Jae Heon Yang

Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe

Five compounds were isolated from the chloroform-soluble fraction of the methanolic extract of the dried rhizomes of Zingiber officinale (Zingiberaceae) through repeated column chromatography. Their chemical structures were elucidated as 4-, 6-, 8-, and 10-gingerols, and 6-shogaol using spectroscopic analysis. Among the five isolated compounds, 6-shogaol exhibited the most potent cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells. 6-shogaol inhibited proliferation of the transgenic mouse ovarian cancer cell lines, C1 (genotype: p53-/-, c-myc, K-ras) and C2 (genotype: p53-/-, c-myc, Akt), with ED50 values of 0.58 μM (C1) and 10.7 μM (C2).

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.

Acetylcholinesterase inhibitors from the twigs ofvaccinium oldhami miquel

In the course of finding Korean natural products with acetylcholinesterase (AChE) inhibitory activity, we found that a methanolic extract of the twigs ofVaccinium oldhami significantly inhibited AChE. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two compounds, taraxerol (1) and scopoletin (2), as active constituents. These compounds inhibited AChE activity in a dose-dependent manner, and the IC50 values of compounds1 and2 were 33.6 (79 μM) and 10.0 (52 μM) μg/mL, respectively.

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.

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.

Guaiane sesquiterpenoids fromTorilis japonica and their cytotoxic effects on human cancer cell lines

A new compound 2 and two known guaiane-type sesquiterpenoids were isolated from the methylene chloride-soluble fraction of the methanolic extract of the fruits ofTorilis japonica (Umbelliferae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as torilin (1), 11-acetoxy-8-angeloyloxy-1β-hydroxy-4-guaien-3-one (1β-hydroxytorilin,2) and 11-acetoxy-8-angeloyloxy-1α-hydroxy-4-guaien-3-one (1α-hydroxytorilin,3) by spectroscopic analysis. Compounds1–3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.

A new cytotoxic prenylated chalcone fromsophora flavescens

We have isolated a new prenylated chalcone from the roots of Sophora flavescens (Leguminosae). We determined that structure of this compound is 7,9,2’,4’-tetrahydroxy-8-isopentenyl-5-methoxychalcone (1) on the basis of spectroscopic analysis (1D and 2D NMR data). Compound 1 exhibited potent cytotoxicity against human acute promyelocytic (HL60), mouse lymphocytic (L1210) and human histiocytic (U937) leukemia cells.

Farnesyl protein transferase inhibitory components of Polygonum multiflorum

The methanolic extract of the roots of Polygonum multiflorum (Polygonaceae) was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone glycosides, as inhibitors of FPTase. These compounds inhibited the FPTase activity in a dose-dependent manner.

Cytotoxic germacranolide sesquiterpenes from the bark of Magnolia kobus.

A new (3) and three known germacrane-type sesquiterpenoids were isolated from the chloroform-soluble fraction of the methanolic extract of the bark of Magnolia kobus (Magnoliaceae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as costunolide (1), parthenolide (2), isobisparthenolidine (3), and bisparthenolidine (4) by spectroscopic analysis. Compounds 1–4 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.