Se Chan Kang

Coordination-Driven Self-Assembly and Anticancer Potency Studies of Ruthenium-Cobalt-Based Heterometallic Rectangles.

Three new cobalt-ruthenium heterometallic molecular rectangles, 1-3, were synthesized through the coordination-driven self-assembly of a new cobalt sandwich donor, (η5 -Cp)Co[C4 -trans-Ph2 (4-Py)2 ] (L; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [(p-cymene)2 Ru2 (OO∩OO)2 Cl2 ] [OO∩OO: oxalato (A1 ), 5,8-dioxido-1,4-naphthoquinone (A2 ), or 6,11-dioxido-5,12-naphthacenedione (A3 )]. All of the self-assembled architectures were isolated in very good yield (92-94 %) and were fully characterized by spectroscopic analysis; the molecular structures of 2 and 3 were determined by single-crystal X-ray diffraction analysis. The anticancer activities of bimetallic rectangles 1-3 were evaluated with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, an autophagy assay, and Western blotting. Rectangles 1-3 showed higher cytotoxicity than doxorubicin in AGS human gastric carcinoma cells. In addition, the autophagic activities and apoptotic cell death ratios were increased in AGS cells by treatment with 1-3; the rectangles induced autophagosome formation by promoting LC3-I to LC3-II conversion and apoptotic cell death by increasing caspase-3/7 activity. Our results suggest that rectangles 1-3 induce gastric cancer cell death by modulating autophagy and apoptosis and that they have potential use as agents for the treatment of human gastric cancer.

Cynanchum wilfordii Radix attenuates liver fat accumulation and damage by suppressing hepatic cyclooxygenase-2 and mitogen-activated protein kinase in mice fed with a high-fat and high-fructose diet

Excessive consumption of fat and fructose augments the pathological progression of nonalcoholic fatty liver disease through hepatic fibrosis, inflammation, and hepatic de novo lipogenesis. We hypothesized that supplementation with Cynanchum wilfordii extract (CWE) decreases fat accumulation in the liver by suppressing cyclooxygenase-2 (COX-2), the nuclear translocation of nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinase (MAPK). The beneficial effect of CWE was evaluated in a murine model of nonalcoholic fatty liver disease. Mice were fed either a normal diet or an atherogenic diet with fructose (ATHFR) in the presence or absence of CWE (50, 100, or 200 mg/kg; n=6/group). Treatment with ATHFR induced a hepatosplenomegaly-like condition (increased liver and spleen weight); this pathological change was attenuated in the presence of CWE. The ATHFR group exhibited impaired liver function, as evidenced by increased blood levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, fat accumulation in the liver, and lipid profiles. Supplementation of CWE (100 and 200 mg/kg, P<.05) ameliorated these impaired liver functions. Atherogenic diet with fructose increased the protein levels of COX-2 and p38 MAPK, as well as the nuclear translocation of NF-κB. These signaling pathways, which are associated with the inflammatory response, were markedly suppressed after CWE treatment (100 and 200 mg/kg). In summary, CWE supplementation reduced high-fat and high-fructose diet-induced fat accumulation and damage in the liver by suppressing COX-2, NF-κB, and p38 MAPK.

Anti-obesity effect of Crinum asiaticum var. japonicum Baker extract in high-fat diet-induced and monogenic obese mice

This study determined the anti-obesity effect of Crinum asiaticum var. japonicum Baker extract (CAE) on adipocytes and obese mice. The inhibitory effects of CAE on adipocyte differentiation and adipogenesis were determined using differentiation induction medium in 3T3-L1 cells. To get an insight into underlying molecular actions of CAE, we investigated the changes in the expression levels of genes involved in lipogenesis by CAE treatment using qRT-PCR. CAE strongly suppressed adipocyte differentiation through downregulation of PPARγ, C/EBPα, C/EBP β, and aP2. CAE treatment could also suppress the expression levels of ACC, FAS, LPL and HMGCR gene in 3T3-L1 cells. Male C57BL/6 strain and C57BL/6J-ob/ob strain mice were fed with HFD containing 60% fat and normal diet in the presence or absence of 25, 50, and 100mg/kg CAE for 7 weeks. CAE supplementation could highly suppress the body weight gain and epididymal fat accumulation without changes in food uptake in both obese models. Increases in total cholesterol, LDL-cholesterol and triglyceride were highly suppressed in the presence of CAE. In summary, CAE has an anti-obesity effect and this anti-obesity potential might be associated with downregulation of genes involved in adipocyte differentiation and lipogenesis.

Quinic acid inhibits vascular inflammation in TNF-α-stimulated vascular smooth muscle cells

Atherosclerosis is a chronic inflammatory disease, and the increased expression of adhesion molecules on vascular smooth muscle cells contributes to the progression of vascular disease. Quinic acid (QA) has been shown to possess radioprotection, anti-neuroinflammatory, and anti-oxidant activities; however, an anti-vascular inflammatory effect has not been reported. This study investigated the effect of QA on the expression of vascular cell adhesion molecule-1 (VCAM-1) stimulated by TNF-α in MOVAS cells. Pre-incubation of MOVAS cells, the mouse vascular smooth muscle cell line for 2h with QA (0.1, 1 and 10 μg/mL) dose-dependently inhibits TNF-α-induced mRNA and protein expression of VCAM-1 and monocyte adhesion. QA inhibits TNF-α-stimulated phosphorylation of MAP kinase and NK-κB activation. Our results indicate that QA inhibits the TNF-α-stimulated induction of VCAM-1 in VSMC by inhibiting the MAP kinase and NF-κB signaling pathways and the adhesion capacity of VSMC, which may explain the ability of QA to inhibit vascular inflammation such as atherosclerosis.

Gamma irradiation-induced liver injury and its amelioration by red ginseng extract

Radiation therapy is associated with liver damage and late liver injury. The hepatoprotective effect of Korean Red Ginseng (KRG) was determined in whole-body gamma-irradiated (γIR) mice. KRG at a dose of 10 and 50 mg/kg body weight was administrated to male C57BL/6 mice (each group, n=5) intraperitoneally for five days before whole-body γIR (6.5 Gy). Three days after γIR, serum and liver tissue were collected and analysed. Pretreatment with KRG suppressed serum alkaline phosphatase (ALP), alkaline aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl-transferase (GGT) activities. It also caused a marked increase in cyclooxygenase-2 (COX-2) and tumour growth factor-β1 (TGF-β1) expression associated nuclear factor-κB (NF-κB) activation in the liver. Extracellular signal-regulated kinases (ERKs) were also activated by irradiation. KRG treatment before irradiation could strongly suppress COX-2, TGF-β1, and ERK activation in the liver. Pretreatment with KRG may alleviate the severity of radiation-induced liver injury and fibrosis.

Prunus mume leaf extract lowers blood glucose level in diabetic mice.

Abstract Context Diabetes is a common metabolic disease with long-term complications. Prunus mume Sieb. et Zucc. (Rosaceae) fruits have shown to ameliorate glucose intolerance. However, the antidiabetic effects of P. mume leaves have not been investigated. Objective This study evaluated the effects of P. mume leaf 70% ethanol extract (PMLE) on alleviating diabetes in vivo and in vitro. Materials and methods PMLE was fractionated into n-hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water. Polyphenol and flavonoid contents in PMLE fractions were determined using Folin–Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. We evaluated α-glucosidase inhibition using a microplate reader at 400 nm. Adipocyte differentiation by lipid accumulation was measured using Nile Red staining. Male imprinting control region (ICR) mice were injected with streptozotocin (STZ, 100 mg/kg, i.p.). High-fat diets were provided for three weeks prior to PMLE treatments to induce type 2 diabetes. PMLE (0, 5, 25 or 50 mg/kg) was administrated for four weeks with high-fat diets. Results The EtOAc fraction of PMLE inhibited α-glucosidase activity (IC50 = 68.2 μg/mL) and contained 883.5 ± 14.9 mg/g of polyphenols and 820.1 ± 7.7 mg/g of flavonoids. The 50 mg/kg PMLE supplement reduced 40% of blood glucose level compared to obese/diabetes mice. Obese/diabetic mice treated with 50 mg/kg PMLE showed a lower level of triacylglycerol (320.7 ± 20.73 mg/dL) compared to obese/diabetes mice (494.9 ± 14.80 mg/dL). Conclusion The data demonstrate that P. mume leaves exert antidiabetic effects that may be attributable to high concentrations of polyphenols and flavonoids.

The suppressive effect of the three-herb extract mixture on vascular and liver inflammation in atherogenic diet with high fructose-fed mice

Abstract Context: Cynanchum wilfordii (Maximowicz) Hemsley (Apocynaceae), Arctium lappa L. var. rubescens Frivald (Asteraceae) and Dioscorea opposite Thunb (Dioscoreaceae) root extracts have been widely used as an alternative for intervening obesity. Objectives: The synergistic effect of three-herb mixture of C. wilfordii, A. lappa and D. opposita was determined on aortic and liver inflammatory responses. Materials and methods: CWE, ALE and DOE were prepared from the root of C. wilfordii, A. lappa and D. opposite by 70% ethanol extraction, respectively. CADE was prepared using a powder mixture of 2 CWE:1 ALE:1 DOE. C57BL/6 mice were fed an atherogenic diet combined with 10% fructose (ATHFR) in the presence of 200 mg/kg/day CWE, ALE, DOE or CADE for 8 weeks (each group, n = 6). Biochemical profiles, protein expression of vascular cell adhesion molecule-1 (VCAM-1) on the aorta and liver were determined. Results: CADE could significantly suppress the protein expression of VCAM-1 in both the aorta and liver (80% reduction) compared to ATHFR-fed mice. Impairment of liver function was significantly ameliorated by CADE supplement, as determined by GOT (60% reduction) and GPT (51% reduction) levels. Conclusions: CADE should be considered when developing medications to suppress the vascular and liver inflammatory responses for individuals who are either non-responsive or resistant to lipid-lowering drugs.

Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice

Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n = 6; p < 0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n = 6; p < 0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n = 6; p < 0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.

Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice

The extract of the Momordica charantia fruit (MCE) is recognized as an alternative treatment for diabetes. The extract of Ligularia fischeri leaves (LFE) is traditionally used as a folk medicine for treating inflammatory diseases in Korea as well. In this study, we investigated the synergistic effect of MCE combined with LFE on antihyperglycemic and antihyperlipidemic potentials. Based on the α-glucosidase inhibitory effect and promotion of adipocyte differentiation in the 3T3-L1 cell line, the MLM was prepared with MCE:LFE (8:2 weight:weight). MLM showed the synergistic effects in the promotion of the glucose uptake rate, suppression of dipeptidyl peptidase-4 (DPP-4) mRNA expression, upregulation of an insulin receptor substrate and glucose transporter type-4 expression, and an increase in insulin-associated signaling in C2C12 cells. In addition, the efficacy of peroxisome proliferator-activated receptor-γ agonism and glucose uptake rate by MLM supplementation was significantly enhanced in vitro. Then, the antihyperglycemic and antihyperlipidemic effects of MCE, LFE, and MLM at the dose of 50, 100, and 200 mg/kg/day (n = 6 per each group) were determined in streptozotocin (STZ)-insulted mice fed an atherogenic diet (ATH) for 4 weeks. In addition, MLM (50, 100, and 200 mg/kg/day, n = 5 per each group) was supplemented in ATH-fed db/db mice for 10 weeks. Compared with MCE or LFE alone, MLM supplementation led to a more significant reduction of glucose levels in both STZ/ATH and db/db/ATH mice as well as lowered lipid profiles in STZ/ATH mice. In addition, the stimulation of islet of Langerhans regeneration was more pronounced by MLM supplementation in both mice models. In conclusion, antihyperglycemic and antihyperlipidemic effects were strengthened by the combined extracts of L. fischeri and M. charantia (MLM) in diabetes-mimicking mice.

Hyperoside suppresses tumor necrosis factor α-mediated vascular inflammatory responses by downregulating mitogen-activated protein kinases and nuclear factor-κB signaling

Vascular inflammation has been suggested to play a key role in the initiation and progression of atherosclerosis. Hyperoside (HPS) is a plant-derived quercetin 3-d-galactoside reported to have anti-inflammatory, anti-oxidant, anti-cancer, anti-hyperglycemic, anti-coagulant, and cardioprotective activities. However, the effects of HPS on vascular inflammation have not been studied. Therefore, in this study, we investigated the suppressive effect of HPS on tumor necrosis factor-α (TNFα)-dependent inflammatory responses in MOVAS-1 cells, a murine vascular smooth muscle cell (VSMC) line. HPS did not show any significant cytotoxicity up to 10 μg/mL over 24 h. TNFα challenge of VSMCs significantly increased the mRNA (3-fold) and protein expression (20-fold) of vascular cell adhesion molecule-1 (VCAM-1). However, these increases were abolished in the presence of HPS. Additionally, HPS significantly decreased monocyte adhesion to TNFα-stimulated VSMCs in a dose-dependent manner. Further, TNFα challenge induced activation of mitogen-activated protein kinases (MAPKs), such as p38 MAPK (38.0 ± 3.08 fold), JNK (51.6 ± 2.26 fold), and ERK (14.1 ± 0.77 fold); expression of nuclear factor-κB (NF-κB; ≅ 4-fold) and TNF receptor 1 (TNFR1; 2.7 ± 0.198 fold) were also increased. Notably, the TNFα-induced expression of these molecules was also significantly inhibited by the presence of HPS. Given that p38 MAPK, JNK, ERK, NF-κB, and TNFR1 all play regulatory roles in the expression of VCAM-1, this study provides insight into the mechanism of action of HPS. In summary, HPS can inhibit TNFα-mediated vascular inflammatory responses and has potential as a new anti-atherosclerotic drug.