Predictive Guide for Collective CO2 Adsorption Properties of Mg-Al Mixed Oxides.

Although solid adsorption processes offer attractive benefits, such as reduced energy demands and penalties compared with liquid absorption processes, there are still pressing needs for solid adsorbents with high adsorption capacities, thermal efficiencies, and energy-intensive regeneration in gas-treatment processes. The CO2 adsorption capacities of layered double oxides (LDOs), which are attractive solid adsorbents, have an asymmetric volcano-type correlation with their relative crystallinities. Furthermore, new collective adsorption properties (adsorption capacity, adsorptive energy and charge-transfer amount based on the adsorbent weight) are proposed based on density functional theory (DFT) calculations and measured surface areas. The correlation of these collective properties with their crystallinities is in good agreement with the experimentally measured CO2 adsorptive capacity trend, providing a predictive guide for the development of solid adsorbents for gas-adsorption processes.

Zerumbone suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1ß is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1ß-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1ß-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1ß treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1ß-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1ß-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats.

BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS AND FINDINGS: LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls. CONCLUSIONS: Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Serum cholesterol concentration and prevalence, awareness, treatment, and control of high low-density lipoprotein cholesterol in the Korea National Health and Nutrition Examination Surveys 2008-2010: Beyond the Tip of the Iceberg.

BACKGROUND: The mortality rate from cardiovascular disease (CVD) among young adults has declined less than that in the older population, raising concerns about the increasing prevalence of obesity-related conditions including hypercholesterolemia in the younger population. We investigated the age-standardized mean levels of serum cholesterols and the prevalence, awareness, treatment and control rates of hyper-low-density lipoprotein (LDL)-cholesterolemia based on age. METHODS AND RESULTS: Nationally representative samples of 19 489 subjects aged ≥20 years were analyzed from the Korea National Health and Nutrition Examination Surveys 2008-2010. Hyper-LDL-cholesterolemia was individually evaluated by the 2004 National Cholesterol Education Program Adult Treatment Panel III guidelines. Age-standardized mean levels of total cholesterol, high-density lipoprotein-cholesterol, LDL-cholesterol, and triglycerides were 186.8, 48.0, 112.9, and 136.0 mg/dL, respectively. Age-standardized prevalence of hyper-LDL-cholesterolemia was 23.2% (men, 25.5%; women, 21.8%). Among subjects with hyper-LDL-cholesterolemia, awareness and treatment rates were significantly lower in younger adults (<50 years) compared to older adults ≥50 years (awareness, 8.0% versus 21.5%; treatment, 5.1% versus 18.5%, all Ps<0.001), indicating significant discrepancies in awareness and treatment rates of hypercholesterolemia between younger and older adults. Among subjects aware of their hyper-LDL-cholesterolemia, younger adults were more likely to have controlled LDL-cholesterol than the elderly (82.1% versus 67.5%, P<0.001). CONCLUSIONS: Compared to the elderly, significant proportions of young and middle-aged adults are unaware of their hypercholesterolemia and are not treated with proper lipid-lowering medications. Early screening, education, and proper management should be stressed in national public healthcare policies to reduce the increasing burden of CVD in the younger population with undiagnosed hypercholesterolemia.

Therapeutic effects of water soluble danshen extracts on atherosclerosis.

Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE. To evaluate the effects of DE in vivo, carotid balloon injury and tail vein thrombosis were induced in Sprague-Dawley (SD) rats and iliac artery stent was induced in New Zealand white rabbits. The inhibitory action of DE on platelet aggregation was confirmed with an impedance aggregometer. DE inhibited the production of reactive oxygen species, and the migration and proliferation of platelet-derived growth factor-BB stimulated VSMCs. Furthermore, DE prevented inflammation and apoptosis in HUVECs. Both effects of DE were reconfirmed in both rat models. DE treatment attenuated platelet aggregation in both in vivo and ex vivo conditions. Pretreatment with DE prevented tail vein thrombosis, which is normally induced by κ-carrageenan injection. Lastly, DE-treated rabbits showed decreased in-stent restenosis of stented iliac arteries. These results suggest that water soluble DE modulates key atherogenic events in VSMCs, endothelial cells, and platelets in both in vitro and in vivo conditions.

Korean red ginseng (Panax ginseng) improves insulin sensitivity in high fat fed Sprague-Dawley rats.

Many studies have documented that ginseng has antidiabetic and antiobesity effects, but the mechanism of the effects has not been elucidated. The aim of this study was to determine the effect of Korean red ginseng (KRG, Panax ginseng) and investigate the mechanism of antidiabetic and antiobesity effects in obese insulin resistant animal models. Sprague-Dawley (SD) rats were divided into three groups: a control group (group I) fed a normal diet, another group (group II) fed only high fat diet (HFD) and a third group (group III) fed HFD with KRG (200 mg/kg, oral) for 18 weeks. The body weight, food intake, adipose tissues, liver, kidney, pancreas, adiponectin, and leptin were measured. Blood glucose, insulin tolerance test, and hyperinsulinemic euglycemic clamp test were investigated. A significant weight reduction, especially fat mass reduction, was observed in the KRG treated group. Increased insulin sensitivity was found in the KRG treated group. We observed increased insulin signalling, increased phosphorylation of IR, IRS-1, Akt, and membranous GLUT4 in muscle by Western blotting assay. In conclusion, KRG may have antidiabetic and antiobesity effects due to partly increased insulin sensitivity by increased adipokine and partly enhanced insulin signalling.

Combination of paclitaxel- and retinoic acid-incorporated nanoparticles for the treatment of CT-26 colon carcinoma.

The aim of this study was to evaluate the antitumor effect of combinatorial targeted therapy with paclitaxel and all-trans retinoic acid (ATRA) nanoparticles in vitro. Paclitaxel-incorporated pullulan acetate (PA) nanoparticles were prepared by the nanoprecipitation-solvent evaporation method. ATRA-incorporated nanoparticles were prepared by dialysis using a methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) copolymer. Particle sizes of paclitaxel-incorporated nanoparticles and ATRA-incorporated nanoparticles were about 160 nm and 60 nm, respectively. Nanoparticles were reconstituted in various aqueous media such as deionized water, phosphate-buffered saline, and fetal bovine serum-supplemented cell culture media. The combination of paclitaxel + ATRA (10 + 10 µg/mL) delivered by nanoparticles showed a synergistic antiproliferative effect against CT26 cells that was not observed with other combinations. Furthermore, the activity of MMP-2, a key enzyme in tumor cell invasion, was significantly decreased in cells treated with the combination of paclitaxel and ATRA while other combinations and single agents did not significantly affect its activity. A matrigel assay supported these results, indicating that paclitaxel/ATRA combination nanoparticles are effective for the inhibition of the invasion of tumor cells. The results of the present study suggest that combination treatment with paclitaxel and ATRA could be an effective treatment for the inhibition of tumor cell proliferation and invasion, and that nanoparticles are promising candidates for antitumor drug delivery.

Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats.

Magnesium lithospermate B (MLB) is one of the major active components of Salvia miltiorrhizae. The anti-oxidative effects of Salvia miltiorrhizae have been previously reported. The aim of this study was to investigate the effect of purified MLB on hepatic fibrosis in rats and on the fibrogenic responses in hepatic stellate cells (HSCs). Hepatic fibrosis was induced in rats by intraperitoneal thioacetamide (TAA) injections over a period of 8 or 12 weeks. MLB was orally administered daily by gavage tube. Serum AST and ALT levels in TAA+ MLB group were significantly lower than those in TAA only group at week 8. Hepatic fibrosis was significantly attenuated in TAA+MLB group than in TAA only group at week 8 or 12. Activation of HSCs was also decreased in TAA+MLB group as compared to TAA only group. Hepatic mRNA expression of α-smooth muscle actin (α-SMA), TGF-ß1, and collagen α1(I) was significantly decreased in TAA+MLB group as compared to TAA only group. Incubation with HSCs and MLB (>or=100 µM) for up to 48 h showed no cytotoxicity. MLB suppressed PDGF-induced HSC proliferation. MLB inhibited NF-ΚB transcriptional activation and monocyte chemotactic protein 1 (MCP-1) production in HSCs. MLB strongly suppressed H(2)O(2)-induced reactive oxygen species (ROS) generation in HSCs, and MLB inhibited type I collagen secretion in HSCs. We concluded that MLB has potent antifibrotic effect in TAA-treated cirrhotic rats, and inhibits fibrogenic responses in HSCs. These data suggest that MLB has potential as a novel therapy for hepatic fibrosis.

Dietary monounsaturated fatty acids but not saturated fatty acids preserve the insulin signaling pathway via IRS-1/PI3K in rat skeletal muscle.

Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) show different effects on the development of insulin resistance. In this study, we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model. Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly divided into three groups and fed one of the following diets for 3 weeks; a normal chow diet, an SFA (lard oil) enriched or a MUFA (olive oil) enriched high-fat diet. The vastus lateralis muscle was used for analyses. Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet, as compared to those fed the SFA diet (p < 0.001). The SFA diet reduced IRS-1 expression and phosphorylated PI3K levels in skeletal muscle, as compared with a chow diet (p < 0.001, respectively). On the contrary, muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet (p < 0.001, respectively). Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet, as compared to those fed a chow diet (p < 0.001). These changes in insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet. In conclusion, the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3K insulin signaling pathway which was altered by dietary SFA.

Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction.

AIMS: We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus. METHODS AND RESULTS: The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of alpha-lipoic acid (alphaLA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant alphaLA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia. CONCLUSION: MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications.

Protective effects of magnesium lithospermate B against diabetic atherosclerosis via Nrf2-ARE-NQO1 transcriptional pathway.

Hyperglycemia-induced oxidative stress is known to play an important role in the development of several diabetic complications, including atherosclerosis. Although a number of antioxidants are available, none have been found to be suitable for regulating the oxidative stress response and enhancing antioxidative defense mechanisms. In this study, we evaluated the effects of magnesium lithospermate B (LAB) against oxidative stress. We also endeavored to identify the target molecule of LAB in vascular smooth muscle cells (VSMCs) and the underlying biochemical pathways related to diabetic atherosclerosis. Modified MTT and transwell assays showed that the increased proliferation and migration of rat aortic VSMCs in culture with high glucose was significantly inhibited by LAB. LAB also attenuated neointimal hyperplasia after balloon catheter injury in diabetic rat carotid arteries. To determine molecular targets of LAB, we studied the effects of LAB on aldose reductase (AR) activity, O-GlcNAcylation, and protein kinase C (PKC) activity in VSMCs under normoglycemic or hyperglycemic conditions and showed the improvement of major biochemical pathways by LAB. Potential involvement of the nuclear factor erythroid 2-related factor-2 (Nrf2)--antioxidant responsive element (ARE)-NAD(P)H: quinone oxidoreductase-1 (NQO1) pathway was assessed using siRNA methods. We found that LAB activates the NQO1 via the Nrf2-ARE pathway, which plays an important role in inhibition of the major molecular mechanisms that lead to vascular damage and the proliferation and migration of VSMCs. Together, these findings demonstrate that the induction of the Nrf2-ARE-NQO1 pathway by LAB could be a new therapeutic strategy to prevent diabetic atherosclerosis.

Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats.

Ginseng has been reported to ameliorate hyperglycemia in experimental and clinical studies; however, its mechanism of action remains unclear. In this study, we investigated the metabolic effects and putative molecular mechanisms of Korean red ginseng (KRG, Panax ginseng) in animal models for type 2 diabetes mellitus (T2DM) and peripheral insulin-responsive cell lines. Korean red ginseng was administered orally at a dose of 200 mg/(kg d) to Otsuka Long-Evans Tokushima fatty rats for 40 weeks. Initially, chronic administration of KRG reduced weight gain and visceral fat mass in the early period without altering food intake. The KRG-treated Otsuka Long-Evans Tokushima fatty rats showed improved insulin sensitivity and significantly preserved glucose tolerance compared with untreated control animals up to 50 weeks of age, implying that KRG attenuated the development of overt diabetes. KRG promoted fatty acid oxidation by the activation of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation of acetyl-coenzyme A carboxylase in skeletal muscle and cultured C2C12 muscle cells. Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 by KRG treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle. Although these findings suggest that KRG is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK, further clinical studies are required to evaluate the use of KRG as a supplementary agent for T2DM.

Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model.

BACKGROUND: Asthma is a major health problem worldwide, and the morbidity and mortality caused by asthma are on the rise. Corticosteroid therapies for asthma treatment frequently induce many side effects. Therefore, the development of new medicines that have both high efficacy and fewer side effects has been a scientific challenge. Here we tested the effect of ginsan, a polysaccharide derived from Panax ginseng, against allergic reaction in an ovalbumin (OVA)-induced murine asthmatic model in comparison with dexamethasone, and investigated its underlying mechanism. METHODS: To induce murine asthma, mice were sensitized and challenged with OVA. Ginsan or dexamethasone was administered by injection 3 times a week. Airway hyperresponsiveness, airway inflammation and lung pathology were assessed in order to evaluate the effect of ginsan against asthma. RESULTS: Ginsan treatment reduced airway hyperresponsiveness, remodeling and eosinophilia. These effects of ginsan were equivalent to those of dexamethasone. Ginsan treatment decreased the IL-5 level in the supernatant of cultured splenocytes, while IFN-gamma and serum IgE were not altered. To elucidate the mechanism of ginsan, expression of inflammation-related genes were screened. Interestingly, ginsan treatment upregulated cyclooxygenase (COX)-1 and COX-2 mRNA, and expression of their proteins in the lung were also increased. PGE(2) in the bronchoalveolar lavage fluid was also increased by the ginsan treatment. Lastly, ginsan inhibited the allergic reaction aggravated by COX inhibitor (indomethacin). CONCLUSION: Ginsan has anti-asthmatic effects, which seem to be partially mediated by enhancing the synthesis of COX gene products.

Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury.

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate B, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty.

Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics.

BACKGROUND/AIMS: The androgen dehydroepiandrosterone (DHEA) attenuates allergic inflammatory airway reactions by down-regulating the Th2 response in mice. The purpose of this study was to investigate whether DHEA suppresses Th2 cytokine production in cultured peripheral blood mononuclear cells (PBMCs) from asthmatic patients. METHODS: Sixty-one consecutive suspected asthmatic or non-asthmatic men underwent tests for asthma. PBMCs from each subject were cultured with and without DHEA (0.01~10 microM) for 48 h. The concentrations of interferon (IFN)-gamma, interleukin (IL)-5, and IL-10 in the culture supernatant were measured via an enzyme-linked immunosorbent assay. RESULTS: In PBMCs from subjects exhibiting methacholine airway hyperresponsiveness (AHR), DHEA significantly suppressed IL-10, IL-5, and IFN-gamma production in a dose-dependent manner (all p<0.001) and tended to increase the IFN-gamma/IL-5 ratio (p=0.087). DHEA (10 microM) suppressed cytokine production to a greater degree in subjects with AHR compared with those without AHR (IL-5: 24.0+/-7.8% vs. 40.9+/-3.6%, p<0.01; IFN-gamma: 29.7+/-7.0% vs. 54.5+/-5.1%, p<0.01). Cytokine suppression was significantly related to AHR, serum total IgE levels, and skin reactivity to house dust mites. CONCLUSIONS: DHEA suppressed both Th1 and Th2 responses, with a Th1 bias, and the degree of suppression was associated with the severity of AHR or atopy. Therefore, DHEA may be a useful therapy for asthma.

Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732.

The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs 170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.

Antidiabetic agents from medicinal plants.

Currently available therapeutic options for non-insulin-dependent diabetes mellitus, such as dietary modification, oral hypoglycemics, and insulin, have limitations of their own. Many natural products and herbal medicines have been recommended for the treatment of diabetes. The present paper reviews medicinal plants that have shown experimental or clinical antidiabetic activity and that have been used in traditional systems of medicine; the review also covers natural products (active natural components and crude extracts) isolated from the medicinal plants and reported during 2001 to 2005. Many kinds of natural products, such as terpenoids, alkaloids, flavonoids, phenolics, and some others, have shown antidiabetic potential. Particularly, schulzeines A, B, and C, radicamines A and B, 2,5-imino-1,2,5-trideoxy-L-glucitol, beta-homofuconojirimycin, myrciacitrin IV, dehydrotrametenolic acid, corosolic acid (Glucosol), 4-(alpha-rhamnopyranosyl)ellagic acid, and 1,2,3,4,6-pentagalloylglucose have shown significant antidiabetic activities. Among active medicinal herbs, Momordica charantia L. (Cucurbitaceae), Pterocarpus marsupium Roxb. (Leguminoceae), and Trigonella foenum graecum L. (Leguminosae) have been reported as beneficial for treatment of type 2 diabetes.

Delayed treatment with lithospermate B attenuates experimental diabetic renal injury.

Extracellular matrix (ECM) accumulation in the glomerular mesangium is a characteristic feature of diabetic nephropathy. While transforming growth factor-beta1 (TGF-beta1) is the final mediator of ECM accumulation, reactive oxygen species (ROS) and protein kinase C (PKC) are the upstream signaling molecules that mediate hyperglycemia-induced ECM expansion. Magnesium lithospermate B (LAB) is an active component isolated from Salvia miltiorrhizae with known renoprotective properties due to its antioxidative effects. Thus, the present study examined the effects of LAB on renal injury in streptozotocin-induced diabetic rats (STZR) and on the activation of mesangial cells cultured under high glucose conditions. Ten micrtograms of LAB/kg per day was started 8 wk after streptozotocin injection and continued for a period of 8 wk. It significantly suppressed renal malondialdehyde (MDA), microalbuminuria, glomerular hypertrophy, mesangial expansion, and the upregulation of renal TGF-beta1, fibronectin, and collagen in STZR without significantly affecting plasma glucose. Both 30 mM of glucose and 100 uM of H(2)O(2) significantly increased TGF-beta1 and fibronectin protein secretion by mesangial cells. LAB at 10 micro g/ml inhibited high glucose- and H(2)O(2)-induced TGF-beta1 and fibronectin secretion. LAB also inhibited glucose-induced intracellular ROS generation and PKC activation in mesangial cells, but it did not directly inhibit PKC activity at dosages that inhibited ROS generation. The in vitro data of this study show that LAB inhibits ROS generation leading to PKC activation and TGF-beta1 and fibronectin upregulation in mesangial cells cultured under high glucose conditions. Moreover, delayed treatment with LAB was found to significantly suppress the progression of renal injury in STZR. LAB may become a new therapeutic agent for the treatment of diabetic nephropathy.

Effective isolation of magnesium lithospermate B and its inhibition of aldose reductase and fibronectin on mesangial cell line.

We developed an effective isolation method of magnesium lithospermate B from Salviae miltiorrhizae Radix and found for the first time that magnesium lithospermate B shows strong in vitro inhibition (IC50=0.04 microM) of aldose reductase (AR), 2.5 times than that of clinically used epalrestat (IC50=0.1 microM) and accumulation of fibronectin dose dependently.