streptozotocin (STZ)-induced DN model in C57BL/6 mice was treated with 100 mg/kg, 200 mg/kg DCE. The results showed that DCE decreased biochemical parameters and proteinuria levels. The kidney sections staining indicated that DCE treatment recovered glomerular atrophy and alleviated lipid droplets in the glomerular. Additionally, DCE inhibited lipid and glycogen accumulation down-regulated the expression of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) proteins. DCE also reduced collagenous fibrous tissue and the expression of transforming growth factor-ß1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) through Masson's trichrome staining and immunohistochemical analysis. We found that DCE alleviated hydroxyproline content, and epithelial-mesenchymal transition (EMT). Besides, the results shown that DCE enhanced the antioxidant enzymes to mitigate fibrosis by reducing oxidative stress. In conclusion, our study provided evidence of the protective effect of DCE which down-regulated hyperglycemia, hyperlipidemia and inhibition of TGF-ß1 and EMT pathway but elevated antioxidant, suggesting its therapeutic implication for DN.

Anti-Hypertensive Effect of Solanum muricatum Aiton Leaf Extract In Vivo and In Vitro.

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation.

Autophagic effects of Hibiscus sabdariffa leaf polyphenols and epicatechin gallate (ECG) against oxidized LDL-induced injury of human endothelial cells.

PURPOSE: Oxidized low-density lipoprotein (ox-LDL) contributes to the pathogenesis of atherosclerosis by promoting vascular endothelial cell injury. Hibiscus sabdariffa leaf polyphenols (HLP), rich in flavonoids, have been shown to possess antioxidant and antiatherosclerotic activities. In this study, we examined the protective role of HLP and its main compound (-)-epicatechin gallate (ECG) in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL in vitro. METHODS: In a model of ox-LDL-impaired HUVECs, assessments of cell viability, cytotoxicity, cell proliferation, apoptosis, and autophagy were detected. To highlight the mechanisms of the antiapoptotic effects of HLP and ECG, the expressions of molecular proteins were measured by Western blotting, real-time PCR, and so on. RESULTS: HLP or ECG improved the survival of HUVECs from ox-LDL-induced viability loss. In addition, HLP or ECG showed potential in reducing ox-LDL-dependent apoptosis. Next, the ox-LDL-induced formation of acidic vesicular organelles and upregulation of the autophagy-related genes were increased by HLP or ECG. The HLP-triggered autophagic flux was further confirmed by increasing the LC3-II level under the pretreatment of an autophagy inhibitor chloroquine. Molecular data indicated the autophagic effect of HLP or ECG might be mediated via class III PI3K/Beclin-1 and PTEN/class I PI3K/Akt cascade signaling, as demonstrated by the usage of a class III PI3K inhibitor 3-methyladenine (3-MA) and a PTEN inhibitor SF1670. CONCLUSIONS: Our data imply that ECG-enriched HLP upregulates the autophagic pathway, which in turn led to reduce ox-LDL-induced HUVECs injury and apoptosis and provide a new mechanism for its antiatherosclerotic activity.

Houttuynia cordata aqueous extract attenuated glycative and oxidative stress in heart and kidney of diabetic mice.

PURPOSE: The anti-glycative and anti-oxidative effects from Houttuynia cordata leaves aqueous extract (HCAE) in heart and kidney of diabetic mice were examined. METHODS: HCAE, at 1 or 2 %, was supplied in drinking water for 8 weeks. Plasma glucose and blood urea nitrogen (BUN) levels and creatine phosphokinase (CPK) activity were measured. The production of oxidative and inflammatory factors was determined. Activity and protein expression of associated enzymes or regulators were analyzed. RESULTS: HCAE intake at both doses lowered plasma glucose and BUN levels, and CPK activity and also restored creatinine clearance rate in diabetic mice. HCAE intake, only at 2 %, retained plasma insulin levels (P < 0.05). HCAE reduced reactive oxygen species, protein carbonyl, interleukin-6, tumor necrosis factor-alpha, N (ε) -(carboxymethyl)-lysine, pentosidine and fructose levels, and reserved glutathione content in heart and kidney of diabetic mice (P < 0.05). Diabetes enhanced aldose reductase (AR) activity and protein expression in heart and kidney (P < 0.05). HCAE intake at both doses decreased renal AR activity and protein expression, but only at 2 % lowered cardiac AR activity and protein expression (P < 0.05). Diabetes increased protein expression of RAGE, p47(phox) and gp91(phox), nuclear factor kappa-B (NF-κB) p50, NF-κB p65 and mitogen-activated protein kinase in heart and kidney (P < 0.05). HCAE intake only at 2 % limited RAGE expression, but at 1 and 2 % downregulated p47(phox), NF-κB p65 and p-p38 expression in these organs (P < 0.05). CONCLUSIONS: These findings suggest that Houttuynia cordata leaves aqueous extract could ameliorate cardiac and renal injury under diabetic condition.

Protective Effects of Red Guava on Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes is an important chronic disease and the 4th leading cause of death in Taiwan. Hyperglycemia-induced oxidative and inflammatory damage are the main causes of chronic complications in diabetic patients. The red guava (red-fleshed guava cultivar of Psidium guajava L.) is a tropical fruit belonging to the Myrtaceae family and an important commercial crop in Taiwan. In this study, the protective effects of a diet containing red guava on inflammation and oxidative stress in streptozotocin (STZ)-induced diabetic mice were examined. The experimental group was divided into seven subgroups: normal (N), diabetes mellitus (DM), diabetes + red guava 1% (L), 2% (M), and 5% (H), diabetes + 5% red guava + anti-diabetic rosiglitazone (HR), and diabetes + anti-diabetic rosiglitazone (R). The mice were fed for 8 weeks and sacrificed by decapitation. Compared with the DM group, the experimental groups with diets containing red guava as well as rosiglitazone all showed significant improvements in blood glucose control, insulin resistance, creatinine, blood urea nitrogen, triglycerides, non-esterified fatty acids, cholesterol, c-reactive protein, TNF-α, and IL-10. Furthermore, the expression of inflammatory proteins, such as iNOS and NF-κB, was suppressed via activated PPARγ, and the expression levels of GPx3 and ACO increased. In summary, red guava can significantly suppress inflammatory and oxidative damage caused by diabetes and alleviate diabetic symptoms; thus, it exerts protective effects and has potential applications for the development of a dietary supplement.

The effect of isovitexin on lipopolysaccharide-induced renal injury and inflammation by induction of protective autophagy.

Chronic kidney disease (CKD) is a systemic inflammatory syndrome that includes tubulointerstitial inflammation. Lipopolysaccharide (LPS), the outer membrane of Gram-negative bacteria, can increase reactive oxygen species production (ROS) that triggers cell inflammation. Isovitexin (IV) is a flavone that has the potential for anticancer, antioxidant, and anti-inflammatory. This study aimed to hypothesize that IV inhibited LPS-induced renal injury in vitro and in vivo. In vitro study, IV prevented LPS-induced ROS production and increased cell viability on SV40-MES-13 cells. Additionally, IV ameliorated mitochondrial membrane potential, downregulated inflammation and pyroptosis factors on LPS treatment. We found that LPS treatment reduced the expression of autophagy, however, this effect was reversed by IV. In vivo study, the renal injury model in C57BL/6 mice cotreatment with IV was examined. In addition, IV decreased LPS-induced glomerular atrophy and reduced inflammation-related cytokines releases. Further showed that IV could significantly reduce LPS-induced inflammation and pyroptosis factors in mice. Under the immunostaining, increased fluorescence of LC3 autophagy-related protein was recovered by IV. In summary, IV ameliorated renal injury, inflammation and increased protected autophagy by anti-ROS production, anti-inflammation, and anti-pyroptosis. In the future, the safety of isovitexin as a novel perspective for CKD patients should be evaluated in further clinical studies.

Protective effects of an aqueous extract from pepino (Solanum muricatum Ait.) in diabetic mice.

BACKGROUND: This study analysed the content of ascorbic acid, phenolic acids and flavonoids in aqueous and ethanol extracts of pepino (Solanum muricatum Ait.), and examined the protective effects of pepino aqueous extract (PAE) in a mouse model of diabetes. PAE at 1, 2 and 4% was supplied for 5 weeks. RESULTS: Aqueous and ethanol extracts had similar levels of total phenolic acids, but PAE had a higher content of ascorbic acid and total flavonoids than the ethanol extract. PAE treatments at 2% and 4% significantly lowered plasma glucose level (P < 0.05); however, only the 4% PAE significantly elevated plasma insulin level at week 5 (P < 0.05). PAE treatments significantly decreased the levels of malonyldialdehyde and reactive oxygen species in kidney (P < 0.05); however, only the 2% and 4% treatments significantly reduced oxidised glutathione formation, increased glutathione level, and retained renal glutathione peroxidase and catalase activities (P < 0.05). PAE treatments at 2% and 4% significantly lowered renal interleukin (IL)-6 and tumour necrosis factor-α levels (P < 0.05); however, only the 4% treatments significantly diminished renal IL-1ß and levels of monocyte chemoattractant protein-1 (P < 0.05). PAE treatments at 4% significantly decreased aldose reductase activity and sorbitol production in kidney (P < 0.05). CONCLUSION: These findings support the suggestion that pepino aqueous extract could attenuate the progression of diabetes via its antioxidative, anti-inflammatory and antiglycative effects.

Association of dietary AGEs with circulating AGEs, glycated LDL, IL-1α and MCP-1 levels in type 2 diabetic patients.

PURPOSE: The association of dietary advanced glycation endproducts (AGEs) intake with the oxidative and inflammatory status in type 2 diabetic patients was examined. METHODS: Seventy-four healthy controls, 50 low AGEs intake and 68 high AGEs intake type 2 diabetic patients were requested to complete a 7-day dietary record. Blood levels of several oxidative and inflammatory biomarkers were determined. RESULTS: Diabetic patients with high AGEs intake had significantly elevated plasma levels of AGEs, HbA1c, low-density lipoprotein (LDL), LDL-cholesterol and glycated LDL than low AGEs intake patients and controls (P < 0.05). These high AGEs intake patients also had significantly increased plasma levels of 8-isoprostane, interleukin (IL)-1α, tumor necrosis factor-α, monocyte chemoattractant protein (MCP)-1 and lower superoxide dismutase (SOD) activity than low AGEs intake patients (P < 0.05). Correlation coefficients of dietary AGEs versus plasma AGEs, HbA1c, 8-isoprostane, IL-1α and MCP-1 were >0.6; but the correlation coefficient of dietary AGEs versus plasma SOD activity was <-0.6. CONCLUSION: Increasing dietary AGEs intake might enrich circulating AGE level and contribute to oxidative and inflammatory progression under diabetic condition. The circulating 8-isoprostane, IL-1α and MCP-1 levels and SOD activity might be appropriate biomarkers used to evaluate dietary AGEs-associated oxidative and inflammatory stress.

Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans.

SCUBE2 [signal peptide, CUB domain, EGF (epidermal growth factor)-like protein 2] belongs to an evolutionarily conserved SCUBE protein family, which possesses domain organization characteristic of an N-terminal signal peptide sequence followed by nine EGF-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C-terminus. Despite several genetic analyses suggesting that the zebrafish orthologue of the mammalian SCUBE2 gene participates in HH (Hedgehog) signalling, the complete full-length cDNA and biochemical function for mammalian SCUBE2 on HH signalling remains uninvestigated. In the present study, we isolated the full-length cDNA and studied the role of human SCUBE2 in the HH signalling cascade. When overexpressed, recombinant human SCUBE2 manifests as a secreted surface-anchored glycoprotein. Deletion mapping analysis defines the critical role of the spacer region and/or cysteine-rich repeats for membrane association. Further biochemical analyses and functional reporter assays demonstrated that human SCUBE2 can specifically interact with SHH (Sonic Hedgehog) and SHH receptor PTCH1 (Patched-1), and enhance the SHH signalling activity within the cholesterol-rich raft microdomains of the plasma membranes. Together, our results reveal that human SCUBE2 is a novel positive component of the HH signal, acting upstream of ligand binding at the plasma membrane. Thus human SCUBE2 could play important roles in HH-related biology and pathology, such as during organ development and tumour progression.

To Buy or Not to Buy? Consumer Attitudes and Purchase Intentions for Suboptimal Food.

Food system and food safety have drawn spontaneous global attention due to the effect of substantial environmental concerns. Three billion tons of food are wasted every year, estimated as being a third of all produced food. The production of much of this waste is directly linked to the unwillingness to sell, purchase, and consume suboptimal food that have deviated from regular products in terms of appearance standards, date labeling, or damaged packaging. Yet empirical research on this issue is scarce. This study aims to develop an extended Theory of Planned Behavior (TPB) research model, which includes environmental concern and sensory appeal to predict consumers' purchase intention to suboptimal foods. A total of 539 respondents collected in Taiwan as data input. The empirical results of structural equation modeling (SEM) indicate that consumers' attitude was the main predictor of their intention to purchase suboptimal foods. Interestingly, this research showed that both perceived behavioral control and subjective norms were not significant predictors of intention. Furthermore, adding environmental concern and sensory appeal as the additional constructs to the TPB significantly increased the explanatory power of the standard model. These findings provide important insights for suboptimal food and useful recommendations for marketing channels, suggesting that promotion of suboptimal food may be the key to potential business.

Aqueous Extract of Pepino (Solanum muriactum Ait) Leaves Ameliorate Lipid Accumulation and Oxidative Stress in Alcoholic Fatty Liver Disease.

Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber⁻DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-α, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-κB) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation.

Matrix metalloproteinase-2, -9 and -13 are involved in fibronectin degradation of rat lung granulomatous fibrosis caused by Angiostrongylus cantonensis.

Pulmonary granuloma formation and fibrosis were experimentally induced in Sprague-Dawley strain rats by Angiostrongylus cantonensis. Increased protein levels of matrix metalloproteinase (MMP)-2, -9, -13 and the imbalance between these enzymes and metalloproteinase inhibitors, tissue inhibitors of MMPs (TIMP-1 and -2), occur during granulomatous fibrosis. Activation of proteolytic enzymes (MMP-2, -9 and -13) and fibronectin degradation occur simultaneously. Furthermore, the present study demonstrated that fibronectin avidly binds MMP-2, -9 or -13. Immunohistochemical observations also showed the localization of MMP-13, TIMP-1 and -2 within the infiltrating leucocytes. These results suggest that MMP-2, -9 and -13 may participate in the fibronectin degradation of A. cantonensis-induced granulomatous fibrosis.

Antiinflammatory and antifibrogenic effects of s-ethyl cysteine and s-methyl cysteine in the kidney of diabetic mice.

Protective effects of s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) in kidney of diabetic mice were examined. SEC and SMC at 0.5, 1, 1.5, 2 g/L were added to the drinking water for 6 wk. Results showed that the intake of SEC or SMC alleviated body weight loss and urine output, as well as markedly decreased plasma blood urea nitrogen (BUN) and creatinine clearance (CCr) in diabetic mice (P < 0.05). The intake of SEC caused significantly dose-dependent increase in insulin and decrease in blood glucose, urinary albumin and type IV collagen (P < 0.05). SEC and SMC intake significantly and dose-dependently decreased malondialdehyde level and increased glutathione content in kidney (P < 0.05). The intake of these agents also increased renal GPx activity (P < 0.05), but there was no dose-dependent effect. SEC treatments dose-dependently decreased IL-6 and TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10 mRNA expression (P < 0.05). SMC treatments significantly suppressed renal IL-6 and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P < 0.05). SEC or SMC intake significantly suppressed renal TGF-beta1 level and renal PKC activity (P < 0.05); however, only SEC treatments showed dose-dependent effect. SEC and SMC treatments significantly down-regulated mRNA expression of renal TGF-beta1 (P < 0.05), only SEC treatments had dose-dependent effects. Based on the observed antioxidative, antiinflammatory, and antifibrogenic effects, the supplement of SEC or SMC might be helpful for the prevention or treatment of diabetic kidney diseases.

Antioxidative and anti-inflammatory effects of four cysteine-containing agents in striatum of MPTP-treated mice.

OBJECTIVES: Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to examine the neuroprotective effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-methyl cysteine (SMC), and s-propyl cysteine (SPC). METHODS: Each agent at 1 g/L was directly added to the drinking water for 3 wk. Mice were treated by subcutaneous injection of MPTP (24 mg/kg body weight) for 6 consecutive days. The brain from each mouse was quickly removed and the striatum was collected for analyses. RESULTS: The MPTP treatment significantly depleted striatal glutathione content, reduced the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase, increased malondialdehyde level, and elevated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in striatum (P < 0.05). The pre-intake of NAC, SEC, SMC, and SPC significantly attenuated MPTP-induced glutathione loss, retained the activity of GPX and SOD, diminished oxidative stress, and suppressed MPTP-induced elevation of IL-6 and TNF-alpha (P < 0.05). MPTP treatment significantly suppressed GPX mRNA expression and enhanced TNF-alpha mRNA expression (P < 0.05). Compared with MPTP treatment alone, the pre-intake of NAC, SEC, SMC, and SPC significantly elevated GPX mRNA expression and diminished TNF-alpha mRNA expression (P < 0.05), in which SPC showed the greatest suppressive effect against MPTP-induced TNF-alpha mRNA expression (P < 0.05). Dopamine and 3,4-dihydroxyphenylacetic acid contents in the striatum were significantly decreased by MPTP treatment (P < 0.05). The pre-intake of four test agents significantly improved MPTP-induced dopamine depletion and increased dopamine/3,4-dihydroxyphenylacetic acid content (P < 0.05). CONCLUSION: These results suggest that these cysteine-containing compounds could provide antioxidative and anti-inflammatory protection for the striatum against the development of Parkinson's disease.

Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level.

BACKGROUND: Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats. METHODS: One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured. RESULTS: Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea. CONCLUSION: These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.

Effects of apomorphine on the expression of learned helplessness behavior.

Dopaminergic system and its D1 as well as D2 receptors are involved in the modulation of emotional behavior. This experiment investigated the role of dopaminergic activity in the inescapable stress-induced learned helplessness, a widely used depression animal model, by using the pharmacological manipulation through the apomorphine (APO), an agonist for D1 and D2 receptors, and sulpiride (SUL), a selective D2 antagonist. Male Sprague Dawley rats were used and tested in a shuttle box. In the day-1 session, the rats received a 10-trial (1 min/trial) inescapable stressor: a 3 sec conditioned stimulus (CS; 75 db sound and 250 lux red light) followed by a 10 sec unconditioned stimulus (UCS; electrical foot shock, 0.5 mA). In the day-2 session, a 15-trial active avoidance test, 3 sec CS followed by UCS, was performed 30 min after the administration of APO (0, 0.05, 0.5, 1, and 5 mg/kg, i.p.). The number of failures was counted and the UCS was stopped when the rats did not escape after 15 sec UCS. The results showed that APO at the dosage of 0.5 mg/kg had a tendency to enhance the avoidance behavior. In contrast, the treatment of higher dose of APO, 1 and 5 mg/kg, reduced the number of escape but increased the number of failure. Pretreatment of SUL (5 mg/kg, i.p.), 10 min before 1 mg/kg of APO, significantly enhanced the failure behavior. The present data suggest that the activity of D2 receptor may be associated with the adaptive or protective role in the prevention of escape deficits after exposure to inescapable stress. However, the excessive stimulation of D1 receptor may participate in the failure of coping behavior leading to learned helplessness and therefore in the pathophysiological mechanisms underling the development of depression.

Taiwanese and Japanese yam (Dioscorea spp.) extracts attenuate doxorubicin-induced cardiotoxicity in mice.

The present study was designed to explore whether yam could protect the heart from doxorubicin (DOX)-induced oxidative stress leading to cardiotoxicity in vivo. In this study, the protective effects of water and ethanol extracts of three varieties of yam, including water extracts of Dioscorea japonica Thunb., ethanol extracts of D. japonica Thunb., water extracts of Dioscorea alata, ethanol extracts of D. alata, water extracts of Dioscorea purpurea, and ethanol extracts of D. purpurea, against DOX-induced cardiotoxicity in experimental mice were evaluated. DOX treatment led to significant decreases in the ratio of heart weight to body weight and heart rate, and increases in blood pressure and the serum level of lactate dehydrogenase, a marker of cardiotoxicity, were recovered by yam extracts, especially in water extracts of D. alata. Yam extracts also decreased the cardiac levels of thiobarbituric acid relative substances, reactive oxygen species, and inflammatory factors, as well as the expression of nuclear factor kappa B, while ethanol extracts of D. japonica Thunb. and D. purpurea were shown to be more potent. Moreover, yam extracts had a role in increasing the activities of glutathione peroxidase and superoxide dismutase, thus improving the DOX-induced alterations in oxidative status in the heart tissue of DOX-treated mice. All ethanol extracts of yam exhibited their antiapoptotic abilities on caspase-3 activation and mitochondrial dysfunction, and ethanol extracts of D. alata still exerted a superior effect. Based on these findings, it can be concluded that yam has significant cardioprotective properties against DOX-induced damage via its multiple effects on antioxidant, anti-inflammatory, or antiapoptotic activities.