Sword Bean (Canavalia gladiata) Pods Induce Differentiation in MC3T3-E1 Osteoblast Cells by Activating the BMP2/SMAD/RUNX2 Pathway.

Sword bean (SB) contains various phytochemicals, such as flavonoids, tannins, saponins, and terpenoids. Although the evaluation of its potential functions, including antioxidant, anti-obesity, anti-inflammatory, liver protection, and antiangiogenic activities, has been widely reported, research on their use in osteoporosis prevention is insufficient. Furthermore, while various studies are conducted on SB, research on sword bean pods (SBP) is not yet active, and little is known about it. Therefore, this study investigated the effects of promoting osteoblast differentiation of MC3T3-E1 cells using SB and SBP extracts and their mechanisms. We show that SBP extracts increase osteoblast proliferation, mineralization-activated alkaline phosphatase (ALP), and collagen synthesis activities. Additionally, treatment with SBP extract increased the expression of markers related to osteoblast differentiation, such as ALP, SPARC, RUNX2, COL-I, BMP2, OCN, and OPN. It was confirmed that SBP induces differentiation by activating the BMP2/SMAD/RUNX2 pathway. We also show that SBP is more effective than SB, and SBP may be useful in assimilating bone minerals and preventing osteoporosis.

Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders.

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood-brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer's disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson's disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research.

Hepatoprotective Effects of Radish (Raphanus sativus L.) on Acetaminophen-Induced Liver Damage via Inhibiting Oxidative Stress and Apoptosis.

Alcohol and drug overdoses cause liver diseases such as cirrhosis, hepatitis, and liver cancer globally. In particular, an overdose of acetaminophen (APAP), which is generally used as an analgesic and antipyretic agent, is a major cause of acute hepatitis, and cases of APAP-induced liver damage are steadily increasing. Potential antioxidants may inhibit the generation of free radicals and prevent drug-induced liver damage. Among plant-derived natural materials, radishes (RJ) and turnips (RG) have anti-inflammatory, anticancer, and antioxidant properties due to the presence of functional ingredients, such as glucosinolate and isothiocyanate. Although various functions have been reported, in vivo studies on the antioxidant activity of radishes are insufficient. Therefore, we aim to evaluate the hepatoprotective effects of RG and RJ in APAP-induced liver-damaged mice. RG and RJ extracts markedly improved the histological status, such as inflammation and infiltration, of mice liver tissue, significantly decreased the levels of alanine transaminase, aspartate aminotransferase, and malondialdehyde, and significantly increased the levels of glutathione, superoxide dismutase and catalase in the APAP-induced liver-damaged mice. In addition, RG and RJ extracts significantly increased the expression of Nrf-2 and HO-1, which are antioxidative-related factors, and regulated the BAX and BCL-2, thereby showing anti-apoptosis activity. These results indicated that RG and RJ extracts protected mice against acute liver injury, attributed to a reduction in both oxidative stress and apoptosis. These findings have clinical implications for the use of RG and RJ extracts as potential natural candidates for developing hepatoprotective agents.

Regioselective Synthesis of 6-O-Acetyl Dieckol and Its Selective Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

Dieckol, a phlorotannin from Ecklonia cava, has shown potential for use as an anticancer agent that selectively kills cancer cells. However, it is necessary to amplify its potency without damaging its inherent safety in order to develop it as a competitive chemotherapeutic. Here, we explored the controlled O-acylations of dieckol. Acyl groups could be consistently introduced to the 6-O position of dieckol with a high regioselectivity, which was confirmed by NOESY, HMBC and HSQC spectroscopies. In cytotoxicity studies on the newly synthesized 6-O-acetyl, 6-O-benzoyl dieckols and previously synthesized 6-O-alkyl dieckols against A549 vs. normal cells, all of the derivatives showed low cytotoxicity in normal cells with an IC50 of 481-719 µM, and highly structure-dependent cytotoxicity in A549 cells with an IC50 of 7.02 (acetyl)-842.26 (benzyl) µM. The selectivity index also showed a large structure dependency in the range of 0.67 (benzyl)-68.58 (acetyl). An analysis of the structure-activity relationship indicated that the activity was dramatically reduced in the presence of a benzene ring and was highly increased in the presence of small polar substituents. Conclusions: Controlled mono-O-modifications of dieckol could be a powerful tool to enhance the anticancer activity of dieckol, thus contributing to the development strategy for dieckol-based chemotherapeutics.

Sword Bean (Canavalia gladiata) Pod Exerts Anti-Allergic and Anti-Inflammatory Effects through Modulation of Th1/Th2 Cell Differentiation.

Allergy is an immunoglobulin E (IgE)-mediated process, and its incidence and prevalence have increased worldwide in recent years. Therapeutic agents for allergic diseases are continuously being developed, but side effects follow when used for a long-term use. Therefore, treatments based on natural products that are safe for the body are urgently required. Sword bean (Canavalia gladiata) pod (SBP) has been traditionally used to treat inflammatory diseases, but there is still no scientific basis for its anti-allergic effect. Accordingly, this study investigates the anti-allergic effect and its mechanism of SBP in vitro and in vivo. SBP reduced the nitric oxide production and decreased mRNA and protein expression of inflammatory mediates (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and inhibited the phosphorylation of nuclear factor kappa B (NF-κB), a major signaling molecule in the inflammatory response. Additionally, SBP extract treatment inhibited phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling activity to further inhibit degranulation and allergy mediator generation and control the balance of Th1/Th2 cells, which can induce an allergic reaction when disrupted. Furthermore, the SBP extract exhibited anti-allergic effects in anti-dinitrophenyl IgE-induced RBL-2H3 cells and ovalbumin-treated mice. These findings have potential clinical implications for the treatment as well as prevention of allergic diseases.

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells.

The intestinal epithelial barrier is the primary and most significant defense barrier against ingested toxins and pathogenic bacteria. When the intestinal epithelium barrier is breached, inflammatory response is triggered. GWAS data showed that endoplasmic reticulum (ER) stress markers are elevated in Inflammatory Bowel Disease (IBD) patients, which suggests ER stress regulation might alleviate IBD symptoms. Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties, although it is unclear whether FA has these effects on the intestine. Therefore, we investigated the effect of FA in vitro and in vivo. It was found that FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells, indicating that the ER stress pathway was implicated in its anti-inflammatory activities. The permeability of polarized Caco-2 cells in the presence and absence of proinflammatory cytokines were decreased by FA, and MUC2 mRNA was overexpressed in the intestines of mice fed a high-fat diet (HFD) supplemented with FA. These results suggest that FA has a protective effect on intestinal tight junctions. In addition, mouse intestine organoids proliferated significantly more in the presence of FA. Our findings shed light on the molecular mechanism responsible for the antioxidant effects of FA and its protective benefits on the health of the digestive system.

Immature sword bean pods (Canavalia gladiata) inhibit adipogenesis in C3H10T1/2 cells and mice with high-fat diet-induced obesity.

BACKGROUND: Sword bean (SB; Canavalia gladiata) is a perennial vine used as a food and medicinal plant in Asia. SB is rich in nutrients, such as flavonoids and urease, and has various functions, including beneficial effects on dysentery, nausea, and hemorrhoids, as well as anti-inflammatory and antioxidant activity. Various plant parts are used; however, little is known about the physiological effects of SB pods (SBP). In this study, the anti-obesity effects of SBP extract were evaluated. METHODS: To investigate the anti-obesity effects of SBP extract, we confirmed the SBP extract downregulated lipogenesis-related genes and upregulated genes involved in lipolysis and brown adipocyte markers in differentiated C3H10T1/2 adipocytes in vitro. Next, we use a high-fat diet (HFD)-induced obesity mouse model to determine the anti-obesity effects of SBP extract. RESULTS: Treatment with SBP extract significantly reduced adipocytes. The extract decreased the HFD-induced increases in body weight and plasma triglyceride levels in mice after 8 weeks. mRNA and protein levels of the adipogenesis and lipogenesis-related factors CCAAT/enhancer binding protein-ß, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ (PPARγ), and their target genes Ap2, SREBP-1c, FAS, and SCD-1 were reduced by SBP extract. In contrast, AMP-activated protein kinase and sirtuin1, involved in the thermogenic catabolism of fat, were activated by SBP extract in adipocytes and white adipose tissue, increasing the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, peroxisome proliferator-activated receptor-α (PPARα), and uncoupling protein 1 and activating thermogenic activity. CONCLUSION: SBP extract exerts an anti-obesity effect by inhibiting lipogenesis-related factors and activating fat-catabolizing factors; it is, therefore, a promising functional food and natural anti-obesity agent.

Identification for antitumor effects of tramadol in a xenograft mouse model using orthotopic breast cancer cells.

In our previous research showed that tramadol having potential anti-tumor effect was associated with enhancement of oncological prognosis in patients with breast cancer surgery. As these effects have not been confirmed by clinical dose-regulated animal or prospective human studies, we investigated the anti-tumor effect of tramadol in vivo. Female nude mice orthotopically inoculated with luciferase-expressing MCF-7 cells, were randomly divided into the control (saline), tramadol group 1 (1.5 mg kg-1 day-1), tramadol group 2 (3 mg kg-1 day-1), and morphine (0.5 mg kg-1 day-1) (n = 5/group). Bioluminescence signals after D-luciferin injection, tumor size, and tumor weight were compared among groups after 4 weeks. Estrogen receptor (ER), progesterone receptor (PR), and transient receptor potential vanilloid (TRPV)-1 expression, natural killer (NK) cell activity, and serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 were then examined. Tumour growth was attenuated in tramadol-treated groups (P < 0.05). NK cell activity was significantly decreased only in the morphine treated group not in sham, control, and tramadol groups. The expression levels of ERα, PRα and ß, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group. Serum levels of IL-6 and TNFα were reduced in both tramadol-treated group 1 and 2 compared to the control group. Overall, clinical dose of tramadol has anti-tumour effects on MCF-7 cell-derived breast cancer in a xenograft mouse model.

Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study.

BACKGROUND: The surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model. METHODS: The effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery. RESULTS: Dexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P<0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P<0.001) and the in vivo imaging system (P=0.03). CONCLUSIONS: Dexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.

Fermentation of Chestnut (Catanea crenata Sieb) Inner Shell Enhances Anti-Obesity Effects in 3T3-L1 and C3H10T1/2 Adipocytes.

Chestnut inner shell (CIS) is rich in phenols and flavonoids such as gallic acid and ellagic acid, which are known to exhibit effective antioxidant and anti-obesity properties. Fermentation using lactic acid bacteria can enhance the physiological activity by increasing the contents of such functional ingredients. In this study, we evaluated the anti-obesity effects of a CIS extract subjected to a fermentation process (fermented CIS [FCIS]). Treatment with CIS and FCIS extracts (125, 250, and 500 µg/mL) increased cell viability and did not induce apoptosis, indicating no toxicity. The extract suppressed the gene expression of adipogenic factors, peroxisome proliferation-activated receptor gamma, CCAAT/enhancer binding protein (C/EBP) alpha, and C/EBP beta (by 7.75% and 67.59%, 21.41% and 66.27% in 500 µg/mL, respectively), and consequently suppressed the expression of downstream lipogenic factors such as fatty acid synthase, stearoyl CoA desaturase-1, citrate synthase, and ATP citrate lyase. The expression of factors involved in fat catabolism and ß-oxidation increased in a dose-dependent manner, thereby preventing fat accumulation. This observation was consistent with the significant decrease in the staining intensity for lipid droplets, which indicated that lipid accumulation was decreased by 15.46% and 29.44% in 3T3L-1 and 27.01% and 46.68% in C3H10T1/2. Together, these results demonstrate the higher anti-obesity effects of FCIS extract than that of CIS extract, indicating the potential applicability of FCIS as an effective natural raw material to curb obesity.

Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway.

The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

Antioxidant Effect of Lycium barbarum Leaf through Inflammatory and Endoplasmic Reticulum Stress Mechanism.

Although the prevalence and incidence of inflammatory bowel disease (IBD), a defective immune response of the gastrointestinal tract, has been increasing in North America and Western Europe, recent studies have shown that this disease is also increasing rapidly in Asia. Several studies have been searching for functional foods that can prevent or reduce IBD symptoms because the drug treatments for IBD are expensive with complications. Genome-Wide Association Study (GWAS), an observational study of a genome-wide set of genetic variants in different individuals, showed that endoplasmic reticulum (ER) stress is one of the causes of IBD. Previously, we reported the effects of Lyciumbarbarum fruit and this study investigated the effects of Lycium barbarum leaf (LL) on inflammation and ER stress of the intestine. The paracellular permeability, antioxidant, and anti-inflammatory response were measured on polarized Caco-2 cells. The ER stress pathway and pro-inflammatory cytokines were evaluated on MEF-knockout cell lines, and on the intestines of the mice fed a high-fat diet with lipopolysaccharide-induced inflammation. Our data showed that the LL pretreatment strengthened the tight junction integrity and reduced NO production both in the presence and in the absence of inflammation. Furthermore, LL inhibited ER stress and inflammation via IRE1α and XBP1 in vitro as well as in the inflamed intestines of mice, highlighting the antioxidant and anti-inflammatory function of LL in an IRE1α-XBP1-dependent manner.

Mustard Leaf Extract Suppresses Psychological Stress in Chronic Restraint Stress-Subjected Mice by Regulation of Stress Hormone, Neurotransmitters, and Apoptosis.

Mustard leaf (Brassica juncea var. crispifolia L. H. Bailey) has been reported to have psychological properties such as anti-depressant activities. However, studies on chronic stress and depression caused by restraint have not been conducted. Therefore, this study aimed to evaluate the effects of a mustard leaf (ML) extract on chronic restraint stress (CRS) in mice. Male mice were subjected to a CRS protocol for a period of four weeks to induce stress. The results showed that the ML extract (100 and 500 mg/kg/perorally administered for four weeks) significantly decreased corticosterone levels and increased neurotransmitters levels in stressed mice. Apoptosis by CRS exposure was induced by Bcl-2 and Bax expression regulation and was suppressed by reducing caspase-3 and poly (ADP-ribose) polymerase expression after treatment with the ML extract. Our results confirmed that apoptosis was regulated by increased expression of brain-derived neurotrophic factor (BDNF). Additionally, cytokine levels were regulated by the ML extract. In conclusion, our results showed that the ML extract relieved stress effects by regulating hormones and neurotransmitters in CRS mice, BDNF expression, and apoptosis in the brain. Thus, it can be suggested that the studied ML extract is an agonist that can help relieve stress and depression.

Anti-Inflammatory Effect of Immature Sword Bean Pod (Canavalia gladiata) in Lipopolysaccharide-Induced RAW264.7 Cells.

Sword bean has been known as a traditional medicinal plant to treat cancer, sinus infection, and suppurative disease. It also possesses hypertension-relieving, antioxidation, and antibacterial effects. However, studies on the efficacy of sword bean are limited to mature beans. Few studies have focused on immature sword bean pod (ISBP). Therefore, this study aimed to investigate the anti-inflammatory effect of ISBP in RAW264.7 cells stimulated with lipopolysaccharide (LPS). After LPS-induced RAW264.7 cells were treated with ISBP at concentrations (0.5, 1, 2, and 5 mg/mL), levels of nitrite oxide (NO) and prostaglandin E2 (PGE2) production, protein, and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), inflammatory cytokine secretion level, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity were determined. Under inflammatory conditions induced by LPS, ISBP reduced levels of inflammatory mediators NO and PGE2 by 60% and 23%, respectively. It also decreased protein and mRNA expression levels of iNOS and COX-2 known to synthesize inflammatory mediators. Inflammatory cytokines, interleukin (IL)-6, and IL-1ß, levels were decreased, while interferon gamma level was increased by ISBP based on enzyme-linked immunosorbent assay (ELISA) and real time-polymerase chain reaction results. Finally, ISBP showed the ability to inhibit NF-κB activity. In conclusion, ISBP can alleviate inflammation by controlling inflammation-related substances, and may have efficacy as a healthful functional food and natural anti-inflammatory drug.

Platycodon grandiflorum Extract Reduces High-Fat Diet-Induced Obesity Through Regulation of Adipogenesis and Lipogenesis Pathways in Mice.

Obesity is caused by an energy imbalance between food intake and energy expenditure, and has detrimental effects on human health. Platycodon (Platycodon grandiflorum) widely grows in Korea, Japan, and China. It has long been used for food and as a medicinal product. However, the mechanism of the improvement of obesity by platycodon was still not clear. Therefore, we investigated the detailed mechanisms of the antiobesity activity of platycodon extracts. Twenty mice (C57BL/6J) were placed into five groups. The test group received 1 g/kg platycodon extracts. The positive control group received 10 mg/kg orlistat, while the negative control and normal control groups received phosphate-buffered saline. The extracts were given orally daily for 8 weeks. The in vivo treatment of platycodon extracts reduced body weight gain by 7.5%, improved plasma lipid profiles. In the groups given platycodon extracts, leptin was significantly decreased whereas adiponectin was increased. Furthermore, platycodon extracts downregulated lipogenic gene (e.g., lipoprotein lipase, acetyl-CoA carboxylase, and fatty acid synthase) expression and increased lipolysis genes (e.g., carnitine palmitoyltransferase 1α, hormone-sensitive lipase, and uncoupling proteins 2) in liver and white adipose tissue. In addition, platycodon extracts inhibited the expression of key adipogenic transcriptional factors. In conclusion, we have demonstrated that platycodon extracts ameliorate high-fat diet-induced obesity and its related metabolic disease by regulating multiple pathways. Dietary supplementation of platycodon extracts as a functional food and medicinal ingredients may be suitable for prevention and treatment of obesity.

Anti-inflammatory effect of aerial bulblets of Dioscorea japonica Thunb extract through inhibition of NF-κB and MAPK signalling pathway in RAW 264.7.

BACKGROUND: Yam (Dioscorea japonica Thunb) is a well-known health food in Korea and is widely distributed in the temperate and tropical regions. Although various medical effects of yam have been demonstrated, there is little current knowledge on the efficacy of Youngyeoja (YYJ; the aerial bulblets of the yam plant), their physiological effects, and their mechanism of action. METHODS: To investigate the anti-inflammatory effects of YYJ, we examined the level of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells treated with YYJ extract. Nitric oxide (NO) and prostaglandin E2 (PGE2) levels were determined using enzyme-linked immunosorbent assays. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated using real-time polymerase chain reaction and western blotting. In addition, activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) was detected using western blotting. RESULTS: Treatment of macrophages with LPS markedly induced the production of NO and PGE2. YYJ treatment inhibited the induction of inflammatory mediators and the expression of iNOS and COX-2. More importantly, LPS-induced phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) was suppressed by treatment with YYJ, suggesting YYJ inhibited NF-κB activation. Furthermore, YYJ inhibited the LPS-induced phosphorylation of MAPKs. CONCLUSION: YYJ was shown to have a potent anti-inflammatory effect in LPS-stimulated RAW 264.7 cells, which may be attributed to its inhibitory effect on NF-κB and MAPK activation, consequently blocking the production of inflammatory factors. Therefore, these results suggest that the YYJ extracts could be used as anti-inflammatory agents.

Anti-inflammatory effect of Lycium barbarum on polarized human intestinal epithelial cells.

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5-50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.

Immobilization of phenol-containing molecules on self-assembled monolayers on gold via surface chemistry.

Various phenol-containing molecules such as flavonoids have a wide range of biological effects including anticancer, antimicrobial, and anti-inflammatory properties, and, therefore, they have become subjects of active research for various medicinal and biological applications. To construct applicable materials incorporated with phenol-containing molecules, strategies for immobilization of phenol-containing molecules on solid substrates are required. Although several immobilization methods have been devised and reported, mostly harnessing phenol functionality, however, development of a general immobilization method has been hampered due to its complicated chemical reactions and low reaction yields on surfaces. Furthermore, the use of phenol as a reaction center may compromise the biological activity of phenol-containing molecules. Here, we describe a simple, fast, and reliable method for the surface immobilization of phenol-containing molecules by introducing chemical functional groups, carboxylic acid, thiol, and azide, while maintaining phenol functionality by way of the Mannich-type condensation reaction. We examined the chemical functionalization of naphthol, tyrosine, and flavanone and their immobilization to the self-assembled monolayers on gold via various surface chemistries: the carbodiimide coupling reaction, Michael addition, and the 'click' reaction. We strongly believe our method can be a general and practical platform for immobilization of various phenol-containing molecules on surfaces of various materials.

Dexmedetomidine restores autophagy and cardiac dysfunction in rats with streptozotocin-induced diabetes mellitus.

AIMS: Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor agonist, has anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects in diabetes mellitus (DM) rats. The underlying molecular mechanisms and signaling pathways of diabetic cardiomyopathy remain poorly understood. This study aimed to elucidate the effect of DEX on cardiac function in DM rats. METHODS: Eight-week-old male Sprague Dawley rats were divided into three groups: control (n = 5), diabetes (DM, n = 7), and diabetes + DEX (DM + DEX, n = 10). DM was induced via intraperitoneal injection of streptozotocin (70 mg/kg); at 3 days later, DEX (1 µg/kg/h) was administered for 4 weeks. Cardiac function was evaluated using pressure-volume loop analysis and echocardiography. Left ventricular (LV) histological sections were used to analyze the interstitial collagen fraction. Using the LV samples, we performed a western blot analysis to evaluate signaling pathways and autophagic markers. RESULTS: The DM group had lower body weight and higher blood glucose level and heart weight/body weight ratio than the control group. However, metabolic changes did not differ between the DM and DM + DEX groups. Pressure-volume loop analysis and echocardiography showed impaired cardiac function, evidenced by a decrease in systolic and diastolic function, in both DM groups. DEX treatment in DM rats was associated with increased LV end-systolic pressure, LV contractility, cardiac output, and relaxed LV function compared with that in non-treated DM rats. LC3B and autophagy-related gene (ATG) proteins increased in the hearts of DM rats compared with the hearts of control rats. However, DEX reduced the expression of LC3B and ATG proteins in the hearts of DM rats. Increased p-ERK and decreased p-AKT were reduced in the hearts of DEX-treated DM rats. CONCLUSIONS: DEX reduces cardiac dysfunction and impaired autophagy in DM rats. This study reinforces our understanding of the potential anti-autophagic effect of DEX in patients with diabetic cardiomyopathy.

Monodisperse Magnetic Silica Hexapods.

A simple yet versatile solution-based process to produce colloidal silica hexapods is developed in which various shapes of silica rods are grown on the faces of cubes in a controlled manner. In the presence of hematite cubic particles, water droplets nucleate on the surface of hematite by phase separation in pentanol. By adjusting the water concentration, six droplets can form on each face of the hematite cube. A silica precursor is then administered into the system, which gradually diffuses into the water droplets through the oil phase. Within the droplets, hydrolysis and condensation of the precursors take place, leading to formation of silica rods. As a result, silica hexapods on a magnetic hematite cubic seed are produced. Furthermore, when the emulsions are aged at 60 °C prior to the silica growth, the water content in the solution decreases gradually due to evaporation and spiky sharp hexapods are produced. On the other hand, when organosilane precursor is added, pancake-like hexapods are formed due to the reduction of interfacial tension. These colloidal hexapods can further be utilized as new building blocks for self-assembly to construct functional materials or as a model system to understand collective behaviors.