Jae Soon Eun

Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: possible involvement of GABAergic transmission.

This experiment was performed to investigate the anxiolytic-like effects of sanjoinine A, one of the major alkaloid compounds in Zizyphi Spinosi Semen (ZSS), by using experimental paradigms of anxiety in comparison with a known anxiolytic, diazepam. Sanjoinine A (2.0 mg/kg) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of time spent in the center zone and the center zone locomotor distance in the open field box experiment. However, sanjoinine A (0.5, 1.0, 2.0 mg/kg) had no effect on locomotor activity, while diazepam (2.0 mg/kg) significantly reduced locomotor activity. Sanjoinine A (0.5, 1.0, 2.0 mg/kg) did not influence the grip force in the grip strength meter test either. Molecular experiments showed that sanjoinine A (2.0, 5.0 microM) increased chloride influx in cultured cerebellar granule cells. In addition, sanjoinine A (5.0 microM) treatment resulted in over-expression of alpha- and gamma-subunits of GABA(A) receptors and glutamic acid decarboxylase (GAD65/67) in cultured cerebellar granule cells. It is concluded that sanjoinine A may have anxiolytic-like effects in the elevated plus-maze, hole-board test and open field test, and these effects may be mediated by GABAergic transmission.

Acetylcholinesterase inhibitors from the aerial parts ofCorydalis speciosa

In a bioassay-guided search for acetylcholinesterase inhibitors from Korean natural resources, four isoquinoline alkaloids, corynoxidine (1), protopine (2), palmatine (3), and berberine (4) have been isolated from the methanolic extract of the aerial parts ofCorydalis speciosa. Structures of these compounds were elucidated on the basis of spectroscopic techniques. These compounds inhibited acetylcholinesterase activity in a dose-dependent manner, and the IC50 values of compounds1-4 were 89.0, 16.1, 5.8, and 3.3 μM, respectively.

Anti-inflammatory and antinociceptive properties of the leaves of Eriobotrya japonica.

AIM OF THE STUDY The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including coughs and asthma. The present study was designed to validate the anti-inflammatory and antinociceptive properties of the n-BuOH fraction of E. japonica (LEJ) leaves. MATERIALS AND METHODS The anti-inflammatory properties of LEJ were studied using IFN-γ/LPS activated murine peritoneal macrophage model. The antinociceptive effects of LEJ were assessed using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test, and chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. To examine the possible connection of the opioid receptor to the antinociceptive activity of LEJ, we performed a combination test with naloxone, a nonselective opioid receptor antagonist. RESULTS In the IFN-γ and LPS-activated murine peritoneal macrophage model, LEJ suppressed NO production and iNOS expression via down-regulation of NF-κB activation. It also attenuated the expression of COX-2 and the secretion of pro-inflammatory cytokines like TNF-α and IL-6. Moreover, LEJ also demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. In a combination test using naloxone, diminished analgesic activities of LEJ were observed, indicating that the antinociceptive activity of LEJ is connected with the opioid receptor. CONCLUSIONS The results indicate that LEJ had potent inhibitory effects on the inflammatory mediators including nitric oxide, iNOS, COX-2, TNF-α and IL-6 via the attenuation of NF-κB translocation to the nucleus. LEJ also showed excellent antinociceptive activity in both central and peripheral mechanism as a weak opioid agonist. Based on these results, LEJ may possibly be used as an anti-inflammatory and an analgesic agent for the treatment of pains and inflammatory diseases.

Acetylcholinesterase inhibitors from the roots ofangelica dahurica

In the course of finding Korean natural products for acetylcholinesterase (AChE) inhibitory activity, we found that a methanolic extract of the roots ofAngelica dahurica showed significant inhibitory effects on AChE. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of three furanocoumarins, isoimperatorin (1), imperatorin (2) and oxypeucedanin (3), as active principles. These compounds inhibited AChE activity in a dose-dependent manner, and the IC50 values of compounds1–3 were 74.6, 63.7 and 89.1 uM, respectively.

Antitumor and antiinflammatory constituents from celtis sinensis

Eight compounds were isolated from the methanolic extract of the twigs ofCeltis sinensis through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as two triterpenoids, germanicol and epifriedelanol, two amide compounds, frans-N-caffeoyltyramine andcis-N-coumaroyltyramine, two lignan glycoside, pinoresinol glycoside and pinoresinol rutinoside, and two steroids by spectroscopic analysis.

Free radical scavengers from the heartwood ofJuniperus chinensis

The antioxidant activity ofJuniperus chinensis (Cupressaceae) was determined by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl). The methanolic extract ofJ. chinensis heartwood showed the strong antioxidant activity. The antioxidant activity ofn-BuOH soluble fraction was stronger than that of the others, and the fraction was subjected to purification by repeated silica gel and Sephadex LH-20 column chromatography. Quercetin, naringenin, taxifolin, aromadendrin and isoquercitrin were isolated from then-BuOH fraction. Their structures were elucidated by physico-chemical and spectroscopic studies.

Pharmacokinetics and biodistribution of paclitaxel loaded in pegylated solid lipid nanoparticles after intravenous administration

In an effort to develop an alternative formulation of paclitaxel (PTX) suitable for intravenous administration, PTX-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared and their pharmacokinetics and biodistribution were investigated. The pegylated SLNs were comprised of trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers. The prepared pegylated TM-SLNs containing PTX exhibited monodispersed size distribution with 217.4 ± 32.8 nm of mean diameter and 99% of distribution was smaller than 556.2 ± 89.9 nm. After PTX in the pegylated TM-SLNs or commercial product, Taxol®, was intravenously administered into femoral vein of rats, concentrations of PTX in plasma and organs such as liver, spleen, kidney, heart and lung were analyzed by HPLC following liquid extraction. Plasma profile of PTX for pegylated TM-SLNs was similar to that for Taxol®, with no statistically significant difference at each time point, although mean plasma levels of PTX at each point tended to be slightly lower in pegylated TM-SLNs than in Taxol®. PTX in the pegylated TM-SLNs was taken up mainly into reticuloendothelial system showing 8-fold and 3-fold higher levels in liver and spleen, respectively, 8 h after administration compared to PTX in Taxol®. Meanwhile, PTX levels in kidney, heart and lung were not different between two formulations. There were no statistically significant differences in pharmacokinetic parameters. Taken together the results, the pegylated TM-SLNs provided similar circulation compared with commercial formulation, Taxol®.

Anti-allergic components from the peels ofCitrus unshiu

In a bioassay-guided search for anti-allergic compounds from higher plants of Korea, polymethoxyflavones, 3′,4′,5,6,7,8-hexamethoxyflavone (I), 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (II) and 3′,4′,5,7,8,-pentamethoxyflavone (III) have been isolated from the immature peels ofCitrus unshiu. Structures of these compounds were elucidated on the basis of spectroscopic techniques. CompoundsI andII inhibited dose-dependently histamine release from the rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.

Cytotoxic isoquinoline alkaloids from the aerial parts ofCorydalis incisa

Three known isoquinoline alkaloids were isolated from the chloroform-soluble fraction of the methanolic extract of the aerial parts ofCorydalis incisa (Papaveraceae) through repeated column chromatography. Their chemical structures were elucidated as corynoline (1), corynoloxine (2) and 6-oxocorynoline (3) using spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2 and HCT15 tumor cells.

Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice.

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE2 modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE2 in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE2 mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE2 and LPS-stimulated production of PGE2 by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 enhanced production of IL-6, IL-10, and NO but decreased TNF-α by macrophages and augmented IFN-γ, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 also enhanced production of IFN-γ, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE2 synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-α. Indo remarkably inhibited Con A-increased production of IFN-γ, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE2 may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-γ, and NO in pristane-induced lupus mice.