Jung Eun Kwon

Anti-Osteoarthritic Effects of the Litsea japonica Fruit in a Rat Model of Osteoarthritis Induced by Monosodium Iodoacetate

Osteoarthritis (OA) is a degenerative chronic disease that affects various tissues surrounding the joints, such as the subchondral bone and articular cartilage. The onset of OA is associated with uncontrolled catabolic and anabolic remodeling processes of the joints, including the cartilage and subchondral bone, to adapt to local biological and biochemical signals. In this study, we determined whether 70% ethanolic (EtOH) extract of Litsea japonica fruit (LJFE) had beneficial effects on the articular cartilage, including structural changes in the tibial subchondral bone, matrix degradation, and inflammatory responses, in OA by using a rat model of monosodium iodoacetate-induced OA. Our results showed that administration of LJFE increased the bone volume and cross-section thickness, but the mean number of objects per slice in this group was lower than that in the OA control (OAC) group. In addition, the LJFE decreased the expression of inflammatory cytokines. Compared to the OAC group, the group treated with high doses of LJFE (100 and 200 mg/kg) showed a more than 80% inhibition of the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases. Our results suggest that LJFE can be used as a potential anti-osteoarthritic agent.

Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression

Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin.

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(η6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) (2), 5, 8-dioxido-1, 4-naphthoquinonato (3), or 6, 11-dioxido-5, 12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(η6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.

Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages

Three new large hexanuclear metalla-prisms 9–11 incorporating 1,3, 5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by 1H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30±0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 μM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages.

Isoflavones and biotransformed dihydrodaidzein production with in vitro cultured callus of Korean wild arrowroot Pueraria lobata

국내 자생하는 야생칡(Pueraria lobata)은 푸에라린, 다이드진, 다이드제인 등 다양한 이소플라본을 함유하고 있는 주요한 콩과 약용작물이다. 이들 이소플라본은 장내에서 특정 세균과 반응으로 생물전환이 일어나 디하이드로다이드제인, 테트라하이드로다이드제인을 거쳐 약리작용이 타 이소플라본 보다 월등한 이퀄로 물질대사가 이루어지는 것으로 알려져 있다. 본 연구에서는 국내 야생칡으로부터 유도된 캘러스를 이용하여 배양배지, 배양조건 및 배양기간에 따른 캘러스의 증식과 이소플라본의 합성 정도를 구명하고 배양된 캘러스 추출물을 생물전환 능력이 있는 것으로 밝혀진 Pediococcus pentosaceus 균주와의 반응을 통하여 이퀄 전구체인 디하이드로다이드제인의 생합성을 구명하고자 수행되었다. 캘러스의 증식은 광조건에서 1.0 mg/L TDZ과 1.0 mg/L NAA가 첨가된 배지에서 12일 배양했을 때 가장 좋다. 푸에라린 함량은 암조건에서 2.0 mg/L kinetin과 1.0 mg/L NAA가 첨가된 배지에서 16일 배양했을 때 가장 높게 나타났으나, 다이드진과 다이드제인 함량은 처리에 따른 유의한 차이가 나타나지 않았다. 캘러스 추출물을 P. pentosaceus 균주와 반응하여 발효시켰을 때 생물전환에 의해 이퀄의 전구체인 디하이드로다이드제인이 성공적으로 생합성되는 것이 확인되었다. 본 연구의 결과는 국내 야생칡을 대상으로 캘러스의 대량증식을 통한 이퀄의 전구물질인 이소플라본의 대량생산에 기여할 수 있으며, 기내에서 생물전환을 통하여 이퀄을 생산하기 위한 기반이 될 것이다. 【Pueraria lobata, a medicinally important leguminous plant produces various isoflavones including puerarin, daidzin and daidzein which are metabolized to equol via dihydrodaidzein and tetrahydrodaidzein by the bacterial fermentation of natural isoflavone sources in human intestines. In this study, we described callus proliferation and isoflavone production in callus of Korean wild arrowroot and dihydrodaidzein biosynthesis in callus extract fermented with Pediococcus pentosaceus. Proliferation was the best at callus cultured in the medium containing 1.0 mg/L TDZ and 1.0 mg/L NAA at light condition for 12 days. Puerarin was significantly more produced at callus cultured in the medium containing 2.0 mg/L kinetin and 1.0 mg/L NAA at dark condition for 16 days, but daidzin and daidzein were not significant. Callus extract was successfully fermented with P. pentosaceus and dihydrodaidzein, which is one of equol precursors formed by biotransformation, was confirmed to be produced. These results will facilitate mass production of callus and isoflavones as equol precursors from Korean wild arrowroot and can be applied for the production of equol by biotransformation in vitro.】