Jae-Hee Hyun

Fucoidan from Undaria pinnatifida induces apoptosis in A549 human lung carcinoma cells.

Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub‐G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl‐2 expression, but the expression of Bax was increased in a dose‐dependent manner compared with the controls. Furthermore, fucoidan induced caspase‐9 activation, but decreased the level of procaspase‐3. Cleavage of poly‐ADP‐ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down‐regulation of phospho‐p38 expression. In addition, fucoidan resulted in the down‐regulation of phospho‐PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down‐regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway. Copyright

Triterpene compounds isolated from Acer mandshuricum and their anti-inflammatory activity.

In our preliminary screening study on the anti-inflammatory activity, a new triterpene compound, aceranol acetate (1), was isolated along with five known compounds: beta-amyrin acetate (2); glutinol acetate (3); friedelin (4); glutinol (5); (3beta)-d-glucopyranoside-stigmast-5-en-3-yl (6), from the stems and leaves of Acer mandshuricum. The structure of the new triterpene was determined to be 5alpha,6alpha-epidioxy-5beta,6beta-epoxy-9,13-dimethyl-25,26-dinoroleanan-3beta-ol acetate by spectroscopic studies. Compounds 2-6 were isolated from this plant for the first. Five triterpene compounds (1-5) showed significant cytotoxic activity with GI(50) in the range of 11.1-17.9microM, whereas steroid compound (6) exhibited moderate activity against four human cancer cell lines (HL-60, SK-OV-3, A549, and HT-29). Furthermore, the anti-inflammatory effects of compounds 1-6 in the non-cytotoxic concentrations (1-100nM) were evaluated for the inhibitory activity of TNF-alpha secretion in the lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cell line. Among the compounds tested, compound 2 showed the strongest anti-inflammatory activity with the inhibition rate up to 38.40% at the concentration of 100nM, whereas other five compounds (2-6) exhibited moderate activity.

C29 sterols with a cyclopropane ring at C-25 and 26 from the Vietnamese marine sponge Ianthella sp. and their anticancer properties.

Two new C(29) sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1) and 5alpha,6alpha-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese marine sponge Ianthella sp. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compounds 1-3 showed cytotoxic activities on A549, HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC(50) in the range of 8.4-22.6 microM, whereas compounds 1-3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells were treated with the compounds, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. These data supported that the compounds might have potential for leukemia treatment.

Dammarane-type saponins from the flower buds of Panax ginseng and their effects on human leukemia cells

Six dammarane-type saponins, including three new compounds, floralginsenosides Ta-Tc (1-3), and three known, floralginsenoside Td (4), ginsenoside F(1) (5), and ginsenoside F(5) (6), were isolated from the flower buds of Panax ginseng. Floralginsenoside Td (4) was first isolated from natural plant sources. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Compounds 1, 5, and 6 showed cytotoxic activities towards the HL-60 human leukemia cell line with respective IC(50) values of 36.3, 23.2, and 62.4microM. In addition, after the HL-60 cells were treated with these compounds, several apoptosis events, including chromatin condensation and increase in the population of sub-G1 hypodiploid cells, were observed.

6-Hydroxydopamine-Induced PC12 Cell Death is Mediated by MEF2D Down-regulation

Recently, it was reported that in a 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model, neuronal cell death is associated with the cdk5-mediated hyperphosphorylation of myocyte enhancer factor 2 (MEF2), a transcription factor that is critically required for neuronal survival. In the present study, we investigated the possible involvement of cdk5-mediated MEF2D down-regulation on 6-hydroxydopamine (6-OHDA)-induced PC12 cell death. 6-OHDA was found to significantly increase nitric oxide (NO) production and to induce apoptosis in a time-dependent manner in PC12 cells. Furthermore, 6-OHDA was found to markedly reduce MEF2D levels under conditions that could induce PC12 cell apoptosis. In addition, PC12 cell death and MEF2D degradation by 6-OHDA were prevented by the cdk5 inhibitor roscovitine, but roscovitine could not restore the 6-OHDA-induced inactivation of Akt. These results suggest that the cell death and MEF2D degradation caused by 6-OHDA are dependent on cdk5 activity. On the other hand, roscovitine enhanced the 6-OHDA-induced activations of ERK1/2 and JNK, but reduced the 6-OHDA-induced activation of p38. These results suggest that PC12 cell death by 6-OHDA appears to be regulated by the down-regulation of MEF2D via some interaction between cdk5 and MAP kinase.

Promotion effect of Schisandra nigra on the growth of hair

This study was conducted to evaluate the effect of Schisandra nigra, a plant native to Jeju Island, South Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with 85% ethanol (EtOH) extract of S. nigra, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after topical application of the EtOH extract of S. nigra onto the back of C57BL/6 mice every other day, anagen progression of the hair shaft was induced. Moreover, the extract increased both the expression of proliferating cell nuclear antigen (PCNA) in the bulb matrix region and the proliferation of immortalized vibrissa dermal papilla cells. In order to determine the mechanism by which S. nigra promotes hair growth, we examined its relationship with the transforming growth factor-beta2 (TGF-beta2) signal pathway, which is known to be a regulator of catagen induction. When the vibrissa follicles in the anagen phase were treated with S. nigra extract for 7 days, the expression of TGF-beta2 in the bulb matrix region was found to be lower than that of the control follicles that were expected to be in the anagen-catagen transition phase. These results suggest that S. nigra extract has the potential to promote hair growth via down regulation of TGF-beta2 and the proliferation of dermal papilla.

Promotion effect of norgalanthamine, a component of Crinum asiaticum, on hair growth

This study was conducted to evaluate the effect of Crinum asiaticum, a plant native to Jeju Island, Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with a 95% ethanol (EtOH) extract of C. asiaticum, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after daily topical application of the EtOH extract of C. asiaticum onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. Moreover, the extract increased the proliferation of immortalized vibrissa dermal papilla cells. When the vibrissa follicles in the anagen phase were treated with the extract, immunohistochemical analysis revealed that the extract was found to increase the expression of proliferating cell nuclear antigen (PCNA) in the bulb region of the 7-day cultured follicles. In particular, norgalanthamine, a principal of the extract, showed activity that increased the hair-fiber lengths of vibrissa follicles and the proliferation of dermal papilla cells. These results suggest that norgalanthamine, a principal of C. asiaticum, has the potential to promote hair growth via the proliferation of dermal papilla.

Lupane-Type Triterpene Glycosides from the Leaves of Acanthopanax koreanum and Their In Vitro Cytotoxicity

Three new lupane triterpene glycosides, acankoreosides J-L ( 1- 3), were isolated from the leaves of Acanthopanax koreanum. Based on the spectroscopic data, the chemical structures were determined as 3 alpha-hydroxy-20-oxo-30-norlupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 1); 3 alpha,20,29-trihydroxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 2); and (20S)-3 alpha-hydroxy-29,29-dimethoxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 3). Compounds 1- 3 were evaluated for their cytotoxicity and showed moderate activity against four cell lines, A549 (lung), HL-60 (leukemia), MCF-7 (breast), and U937 (leukemia), with IC (50) values of 23.4, 36.5, 22.6, and 18.5 microM for 1; 6.8, 18.6, 23.1, and > 100 microM for 2; and 28.9, 21.8, 11.0, and 27.5 microM for 3, respectively.

Chemical Components from the Vietnamese Soft Coral Lobophytum sp.

Chromatographic separation resulted in the identification of one new squalene derivative, named lobophytene (1), three cembranoid diterpenes (2–4), and two sterols (5 and 6) from the Vietnamese marine soft coral Lobophytum sp. Their structures were identified on the basis of extensive spectroscopic data and comparison of those with reported data. Compounds 1 and 2 showed significant cytotoxic activities against lung (A549) and colon (HT-29) cell lines with IC50 values of 8.2 and 5.6 μM for 1; 5.1 and 1.8 μM for 2, respectively.

A new C29-sterol with a cyclopropane ring at C-25 and 26 from the Vietnamese marine sponge lanthella sp.

One new C29 sterol with a cyclopropane ring at C-25 and C-26, aragusteroketal B (1), and aragusterol B (2) were isolated from the Vietnamese marine sponge Ianthella sp. Their structures were elucidated by extensive spectroscopic analyses. Both 1 and 2 showed moderate cytotoxic activity against MCF-7, SK-Hep-1, and HeLa cell lines with IC50 in the range of 12.8–27.8 μM.