Eun Young Bae

Isolation of Betulinic Acid, its Methyl Ester and Guaiane Sesquiterpenoids with Protein Tyrosine Phosphatase 1B Inhibitory Activity from the Roots of Saussurea lappa C.B.Clarke

Activity-guided fractionation of a MeOH extract of the roots of Saussurea lappa C.B.Clarke (Compositae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibition assay, led to the isolation of four active constituents: betulinic acid (1), betulinic acid methyl ester (2), mokko lactone (3) and dehydrocostuslactone (4), along with nine inactive compounds. Our findings indicate that betulinic acid (1) and its methyl ester 2, as well as the two guaiane sesquiterpenoids 3 and 4 are potential lead moieties for the development of new PTP1B inhibitors.

Phytochemical mediated gold nanoparticles and their PTP 1B inhibitory activity

Current discovery demonstrates the rapid formation of gold nanoparticles with guavanoic acid a phytochemical of Psidium guajava (Pg). The pharmacological capabilities of the phytochemicals present in the leaves of Pg and their ability to generate gold nanoparticles is presented herein. The new genre of green nanoparticles exhibit remarkable Protein Tyrosine Phosphatase 1B (PTP 1B) inhibitory activity and in vitro stability in various physiological medium including saline, histidine, cysteine, bovine serum albumin (BSA), human serum albumin (HSA) and buffers (pH 5, 7 and 9). It is predicted that this new technology will be felt greatly in several routes of pharmaceuticals.

Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling

Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3‐kinase (PI3‐K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3‐K/Akt and Ras/MAPK pathways cooperate to promote the epithelial–mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3‐K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull‐down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3‐K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3‐K.

Saikosaponin D isolated from Bupleurum falcatum inhibits selectin-mediated cell adhesion.

Three saikosaponins were isolated from the MeOH extract of the roots of Bupleurum falcatum L.: saikosaponins B3 (1); B4 (2); and D (3). Of the three, compound 3 inhibited the interaction of selectins (E, L, and P) and THP-1 cells with IC50 values of 1.8, 3.0 and 4.3 µM, respectively. Also, the aglycone structure 4 of compound 3 showed moderate inhibitory activity on L-selectin-mediated cell adhesion. From these results, we suspect that compound 3 isolated from Bupleurum falcatum roots would be a good candidate for therapeutic strategies to treat inflammation.

Inhibitory Effects of Verrucarin A on Tunicamycin-Induced ER Stress in FaO Rat Liver Cells.

Endoplasmic reticulum (ER) stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat liver cells. In addition, the compound decreased tunicamycin-induced GRP78 promoter activity in a dose dependent manner without inducing significant inhibition of luciferase activity and cell growth for 6 and 12 h. Moreover, the compound decreased the expression of GRP78, CHOP, XBP-1, and suppressed XBP-1, and reduced phosphorylation of IRE1α in FaO rat liver cells. This evidence suggests for the first time that verrucarin A inhibited tunicamycin-induced ER stress in FaO rat liver cells.

Caspase-3 activation as a key factor for HBx-transformed cell death.

Abstract.  Objectives: Nuclear factor‐kappa B (NF‐κB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)‐transformed cells. This study was aimed to find a key target for treatment of HBx‐mediated cancers. Materials and methods: NF‐κB activation, endoplasmic reticulum‐stress (ER‐stress), caspase‐3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF‐κB, proteasome and DNA topoisomerase. Results: Inhibition of NF‐κB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase‐3β (GSK‐3β), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IκBα (S32/36A) mutant plasmid or other NF‐κB inhibitors, 1‐pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor‐1 (Pro1) and MG132 enhanced the HBx‐induced ER‐stress response and the subsequent activation of caspase‐12, ‐9 and ‐3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase‐3 without induction of caspase‐12, and reduced cell proliferation. In addition, CPT‐induced cell death was reversed by pre‐treatment with z‐DEVD, a caspase‐3‐specific inhibitor. Conclusions: Detailed exploitation of the regulators of caspase‐3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx‐transformed hepatocellular carcinoma.

Antioxidative Activities of Sanguisorba officinalis L. in Diabetic Rats

Background: Sanguisorba officinalis has been used in traditional Asian medicine owing to its beneficial effects on various diseases. The purpose of this study was to evaluate the effect of S. officinalis on the antioxidant system of Streptozotocin (STZ) and Alloxan (ALL) induced diabetic rats. Methods and Results: Triglyceride and Low-Density Lipoprotein (LDL)-cholesterol levels decreased in the STZ-induced diabetic groups treated with S. officinalis extract (SOE) compared to the corresponding levels in the control groups. Moreover, in the ALL-induced diabetic groups, SOE reduced triglyceride, LDL-cholesterol, and High-Density Lipoprotein (HDL)-cholesterol levels. Malondialdehyde (MDA) levels decreased significantly in the STZ and ALL-induced groups treated with SOE compared to the corresponding levels in the control group. Further, Glutathione (GSH) levels increased but did not reach statistical significance. The levels of Superoxide Dismutase (SOD) and Glutathione-S-Transferase (GST) showed a tendency to recover with SOE treatment in the STZ and ALL-induced diabetic groups. In addition, Catalase (CAT) levels in the SOE treatment group decreased significantly compared to those in the control group. Conclusions: These results suggest that SOE might be an effective agent in attenuating oxidative stress in diabetic patients by improving blood lipid profiles and inducing the anti-oxidative enzyme systems.