Nanyoung Kim

Five new quassinoids and cytotoxic constituents from the roots of Eurycoma longifolia.

Eurycoma longifolia has been widely used for various traditional medicinal purposes in South-East Asia. In this study, five new quassinoids, eurylactone E (1), eurylactone F (2), eurylactone G (3), eurycomalide D (4), and eurycomalide E (5), along with ten known quassinoids (6-15) were isolated from the roots of E. longifolia. Their structures were determined by extensive spectroscopic methods, including 1D and 2D NMR, and MS spectra data. Among the isolated compounds, 13β-methyl,21-dihydroeurycomanone (6) has been reported as a synthetic derivative. However, it was isolated from the natural product for the first time in this study. The cytotoxic activities of fifteen compounds were evaluated against human lung cancer cell line, A549 and human cervical cancer cell line, HeLa.

Simple self-tuned notch filter in a bio-potential amplifier

INTERFERENCE FROM power lines is a common problem during the measurement of bio-potential signals. Although the construction of a high CMRR differential amplifier, signal and power isolation, and right leg-driven technique (HUNTER and WEBSTER, 1973) are incorporated into the design of a biopotential amplifier, line frequency potentials may appear as normal mode signals, owing to source imbalance and the nonideal properties of the amplifiers and passive components. In a bio-potential amplifier, analogue notch filters have generally been used to remove any remaining interference. To minimise signal loss from the filtering process, the narrowbandwidth property (high Q) of the notch filter is incorporated. However, the frequency of the power lines always deviates from the centre frequency (50 or 60 Hz). As a result, the performance of this type of notch filters is often degraded. If digital methods (LEVKOV et al., 1984; SCHEER, 1987; CHRISTOY and DOTSINSKY, 1988; YAN, 1993) are employed in realtime, digital signal processors or complex logic circuits are required. In this work, a line frequency rejection filter is designed using a switched capacitor filter (SCF) and a phase locked loop (PLL). It is simple and capable of achieving high Q performance under the line frequency variation.

Eucommia ulmoides Oliver extract, aucubin, and geniposide enhance lysosomal activity to regulate ER stress and hepatic lipid accumulation.

Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement and medicinal plant. Here, we examined the potential regulatory effects of Eucommia ulmoides Oliver extracts (EUE) on hepatic dyslipidemia and its related mechanisms by in vitro and in vivo studies. EUE and its two active constituents, aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER) stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes. To determine how EUE diminishes the ER stress response, lysosomal and proteasomal protein degradation activities were analyzed. Although proteasomal activity was not affected, lysosomal enzyme activities including V-ATPase were significantly increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress, secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or its component, aucubin or geniposide. In addition, EUE was determined to regulate hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in rats fed a high-fat diet. Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemia.

Flavonoids isolated from Lespedeza cuneata G. Don and their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated BV-2 microglia cells.

Background: Lespedeza cuneata (Dum. Cours.) G. Don, a perennial legume native to Eastern Asia, has been used therapeutically in traditional Asian medicine to protect the function of liver, kidneys and lungs. However, its effect on inflammatory nitric oxide (NO) production and the active constituents have not yet been explored. Objective: In this study, we investigated the phytochemical constituents of L. cuneata and evaluated their effect on NO production using lipopolysaccharide (LPS)-stimulated BV2 cells. Materials and Methods: The 80% methanol extract of the aerial part of L. cuneata were used for the isolation of flavonoids. The isolated compounds were elucidated by various spectroscopic methods including nuclear magnetic resonance and mass spectrometry spectrometry. To evaluate the effect on inflammatory NO production, LPS-stimulated murine microglia BV-2 cells were used as a screening system. Results: Nine flavonoids were isolated from the aerial parts of L. cuneata. Among the isolated flavonoids, compounds 4, 5, 7 and 9 are reported from the genus Lespedeza for the first time. Moreover, compounds 1 and 6 showed significant inhibitory effects on NO production in LPS-stimulated BV2 cells without cell toxicity. Conclusion: In this study, nine flavonoids were isolated from L. cuneata. Among the compounds, only 1 and 6, which have free hydroxyl groups at both C3 and C7 showed significant inhibitory activity on NO production in LPS-stimulated BV2 cells. These results suggested L. cuneata and its flavonoid constituents as possible candidate for the treatment of various inflammatory diseases.

Determination of Saponins and Flavonoids in Ivy Leaf Extracts Using HPLC-DAD

A new method for the determination of six compounds, chlorogenic acid, rutin, nicotiflorin, hederacoside C, hederasaponin B and α-hederin, in ivy leaf extracts using high-performance liquid chromatography with diode array detector was developed. The chromatographic separation was performed on a YMC Hydrosphere C18 analytical column using a gradient elution of 0.1% phosphoric acid and acetonitrile. The method was validated in terms of specificity, linearity (r(2) > 0.9999), precision [relative standard deviation (RSD) < 0.36%] and accuracy (97.4-103.8%). The limit of detection and limit of quantification were <20.32 and 61.56 ng for all analytes, respectively. The tested compounds were found to be stable in the ivy leaf extract from 0 to 48 h, and the RSD value for each compound was <0.90%. The validated method was successfully applied to quantify all six compounds in a 30% ethanol ivy leaf extract and 13 ivy leaf extract products. The results showed that all the tested products satisfied the minimum requirement for the content of hederacoside C. However, there were some differences between the contents of other constituents.

Muurolane-type sesquiterpenes from marine sponge Dysidea cinerea

Seven new muurolane‐type sesquiterpenes, (4R,5R)‐muurol‐1(6),10(14)‐diene‐4,5‐diol (1), (4R,5R)‐muurol‐1(6)‐ene‐4,5‐diol (2), (4R,5R,10R)‐10‐methoxymuurol‐1(6)‐ene‐4,5‐diol (3), (4S)‐4‐hydroxy‐1,10‐seco‐muurol‐5‐ene‐1,10‐dione (4), (4R)‐4‐hydroxy‐1,10‐seco‐muurol‐5‐ene‐1,10‐dione (5), (6S,10S)‐6,10‐dihydroxy‐7,8‐seco‐2,8‐cyclo‐muurol‐4(5),7(11)‐diene‐12‐oic acid (6), and (6R,10S)‐6,10‐dihydroxy‐7,8‐seco‐2,8‐cyclo‐muurol‐4(5),7(11)‐diene‐12‐oic acid (7) were isolated from the marine sponge Dysidea cinerea. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D‐NMR, 2D‐NMR, and CD spectra as well as by comparing the NMR data with those reported in the literature. Copyright

Rapid Determination of Betulin in Betula platyphylla Outer Bark Using Near-Infrared Spectroscopy

A simple, rapid, and nondestructive method for the determination of betulin in the outer birch bark was developed using near infrared spectroscopy (NIRS). NIRS data of the outer birch bark collected throughout the year was preprocessed and analyzed by principal component analysis, which led to clear discrimination of the samples according to their harvest times. The reference content of betulin, a major constituent of the outer birch bark, was determined using ultra performance liquid chromatography with a diode array detector (UPLC-DAD). The optimized and validated analytical conditions of UPLC-DAD provided better separation and faster analysis time compared to a conventional HPLC method. Betulin content also showed seasonal variation and was higher in the samples collected during the summer season. Partial least squares calibration techniques were employed to estimate the relationship between the NIRS data and betulin contents. The spectral data showed high correlation coefficients (over 0.700) with betulin content. These results indicate that NIRS combined with UPLC can be used to determine the quality and to quantify the betulin content of the outer birch bark.

Ixeris dentata Decreases ER Stress and Hepatic Lipid Accumulation through Regulation of ApoB Secretion

Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.

Oleanane-type saponins from Glochidion glomerulatum and their cytotoxic activities

Eight oleanane-type saponins, glomerulosides A-H, were isolated from leaves of Glochidion glomerulatum. All isolated compounds were evaluated for cytotoxic activity on four human cancer cell lines, A-549, HT-29, OVCAR, and MCF-7. Glomerulosides C and E, which contain a benzoyloxy group at C-22, showed significant cytotoxic activities against the A-549, HT-29, and OVCAR cancer cell lines with IC50 values ranging from 5.9 to 9.8μM. Glomeruloside A showed cytotoxicity on HT-29 and OVCAR cell lines with IC50 values of 7.3 and 6.6μM, respectively. Moreover, glomeruloside B exhibited significant activity on A-549 and HT-29 cancer cell lines with IC50 values of 9.7 and 7.5μM. In contrast, glomerulosides F-H, lacking a benzoyloxy group, showed only moderate cytotoxic activity.

Neuraminidase inhibitory activity by compounds isolated from aerial parts of Rhinacanthus nasutus

Abstract Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of various diseases, such as cancer, fungal infections, herpes virus infections and several types of skin diseases in South-East Asian countries. In this study, eight compounds 1–8 were isolated from the aerial parts of R. nasutus. The structures of compounds were determined by the spectroscopic methods, including 1D and 2D NMR. The isolated compounds were evaluated for neuraminidase inhibitory activity. Several lignans, 2,3-bis[(4-hydroxy-3,5-dimethoxyphenyl)methyl]-1,4-butanediol (5) and 8,8′-bisdihydrosiringenin glucoside (6), significantly inhibited neuraminidase activity, which was comparable to the positive controls, mangiferin and oseltamivir. In addition, a structure-based virtual screening against neuraminidase using bioactive components was demonstrated.