Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause.

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.

The difference of castration timing of Korean Hanwoo bulls does not significantly affect the carcass characteristics.

It is already well known that castration improves marbling quality but exact timing of castration is still highly debated in beef cattle production industry. After castration, blood hormonal changes occur in steer and objective of this study was to investigate the effects of growth hormone (GH) levels on adipocyte differentiation in stromal vascular cells (SVCs) and transdifferentiation into adipocytes in C2C12 myoblasts. Total GH concentrations were measured via enzyme-linked immunosorbent assay (ELISA) in 24 male calves and 4 female calves. Cell proliferation, cellular triglyceride (TG) accumulation, and the cell's lipolytic capability were measured in C2C12 myoblasts and SVCs. Myogenic, adipogenic, and brown adipocyte-specific gene expression was measured via real-time polymerase chain reaction (PCR) using SYBR green. Serum GH levels were the highest in late-castrated calves. Treatment with 5 ng/mL GH resulted in greater TG accumulation as well as increased CCAAT-enhancer-binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ expression compared to that after treatment with 15 ng/mL GH. Treatment with 5 ng/mL GH also resulted in lower myogenin (myo)G and myoD expression compared to that after treatment with 15 ng/mL GH. The expression of bone morphogenetic protein (BMP) 7 after treatment with 5 ng/mL GH was higher than that after treatment with 15 ng/mL GH. But carcass characteristics data showed no significant difference between early and late castrated steers. Therefore, our results indicate that castration timing does not seem to be inevitable determinate of carcass qualities, particularly carcass weight and marbling score in Hanwoo beef cattle.

Anticancer Activities of Ginsenosides, the Main Active Components of Ginseng.

Cancer incidence rate has been increasing drastically in recent years. One of the many cancer treatment methods is chemotherapy. Traditional medicine, in the form of complementary and alternative therapy, is actively used to treat cancer, and many herbs and active ingredients of such therapies are being intensely studied to integrate them into modern medicine. Ginseng is traditionally used as a nourishing tonic and for treating various diseases in Asian countries. The therapeutic potential of ginseng in modern medicine has been studied extensively; the main bioactive component of ginseng is ginsenosides, which have gathered attention, particularly for their prospects in the treatment of fatal diseases such as cancer. Ginsenosides displayed their anticancer and antimetastatic properties not only via restricting cancer cell proliferation, viability, invasion, and migration but also by promoting apoptosis, cell cycle arrest, and autophagy in several cancers, such as breast, brain, liver, gastric, and lung cancer. Additionally, ginsenosides can work synergistically with already existing cancer therapies. Thus, ginsenosides may be used alone or in combination with other pharmaceutical agents in new therapeutic strategies for cancer. To date however, there is little systematic summary available for the anticancer effects and therapeutic potential of ginsenosides. Therefore, we have reviewed and discussed all available literature in order to facilitate further research of ginsenosides in this manuscript.

Antioxidant Properties and Diet-Related α-Glucosidase and Lipase Inhibitory Activities of Yogurt Supplemented with Safflower (Carthamus tinctorius L.) Petal Extract.

Recently, yogurt has been extensively studied to further enhance its functions using edible plant extracts. This study was conducted to investigate whether safflower petal (SP) as a natural food additive can be used to develop functional yogurt with improved health benefits. SPs were extracted with ethanol (SPE) and hot water (SPW), and then safflower yogurt was prepared by adding 0%-1.0% of those extracts to plain yogurt. With an increase in the fermentation duration, the pH of SPE and SPW yogurt samples was decreased, whereas titratable acidity and microbial counts were increased. The concentration of total polyphenols and total flavonoids, the activity of antioxidants, and the inhibitory effect on reactive oxygen species (ROS) were higher in SPW yogurt than SPE yogurt. Furthermore, α-glucosidase and lipase activity inhibitory effects of SPW yogurt were higher than those of SPE yogurt. In particular, free radical-scavenging activities, ROS inhibitory effect, and α-glucosidase activity inhibitory effects were significantly increased in SPW yogurt in a dose-dependent manner. Overall, these results suggest that SP extract possesses antioxidant activities and that it can downregulate α-glucosidase and lipase activities. The SP extract may have potential benefits as a natural food additive for the development of functional yogurt.

Biochemical and Antioxidant Activity of Yogurt Supplemented with Paprika Juice of Different Colors.

Paprika is known to contain polyphenolic compounds that have good antioxidant properties. This study was conducted to investigate the benefits of adding paprika juice of different colors to yogurt and to determine how paprika affects the quality characteristics of yogurt. Stirred yogurt samples supplemented with different levels of red, orange, or yellow paprika juice were inoculated with mixes of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. Paprika addition decreased the pH but increased titratable acidity, lactic acid bacteria (LAB) counts, total polyphenol content (TPC), levels of vitamin A and C, and antioxidant activity. Proteolysis and viscosity of paprika-containing yogurts were significantly higher than those of the control yogurt without paprika juice (p<0.05). In particular, the viscosity of red paprika yogurt was significantly higher than that of yogurts containing 5% orange and yellow paprika juices (each p<0.05). The antioxidant activity of the methanol extract of the yogurt containing 2.5% orange paprika juice was the highest. Storage at 4°C for 15 days only slightly altered LAB counts, antioxidant activity, and TPC of paprika yogurt. These results indicate that paprika could be used as a natural food additive for the development of functional yogurts.

Inflammation as the Potential Basis in Depression.

There is growing evidence of the association between inflammation and stress-related disorders including depression. The positive correlation between the increased levels of inflammatory cytokines observed in patients with other diseases and the byproduct of the depressive symptoms may be caused by chronic stress. Increased neuroinflammatory responses are capable of activating microglia and astrocytes, which leads to release pro-inflammatory cytokines. Moreover, elevated levels of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 are causally related to various aspects of depression such as the behavioral symptomatology. Eventually, these elevated cytokines aggravate and propagate neuroinflammation, impairing brain functions. Thus, activated astrocytes and microglia may be potential mediators in neuroinflammatory processes contributing to the development of depression.

Effects of transport stress on physiological responses and milk production in lactating dairy cows.

OBJECTIVE: This study was conducted to investigate the effect of transport stress on physiological and hematological responses and milk performance in lactating dairy cows. METHODS: Ten lactating dairy cows were randomly divided into 2 groups. The treatment group (TG) was transported 200 km for 4 h by truck, and the control group (NTG) was restrained by stanchion for 4 h in Konkuk University farm. Blood and milk samples were collected at 24 h pre-transport; 1, 2, and 4 h during transport; and 2, 24, and 48 h post-transport. Milk yields were measured at 24 h pre-transport, 0 h during transport, and 24, 48, and 72 h post-transport. RESULTS: Leukocyte, neutrophil, and monocyte numbers in the TG were significantly higher than those of the NTG at each experimental time point. Lymphocyte numbers in the TG were significantly (p<0.05) higher than those of the NTG at 48 h post-transport. Additionally, the neutrophil:lymphocyte ratio of the TG was 45% and 46% higher than that of the NTG at 4 h during transport and 2 h post-transport, respectively. There were no significant differences in erythrocyte numbers, hemoglobin concentrations, platelet numbers, and hematocrit percentages between two groups. Cortisol levels in the TG were significantly (p<0.05) higher than those in the NTG. Milk yields in the TG were lower than those in the NTG. The somatic cell count (SCC) of the TG was significantly (p<0.05) higher than that of the NTG at 1 and 2 h during transport; that of the TG increased dramatically at 1 h during transport and gradually decreased subsequently. CONCLUSION: Transport stress increased blood parameters including leucocyte, neutrophil, and monocyte numbers by increased cortisol levels, but did not affect erythrocytes, hemoglobin and hematocrit levels. Additionally, transport resulted in a decrease in milk yield and reduced milk quality owing to an increase in milk SCC.

Big Data Analysis of Genes Associated With Neuropsychiatric Disorders in an Alzheimer's Disease Animal Model.

Alzheimer's disease is a neurodegenerative disease characterized by the impairment of cognitive function and loss of memory, affecting millions of individuals worldwide. With the dramatic increase in the prevalence of Alzheimer's disease, it is expected to impose extensive public health and economic burden. However, this burden is particularly heavy on the caregivers of Alzheimer's disease patients eliciting neuropsychiatric symptoms that include mood swings, hallucinations, and depression. Interestingly, these neuropsychiatric symptoms are shared across symptoms of bipolar disorder, schizophrenia, and major depression disorder. Despite the similarities in symptomatology, comorbidities of Alzheimer's disease and these neuropsychiatric disorders have not been studied in the Alzheimer's disease model. Here, we explore the comprehensive changes in gene expression of genes that are associated with bipolar disorder, schizophrenia, and major depression disorder through the microarray of an Alzheimer's disease animal model, the forebrain specific PSEN double knockout mouse. To analyze the genes related with these three neuropsychiatric disorders within the scope of our microarray data, we used selected 1207 of a total of 45,037 genes that satisfied our selection criteria. These genes were selected on the basis of 14 Gene Ontology terms significantly relevant with the three disorders which were identified by previous research conducted by the Psychiatric Genomics Consortium. Our study revealed that the forebrain specific deletion of Alzheimer's disease genes can significantly alter neuropsychiatric disorder associated genes. Most importantly, most of these significantly altered genes were found to be involved with schizophrenia. Taken together, we suggest that the synaptic dysfunction by mutation of Alzheimer's disease genes can lead to the manifestation of not only memory loss and impairments in cognition, but also neuropsychiatric symptoms.

Glehnia littoralis Root Extract Inhibits Fat Accumulation in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice by Downregulating Adipogenic Gene Expression.

Glehnia littoralis has been reported to have several pharmacological properties but no reports describing the antiadipogenic effect of this plant have been published. This study was conducted to investigate the effects of Glehnia littoralis root hot water extract (GLE) and its underlying mechanism on 3T3-L1 cell adipogenesis and in high-fat diet- (HFD-) induced obese mice. We measured intracellular lipid accumulation using oil red O staining in vitro. For in vivo study, twenty-eight C57BL/6J male mice were randomly divided into four groups, Control, HFD, HFD + 1% GLE, and HFD + 5% GLE, which was performed for eight weeks. We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo.

Phytochemicals and antioxidant capacity of some tropical edible plants.

OBJECTIVE: To find biological functions such as antibacterial and antioxidant activities in several tropical plants and to investigate the possibility of antibiotic substitute agents to prevent and treat diseases caused by pathogenic bacteria. METHODS: Plants such as Poncirus trifoliata fruit (Makrut), Zingiber officinale Rosc (Khing), Areca catechu L. (Mak), Solanum melongena L. I (Makkhuayao), and Solanum melongena L. II (Makhurapro) were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. The free radical scavenging activities were measured using 2-diphenyl-2-picryl hydrazyl photometric assay. Antibacterial activities with a minimum inhibitory concentration (MIC) were observed by agar diffusion assay against pathogenic strains of Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, Clostridium perfringens, and Pantoea agglomerans. RESULTS: Poncirus trifoliata fruit methanol extract showed antibacterial activities against gram-negative and gram-positive pathogens. Additionally, this showed the strongest antibacterial activity against Burkholderia sp. and Haemopilus somnus with MIC 131 µg/mL, respectively. Areca catechu L. water extract showed antibacterial activities against Burkholderia sp., Haemopilus somnus, and Haemopilus parasuis. The MIC value for Haemopilus parasuis was 105 µg/mL in this. Antioxidant activity of Zingiber officinale Rosc n-hexane extract showed 2.23 mg/mL effective concentration 50% (EC50) value was the highest activity among tropical plants extracts. Total polyphenol content in Zingiber officinale Rosc methanol extract was 48.4 µg/mL and flavonoid content was 22.1 µg/mL showed the highest values among tested plants extracts. CONCLUSION: Taken together, these results suggest that tropical plants used in this study may have a potential benefit as an alternative antibiotics agent through their antibacterial and antioxidant activities.

Cnidium officinale Makino extract induces apoptosis through activation of caspase-3 and p53 in human liver cancer HepG2 cells.

A number of diverse studies have reported the anticancer properties of Cnidium officinale Makino (CO). However, the apoptotic effect of this traditional medicinal herb in human hepatocellular carcinoma cells (HepG2) remains to be elucidated. Therefore, the present study investigated the ability of CO to reduce cell viability through apoptotic pathways. Cell viability was determined using the 2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assay. CO extract-induced apoptosis in HepG2 cells was assessed by Hoechst 33258 staining. The cell cycle was monitored using fluorescence-activated cell sorting analysis with propidium iodide staining. Furthermore, the present study explored whether various signaling molecules associated with HepG2 cell death were affected by CO treatment, including caspase-3, B-cell lymphoma 2 (Bcl-2), tumor protein p53 (p53), cyclin-dependent kinase 4 (CDK4) and cyclin D. The expression levels of these genes were examined by reverse-transcription polymerase chain reaction and western blotting. The expression levels of caspase-3 and p53 were upregulated with CO extract treatment, whereas those of Bcl-2, CDK4 and cyclin D were significantly downregulated. Cleaved caspase-3 expression was upregulated following treatment with CO extract in a dose-dependent manner. Collectively, the data suggest that CO extract has the potential to induce apoptosis of HepG2 cells and may act by suppressing the cell cycle, which leads to caspase-3 cleavage and p53 signaling.

Monascus ruber-Fermented Buckwheat (Red Yeast Buckwheat) Suppresses Adipogenesis in 3T3-L1 Cells.

Although various treatments have been used for weight loss to date, obese people rarely have safe and effective treatment options. Therefore, the antiobesity effects of several natural compounds are being actively investigated. This study was conducted to investigate the antiadipogenic effects of Monascus ruber-fermented Fagopyrum esculentum (red yeast buckwheat, RYB) in 3T3-L1 cells. We assessed the intracellular lipid content and adipocyte differentiation by oil red O staining and the expression of genes and proteins associated with adipocyte differentiation by reverse transcription-polymerase chain reaction and western blotting in 3T3-L1 cells. RYB dose dependently inhibited 3T3-L1 cell differentiation at concentrations of 50-800 µg/mL, without cytotoxic effects. It also suppressed the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, and adipocyte-specific genes, such as adipocyte fatty acid-binding protein (aP2), fatty acid synthase, and leptin, during preadipocyte differentiation into adipocytes. Furthermore, RYB reduced cyclin-dependent kinase 2 and cyclin expression and increased p21 and p27 expression, thus causing cell cycle arrest at the G1/S phase. Collectively, these results suggest that RYB may be an effective nutraceutical for weight loss as indicated by its ability to suppress adipogenesis-specific gene expression and cause cell cycle arrest at the G1/S interphase.

Effects of Physically Effective Neutral Detergent Fiber Content on Intake, Digestibility, and Chewing Activity in Fattening Heifer Fed Total Mixed Ration.

The objective of this study was to determine the effects of physically effective neutral detergent fiber (peNDF) content in total mixed ration (TMR) on dry matter intake, digestibility, and chewing activity in fattening Hanwoo (Bos taurus coreanae) heifers. The experiment was designed as a replicated 3×3 Latin square using 12 heifers. Fattening heifers were offered one of three diets [high (T1), medium (T2), and low (T3) peNDF] obtained by different mixing times (3, 10, and 25 min) for the same TMR feed. The peNDF content of TMR was determined by multiplying the proportion of dry matter retained by a 1.18 mm-screen in a Penn State Particle Separator by the dietary NDF content. The peNDF1.18 content was 30.36%, 29.20%, and 27.50% for the T1, T2, and T3 diets, respectively (p<0.05). Dry matter intake was not affected by peNDF content in TMR. Total weight gain in T1 group was significantly higher (p<0.05) than in T2 and T3 groups. However, weight gain did not differ between T2 and T3 groups. The feed conversion ratio decreased with an increase in the peNDF content (T1: 12.18, T2: 14.17, and T3: 14.01 g/g). An increase in the peNDF content of TMR was associated with a linear increase in the digestibility of dry matter, crude protein, crude fiber, neutral detergent fiber, and acid detergent fiber (p<0.05). Also, an increase in peNDF content of the TMR resulted in a linear increase in the number of chews in eating and ruminating (p<0.05), and consequently in the number of total chews (p<0.05). These results indicate that peNDF content affects digestibility and chewing activity. Consequently, the peNDF content of TMR should be considered for improving feed efficiency, digestibility, body weight gain, and performance in fattening heifers.

Brain Reward Circuits in Morphine Addiction.

Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.

Pathophysiological Role of Neuroinflammation in Neurodegenerative Diseases and Psychiatric Disorders.

Brain diseases and disorders such as Alzheimer disease, Parkinson disease, depression, schizophrenia, autism, and addiction lead to reduced quality of daily life through abnormal thoughts, perceptions, emotional states, and behavior. While the underlying mechanisms remain poorly understood, human and animal studies have supported a role of neuroinflammation in the etiology of these diseases. In the central nervous system, an increased inflammatory response is capable of activating microglial cells, leading to the release of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. In turn, the pro-inflammatory cytokines aggravate and propagate neuroinflammation, degenerating healthy neurons and impairing brain functions. Therefore, activated microglia may play a key role in neuroinflammatory processes contributing to the pathogenesis of psychiatric disorders and neurodegeneration.

Regulation of C6 glioma cell migration by thymol.

Tumor cell motility exhibits a crucial role in tumor development. Therefore, the present study aimed to investigate whether thymol could reduce C6 glioma cell migration. Cell viability was determined using the EZ-Cytox Cell Viability kit. The scratch wound healing and Boyden chamber assays were performed to test C6 glioma cell migration in the presence of fetal bovine serum (FBS). Additionally, the study investigated whether signaling proteins relevant to C6 glioma cell migration, i.e., extracellular signal-regulated kinases (ERK)1/2, protein kinase Cα (PKCα), matrix metallopeptidase (MMP)9 and MMP2, were affected by thymol treatment. Up to 30 µM, thymol did not alter cell viability, whereas 100 µM thymol induced the death of ~20% of the cells. Furthermore, thymol (30 µM) significantly reduced FBS-induced migration. In the FBS-stimulated C6 glioma cells, thymol (30 µM) suppressed PKCα and ERK1/2 phosphorylation. MMP9 and MMP2 production was also significantly reduced by treatment with 30 µM thymol in the C6 glioma cells. Taken together, these results indicate that thymol attenuates C6 glioma cell migration. Additionally, the study suggests that the effect of thymol on the FBS-induced migration of C6 glioma cells affects PKCα and ERK1/2 signaling, and suppresses MMP9 and MMP2 production.

Protective Effect of Areca catechu Leaf Ethanol Extract Against Ethanol-Induced Gastric Ulcers in ICR Mice.

Gastric ulcer is a common digestive disorder that results in considerable suffering. Hence, this digestive pathology has been the focus of a number of recent studies. Although numerous drugs have been developed to treat gastric ulcers, therapeutic approaches for many of the complications associated with these drugs remain to be identified. For this reason, many natural compounds have been explored as alternatives for these drugs. In this study, we have investigated the effectiveness of Areca catechu leaf ethanol extract (ACE) for treating ethanol-induced gastric ulcers in mice. We performed histological as well as immunohistochemical examinations to explore the therapeutic properties of ACE. We also examined the levels of inflammatory signaling molecules to confirm the anti-inflammatory effects of ACE. The histochemical data demonstrate that ACE can protect the mucosal epithelium as well as the vascular supply in the gastric tract. Furthermore, ACE significantly reduced the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 receptor (IL-6R), inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and nuclear factor-kappa B (NF-κB). Taken together, these data suggest that ACE administration may have the potential as an alternative treatment for gastric ulcer because of its cytoprotective and anti-inflammatory effects and ability to promote the rejuvenation and revascularization of the damaged gastric epithelium.

Piperine inhibits platelet-derived growth factor-BB-induced proliferation and migration in vascular smooth muscle cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood vessels are important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Piperine, a major component of black pepper, has antioxidant, anticancer, and anti-inflammatory activity. However, the antiatherosclerotic effects of piperine have not been investigated. In this study, the effects of piperine on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs were investigated. The antiproliferative effects of piperine were determined using MTT assays, cell counting, real-time polymerase chain reaction, and western blots. Our results showed that piperine significantly attenuated the proliferation of VSMCs by increasing the expression of p27(kip1), regulating the mRNA expression of cell cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration-dependent manner (30-100 µM). Moreover, we examined the effects of piperine on the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber assay, H2DCFDA staining, and western blots. Our results showed that 100 µM piperine decreased cell migration, the production of reactive oxygen species (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Taken together, our results suggest that piperine inhibits PDGF-BB-induced proliferation and the migration of VSMCs by inducing cell cycle arrest and suppressing MAPK phosphorylation and ROS. These findings suggest that piperine may be beneficial for the treatment of vascular-related disorders and diseases.

Artemisinin attenuates platelet-derived growth factor BB-induced migration of vascular smooth muscle cells.

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through H2DCF-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT (10 µM and 30 µM) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT (10 µM and 30 µM) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells.

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, 400 µg/mL) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.