Showing papers by "Youn-Chul Kim published in 2017"
TL;DR: Steppogenin exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines.
Abstract: Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions are related to the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-κB and MAPK is vital to prevent microglial activation and confer resistance against neuronal injury. In this study, steppogenin (1) isolated from Cudrania tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover, western blot analysis and immunofluorescence revealed that the nuclear translocation of NF-κB was inhibited in LPS-induced BV2 and rat primary microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2-terminal kinase (JNK) and p38 MAPK signaling. These results suggested that steppogenin (1) exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines.
41 citations
TL;DR: The inhibitory function of 4 was confirmed based on decreases in inducible nitric oxide synthesis and cyclooxygenase-2 gene expression, and 4 was found to suppress the phosphorylation of inhibitor kappa B-α, interrupt the nuclear translocation of nuclear factor kappa A, and decrease the activation of p38 mitogen-activated protein kinase.
Abstract: After the chemical investigation of the ethyl acetate extract of the marine-derived fungal strain Penicillium sp. SF-5629, the isolation and structural elucidation of eight secondary metabolites, including (3R,4S)-6,8-dihydroxy-3,4,7-trimethylisocoumarin (1), (3S,4S)-sclerotinin A (2), penicitrinone A (3), citrinin H1 (4), emodin (5), ω-hydroxyemodin (6), 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (7), and 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (8) were carried out. Evaluation of the anti-inflammatory activity of these metabolites showed that 4 inhibited nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated BV2 microglia, with IC50 values of 8.1 ± 1.9 and 8.0 ± 2.8 μM, respectively. The inhibitory function of 4 was confirmed based on decreases in inducible nitric oxide synthesis and cyclooxygenase-2 gene expression. In addition, 4 was found to suppress the phosphorylation of inhibitor kappa B-α, interrupt the nuclear translocation of nuclear factor kappa B, and decrease the activation of p38 mitogen-activated protein kinase.
32 citations
TL;DR: Three new benzaldehydes (1–3) and two new dioxopiperazine alkaloids (4 and 5) were isolated from Antarctic marine-derived Aspergillus sp.
27 citations
TL;DR: It was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity.
Abstract: Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (2-9). The structures of these metabolites (1-9) were established by comprehensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). In vitro anti-inflammatory effects of these metabolites were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Among these metabolites, 3-9 were shown to strongly inhibit LPS-induced overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) with IC50 values ranging from 1.9 μM to 18.1 μM, and from 2.8 μM to 18.7 μM, respectively. In the further evaluation of signal pathways involved in these effects, the most active compound, (10E,15S)-10,11-dehydrocurvularin (8) attenuated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages. Furthermore, compound 8 was shown to suppress the upregulation of pro-inflammatory mediators and cytokines via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway, but not through the mitogen-activated protein kinase (MAPK) pathway. Based on the comparisons of the different magnitude of the anti-inflammatory effects of these structurally-related metabolites, it was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity.
26 citations
TL;DR: The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system.
Abstract: Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl₄-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system.
22 citations
TL;DR: It is suggested that Puerariae radix extract is an effective inhibitor of RANKL-induced osteoclastogenesis and may be a potent therapeutic agent for bone-related diseases such as osteoporosis, rheumatoid arthritis, and periodontitis.
Abstract: Puerariae radix, the dried root of Pueraria lobate Ohwi, is known to prevent bone loss in ovariectomized mice; however, the precise molecular mechanisms are not understood. In this study, we investigated the effects and underlying mechanisms of action of Puerariae radix extract (PRE) on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. PRE dose-dependently inhibited osteoclast differentiation and formation, decreased the bone-resorbing activity of osteoclasts, and downregulated the expression of osteoclast differentiation marker genes. The expression of osteoclastogenic factors produced by PRE-treated osteoblasts such as RANKL, macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) was comparable to that of untreated (control) cells. However, the formation of osteoclasts via bone marrow cell and calvaria-derived osteoblast co-cultures was suppressed by PRE treatment. Therefore, the inhibitory effects of PRE on osteoclastogenesis clearly targeted osteoclasts, but not o...
22 citations
TL;DR: Ostruthin and ninhvanin were shown to suppress LPS-induced iNOS and COX-2 protein expression and might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.
Abstract: Context: Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.Objective: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds.Materials and methods: Cytotoxicity of isolated compounds (5–40 μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 μM) on nitrite and PGE2 concentrations were determined using Griess reaction and PGE2 ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS).Results: Seven coumarins were isolated and id...
18 citations
TL;DR: Chemical investigation of an acidic methanol extract of the whole plants of D. metel resulted in the isolation of five new steroidal saponins, named metelosides A‐E, and four known compounds, which were identified by spectroscopic methods.
15 citations
TL;DR: It is suggested that alcoholic aqueous leaf extract of Vitis labruscana promotes phosphorylation of Akt, ERK, and CREB in the hippocampus and ameliorates scopolamine-induced memory impairment in mice.
14 citations
TL;DR: The results suggest that APV has a significant protective effect against diabetic renal dysfunction including inflammation and fibrosis through disruption of the TGF-[Formula: see text]/Smad signaling.
Abstract: Diabetic nephropathy is both the most common complication and the leading cause of mortality associated with diabetes. Prunella vulgaris, a well-known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. This study confirmed whether an aqueous extract of Prunella vulgaris (APV) suppresses renal inflammation and fibrosis. In human mesangial cell (HMC), pretreatment of APV attenuated 25[Formula: see text]mM HG-induced suppressed TGF-[Formula: see text] and Smad-2/4 expression; it increased the expression level of Smad-7. Connective tissue growth factor (CTGF) and collagen IV, fibrosis biomarkers, were significantly decreased by APV. APV suppressed inflammatory factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). APV inhibited activation and translocation of nuclear factor kappa-B (NF-[Formula: see text]B) in HG-stimulated HMCs. Moreover, APV significantly improved HG-induced ROS in a dose-dependent manner. In diabetic rat models, APV significantly decreased blood glucose, blood urea nitrogen (BUN) and ameliorated plasma creatinine (PCr). APV reduced the PAS positivity staining intensity and basement membrane thickening in glomeruli of diabetic rats. Fibrosis related proteins such as collagen IV and TGF-[Formula: see text]1 were also inhibited by APV. These results suggest that APV has a significant protective effect against diabetic renal dysfunction including inflammation and fibrosis through disruption of the TGF-[Formula: see text]/Smad signaling. Therefore, APV may be useful in potential therapies that target glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.
13 citations
TL;DR: Data reveal that cearoin induces autophagy, ERK activation and apoptosis in neuroblastoma SH-SY5Y cells, which is mediated primarily by ROS generation, suggesting its therapeutic application for the treatment of neuroblastomas.
Abstract: Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA fluorescence assay and Griess assay were used for the measurement of intracellular reactive oxygen species (ROS) and nitric oxide (NO), respectively. Western blot analysis was performed to clarify the molecular pathway involved. Cearoin induced cell death in a dose-dependent manner. Cearoin increased the phosporylation of ERK, the conversion of LC3B-I to LC3B-II, decrease in Bcl2 expression, the activation of caspase-3, and the cleavage of PARP, indicating the induction of autophagy and apoptosis. Furthermore, cearoin treatment increased the production of ROS and NO. Co-treatment with the antioxidant N-acetylcysteine completely abolished cearoin-mediated autophagy, ERK activation and apoptosis, suggesting the critical role of ROS in cearoin-induced anticancer effects. Moreover, co-treatment with ERK inhibitor PD98059 partially reversed cearoin-induced cell death, indicating the involvement of ERK in cearoin anticancer effects. These data reveal that cearoin induces autophagy, ERK activation and apoptosis in neuroblastoma SH-SY5Y cells, which is mediated primarily by ROS generation, suggesting its therapeutic application for the treatment of neuroblastomas.
TL;DR: The present study suggested that the neuroprotective effect of T. coreanum is associated with induction of HO-1 expression and Nrf2 translocation to the nucleus, and exhibits a promising function in prevention of neurodegeneration.
Abstract: Taraxacum coreanum Nakai is a dandelion that is native to Korea, and is widely used as an edible and medicinal herb. The present study revealed the neuroprotective effect of this plant against glutamate-induced oxidative stress in HT22 murine hippocampal neuronal cells. Ethanolic extracts from the aerial (TCAE) and the root parts (TCRE) of T. coreanum were prepared. Both extracts were demonstrated, by high performance liquid chromatography, to contain caffeic acid and ferulic acid as representative constituents. TCAE and TCRE significantly increased cell viability against glutamate-induced oxidative stress in mouse hippocampal HT22 cells. Western blot analysis revealed that treatment of HT22 cells with the extracts induced increased expression of the enzyme heme oxygenase-1 (HO-1), compared with untreated cells, in a concentration-dependent manner. Increased HO-1 enzymatic activity, compared with untreated cells, was also demonstrated following treatment with TCAE and TCRE. In addition, western blot analysis of the nuclear fractions of both TCAE and TCRE-treated HT22 cells revealed increased levels of nuclear factor erythroid 2 like 2 (Nrf2) compared with untreated cells, and decreased Nrf2 levels in the cytoplasmic fraction compared with untreated cells. The present study suggested that the neuroprotective effect of T. coreanum is associated with induction of HO-1 expression and Nrf2 translocation to the nucleus. Therefore, T. coreanum exhibits a promising function in prevention of neurodegeneration. Further studies will be required for the isolation and the full characterization of its active substances.
TL;DR: Inhibitory effects of NO production in RAW 264.7 macrophages guided the isolation of nine prenylated isoflavones, including a new cudraisoflavone L and eight known metabolites from the leaves of Cudrania tricuspidata, showing promising cytotoxic effects toward HL-60 cells.
TL;DR: PVN was found to inhibit cell proliferation in a concentration- and time-dependent manner in the human osteosarcoma cell lines studied and induce apoptosis, as evidenced by Annexin V+ and TUNEL+ cells.
Abstract: This study was performed to examine the anticancer and anti-metastatic effects of 4-parvifuran (PVN), a novel flavonoid isolated from the heartwood of Dalbergia odorifera, and to study its underlying signaling pathway in human osteosarcoma cells. In the present study, PVN was found to inhibit cell proliferation in a concentration- and time-dependent manner in the human osteosarcoma cell lines studied (MG-63 and U-2 OS) and induce apoptosis, as evidenced by Annexin V+ and TUNEL+ cells. Cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 were up-regulated while anti-apoptotic proteins including Bcl-2, Bcl-xL, and survivin were down-regulated after treatment with PVN. Matrigel cell migration assay, invasion assay, and soft agar assay were used to show that PVN effectively suppressed cell migration and invasion and colony formation in osteosarcoma cells. Protein and mRNA levels of MMP-2 and MMP-9 were reduced by PVN in a concentration-dependent manner. Furthermore, PVN inhibited Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), mitogen-activated protein kinases (MAPKs) including JNK, ERK, p38 kinase, and cAMP response element-binding protein (CREB). Therefore, this is the first study to demonstrate that PVN might be a novel anticancer and anti-metastatic agent for the treatment of osteosarcoma through the inhibition of JAK2/STAT3, MAPKs, and CREB signaling pathways.
TL;DR: In this article, the guainane sesquiterpenes 1β,5α,7β-guaiane-4β,10α,11-triol (1) and 1α,5β,7α-11-guaiene-2α,3β,4α, 4α, 10α,13-pentaol (2), along with eight known compounds: pterodontriol B (3), disciferitriol (4), scopolamine (5), kaempferol 3-O
TL;DR: Results suggested that T. crispa or P. weberi may offer potential for therapeutic applications in liver disease characterized by oxidative stress, and exhibited hepatoprotective effects on t‑BHP‑induced cytotoxicity in HepG2 cells.
Abstract: Liver diseases are considered to be primary contributors to morbidity and mortality rates in humans. Oxidative stress is critical in liver injury, and oxidant‑induced liver injury may be caused by toxins, including tert‑butyl hydroperoxide (t‑BHP). The present study investigated the hepatoprotective activities of 64 crude ethanol extracts of Cambodian medicinal plants against t‑BHP‑induced cytotoxicity in human liver‑derived HepG2 cells, and assessed their cytoprotective mechanism pertaining to the expression of heme oxygenase (HO)‑1 and nuclear factor E2‑related factor 2 (Nrf2). Protective effects in HepG2 cells were determined by MTT assay. Protein expression levels of HO‑1 and Nrf2 were determined by western blotting and mRNA expression levels were determined by reverse transcription‑quantitative polymerase chain reaction. Of the 64 extracts, 19 extracts exhibited high hepatoprotective activities: Ampelocissus martini, Bauhinia bracteata, Bombax ceiba, Borassus flabellifer, Cardiospermum halicacabum, Cayratia trifolia, Cinnamomum caryophyllus, Cyperus rotundus, Dasymaschalon lomentaceum, Ficus benjamina, Mangifera duperreana, Morinda citrifolia, Pandanus humilis, Peliosanthes weberi, Phyllanthus emblica, Quisqualis indica, Smilax glabra, Tinospora crispa and Willughbeia cochinchinensis, with half maximal effective concentrations ranging between 59.23 and 157.80 µg/ml. Further investigations revealed that, of these 19 extracts, HO‑1 and Nrf2 were expressed in P. weberi and T. crispa expressed in a dose‑dependent manner. In addition, the activities of reactive oxygen species were suppressed following treatment of these two extracts in t‑BHP‑induced HepG2 cells. These results indicated that, of the 64 Cambodian plants, P. weberi and T. crispa exhibited hepatoprotective effects on t‑BHP‑induced cytotoxicity in HepG2 cells, possibly by the induction of Nrf2‑mediated expression of HO‑1. Taken together, these results suggested that T. crispa or P. weberi may offer potential for therapeutic applications in liver disease characterized by oxidative stress.
TL;DR: The results showed that SB has differential actions according to its treatment dose and the type of cells and tissues, and further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.
Abstract: Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1β, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1β. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.
TL;DR: A new iridoid glycoside, buddlemacroside A (1) and 15 known compounds, including 6-α-L-(4″-O-trans-p-coumaroyl) rhamnopyranosylcatalpol (2), 6-β-L(2″-caffeoyl), 6β-R(2)-R(3), salidrosi...
Abstract: A new iridoid glycoside, buddlemacroside A (1) and 15 known compounds, including 6-α-L-(4″-O-trans-p-coumaroyl)rhamnopyranosylcatalpol (2), 6-α-L-(2″-caffeoyl)rhamnopyranosylcatalpol (3), salidrosi...
TL;DR: The root bark of Morus alba L was extracted with 80% aqueous MeOH and the concentrated extract was partitioned with EtOAc, n-BuOH, and H2O fractions as mentioned in this paper.
Abstract: The root bark of Morus alba L. were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH, and H2O fractions. The repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatographies of the EtOAc fraction led to isolation of 12 phenolic compounds. The chemical structures of the compounds were determined as sanggenol Q (1), sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), sanggenon N (8), sanggenon G (9), mulberrofuran G (10), mulberrofuran C (11), and moracin E (12). All isolated compounds were evaluated for inhibit lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages.