Samkeun Lee

Immune-suppressive activity of punicalagin via inhibition of NFAT activation.

Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.

Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model

We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway.

The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress mouse exercise model

ETHNOPHARMACOLOGICAL RELEVANCE Gongjin-Dan is a representative traditional Oriental medicine herbal drug that has been used to treat chronic fatigue symptoms for several hundred years. We evaluated the anti-fatigue effects of Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse model. METHODS AND MATERIALS Balb/C male mice underwent an extreme treadmill-based running stress (1-h, 5 days/week), and daily oral administration of distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100 mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with behavioral tests (exercise tolerance and swimming tests), and the corresponding mechanisms were investigated based on oxidative stress and inflammatory cytokine and stress hormone levels in skeletal muscle, sera, and brain tissue. RESULTS Gongjin-Dan significantly increased exercise tolerance and latency times but reduced the number of electric shocks and immobilization time on the treadmill running and swimming tests, compared with the control group. Gongjin-Dan also significantly ameliorated alterations in oxidative stress-related biomarkers (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interferon-γ) and glycogen and L-lactate levels in skeletal muscle, compared with those in the control group. Moreover, Gongjin-Dan considerably normalized the forced running stress-induced changes in serum corticosterone and adrenaline levels, as well as brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan were supported by the results of Western blotting (4-hydroxynonenal and heme oxygenase-1) and the gene expression levels (serotonin receptor and serotonin transporter). CONCLUSION These results support the clinical relevance of Gongjin-Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve attenuation of oxidative and inflammatory reactions in muscle and regulation of the stress response through the hypothalmo-pituitary-adrenal axis.

ALTERNATIVE FORMATION AND CRYSTAL STRUCTURE OF TRIS(ACETYLACETONATO)TITANIUM(HI) FROM TITANOCENE AND 2, 4-PENTANEDIONE

Abstract An alternative route to the formation of tris(acetylacetonato)titanium(III) has been found in the course of studying the reactivity of Cp2Ti toward 2, 4-pentanedione. The crystal structure of tris(acetylacetonato)titanium(III) has been determined.

Alternative Synthesis and Crystal Structures of Titanocene(III)-β-Diketonate Complexes

Abstract Reaction of titanocene prepared from Cp2TiCl2 and 2n-BuLi with β-diketones (β-diketone = 1-phenyl-1,3-butanedione, 1,3-diphenyl-1,3-propanedione, 3-methyl-2,4-pentanedione or 3-ethyl-2,4-pentanedione) afforded the titanocene(III) β-diketonate complex. The compounds [Ti(η5-Cp)2(1-phenyl-1,3-butanedionate)] and [Ti(η5‒Cp)2(1,3-diphenyl-1,3-propanedionate)] have been characterized by X-ray crystallography.

Polymerization of ethylene catalyzed by titanocene(iii) -b-diketonate complex and MMAO

Ethylene polymerizations were performed with a catalytic system composed of titanocene(III)-β-diketonate complex such as [Cp2Ti(III)(1-benzoylacetonato)] or [Cp2Ti(III)(dibenzoylmethanato)] and MMAO. These catalysts are active for the polymerization of ethylene to give high-density polyethylene with high molecular weight.

Gongjin-Dan Enhances Hippocampal Memory in a Mouse Model of Scopolamine-Induced Amnesia

We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory impairment caused by scopolamine injection. BALB/c mice were orally treated with GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and passive avoidance tests were performed to evaluate the animal’s learning and memory. Scopolamine increased the task completing time, the number of total errors (reference and working memory error) in the radial arm maze task, and the latency time in the passive avoidance test, which were significantly ameliorated by treatment with GJD. The GJD treatment also attenuated the scopolamine-induced hyperactivation of acetylcholinesterase activity, and suppression of the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and their receptors in the hippocampus. These effects of GJD were supported by both the doublecortin (DCX)-positive staining and Nissl staining, which were used to measure hippocampal neurogenesis and atrophy, respectively. These findings strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying mechanism might involve the modulation of cholinergic activity.

Synthesis and crystal structures of dichlorocyclopentadienyl β-diketonate titanium complexes

Complexes of acetylacetonatodichlorocyclopentadienyltitanium(IV) (1) and dichlorocyclopentadienyl(2,2,6,6-tetramethyl-3,5-heptanedionato)titanium(IV) (2) have been prepared and their crystal structures determined by X-ray diffraction methods. Complex 1 crystallizes in space group P21/m with a = 7.1893(10), b = 11.7680(17), c = 7.6129(11) Å, β = 109.901(12)°; complex 2 crystallizes in space group P21/n with a = 10.065(2), b = 16.322(3), c = 12.219(2) Å, β = 110.99(3)°. The molecular structures of 1 and 2 can be described as square-based pyramidal, with the centroid of the C5H5 ring occupying the apical site and the bidentate β-diketonate and two chloride ligands occupying the basal positions. The average distances between titanium and oxygen atoms are 1.991(2) and 1.967(3) Å in compounds 1 and 2, respectively.

Synthesis and crystal structure of oxo-bridged binuclear titanium complex [{Ti(acac)2Cl}{TiCp2(Cl)}(μ-O)] and its catalytic reactions toward silation of aldehyde

Abstract Reaction of [Cp2TiCl2] with two equivalents of 2,4-pentanedione in the presence of one equivalent of NEt3 in CH3CN at room temperature yielded oxo-bridged binuclear titanium complex [{Ti(acac)2Cl}{TiCp2(Cl)}(μ-O)], which was characterized crystallographically and spectroscopically. Reaction mixture of oxo-bridged binuclear titanium complex and 2nBuLi catalytically activate the mixture of phenylsilane and aldehyde to yield O-silation products at room temperature.

Biodegradation of 2,4,6-Trinitrotoluene by White-Rot Fungus Irpex lacteus

Abstract White-rot fungus Irpex lacteus degraded TNT significantly in proportion to the culture time. After 48 h incubation, about 95% of TNT was degraded. Two reduced metabolites were identified as 4-amino-2,6-dinitrotoluene (4-ADNT) and 2-amino-4,6-dinitrotoluene (2-ADNT) which was further degraded.