Nam-In Baek

Publications of Nam-In Baek

• Rhus parviflora and its biflavonoid constituent, rhusflavone, induce sleep through the positive allosteric modulation of GABA(A)-benzodiazepine receptors.

  Authors: Sabina Shrestha, Ji-Hae Park, Dae-Young Lee, Jin-Gyeong Cho, Suengmok Cho, Hye-Jin Yang, Hye-Im Yong, Min-Seok Yoon, Dae-Seok Han, Nam-In Baek

  Journal of ethnopharmacology. 05/2012;

  ETHNOPHARMACOLOGICAL RELEVANCE: Rhus parviflora is referred as 'Tintidikah' in traditional medicinal system of south Asia (Ayurveda). It is used in treatment of Vāta vikāra, a condition related toETHNOPHARMACOLOGICAL RELEVANCE: Rhus parviflora is referred as 'Tintidikah' in traditional medicinal system of south Asia (Ayurveda). It is used in treatment of Vāta vikāra, a condition related to neurological complications as well as cure for stomach disorders. MATERIALS AND METHODS: Dried and powdered fruits of R. parviflora were extracted with 80% aqueous methanol (RPME). The concentrated extract was successively partitioned with distilled water, ethyl acetate, and n-butanol. All extracts, as well as isolated biflavonoids from R. parviflora, were evaluated for their affinity to the benzodiazepine binding site of GABA(A) receptor. The sedative-hypnotic effects of the fractions were evaluated by measuring sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of the extract fractions. RESULTS: Oral administration of RPME (125mg/kg, 250mg/kg, 500mg/kg, and 1000mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in mice treated with pentobarbital. The methanol extract produced a hypnotic effect that was fully blocked by (3)H-Ro 15-1788 flumazenil (FLU). Further, among the solvent fractions, the ethyl acetate fraction exhibited significant activity. Among the isolated compounds, biflavonoids mesuaferrone B (1), rhusflavone (3), and agathisflavone (4) competitively inhibited FLU binding with a K(i) of 0.280μM, 0.045μM, and 0.091μM, respectively. In addition, analysis of the sedative-hypnotic effects of rhusflavone, as well as those of the ethyl acetate, n-butanol, and distilled water fractions revealed that the modulation of both the ethyl acetate fraction and biflavonoid rhusflavone (3) are the most potent in inducing sleep. CONCLUSION: The presence of conjugated ketone and C6-C8″ biflavonoid linkage in rhusflavone may be responsible for BZD-site of the GABA(A) leading to decrease in sleep latency and increase sleep duration.

• Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol.

  Authors: Suengmok Cho, Ji-Hae Park, Ae Nim Pae, Daeseok Han, Dongsoo Kim, Nam-Chul Cho, Kyoung Tai No, Hyejin Yang, Minseok Yoon, Changho Lee, Makoto Shimizu, Nam-In Baek

  Bioorganic & medicinal chemistry. 04/2012;

  Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurologicalLicorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurological properties such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE was completely inhibited by flumazenil, which is a well-known γ-aminobutyric acid type A-benzodiazepine (GABA(A)-BZD) receptor antagonist, similar to other GABA(A)-BZD receptor agonists (e.g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [(3)H] flumazenil binding to the GABA(A)-BZD receptors in rat cerebral cortex membrane with a binding affinity (K(i)) of 1.63μM. The molecular structure and pharmacophore model of glabrol and liquiritigenin indicate that the isoprenyl groups of glabrol may play a key role in binding to GABA(A)-BZD receptors. Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25, and 50mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid glabrol induce sleep via a positive allosteric modulation of GABA(A)-BZD receptors.

• Standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal induces apoptosis via mitochondrial pathway in human cervical cancer HeLa cells.

  Authors: Hye-Kyung Ju, Heon-Woo Lee, Kyung-Sook Chung, Jung-Hye Choi, Jin-Gyeong Cho, Nam-In Baek, Hae-Gon Chung, Kyung-Tae Lee

  Journal of ethnopharmacology. 03/2012;

  ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia princeps Pampanini is widely used in Eastern traditional medicine for the treatment of circulatory disorders, such as, dysmenorrhea, hematuria, hemorrhoids,ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia princeps Pampanini is widely used in Eastern traditional medicine for the treatment of circulatory disorders, such as, dysmenorrhea, hematuria, hemorrhoids, and inflammation, and is also used to treat chronic conditions, such as, cancers, ulcers, and digestive disorders. AIM OF THE STUDY: The purpose of this study is to investigate the effect of a standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal (FRAP) on the induction of apoptosis and the molecular mechanism involved in human cervical cancer HeLa cells. MATERIALS AND METHODS: Human cervical cancer HeLa cells were treated with FRAP and apoptosis was detected by cell morphologic observation, annexin-V-PI staning and western blot analysis on the expression of protein associated with cell death. RESULTS: FRAP led to the cleavages of caspase-3, -8, and -9 and the cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells. Caspase-3 inhibitor (z-DEVD-fmk), caspase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD), and broad caspase inhibitor (z-VAD-fmk) significantly suppressed the FRAP-induced accumulation of annexin V positive cells. Furthermore, it was found that FRAP caused a loss of mitochondrial membrane potential (MMP) and the release of cytochrome c to the cytosol. Furthermore, the overexpression of Bcl-xL significantly prevented FRAP-induced apoptosis, MMP changes, and the activations of caspase-3, -8, and -9. Interestingly, pretreatment with caspase-8 inhibitor significantly reduced the FRAP-induced activation of caspase-3 but not that of caspase-9, whereas the caspase-3 inhibitor, z-DEVD-fmk, markedly attenuated the FRAP-induced activation of caspase-8. In BALB/c(nu/nu) mice bearing a HeLa xenograft, FRAP dosed at 25 or 50mg/kg significantly inhibited tumor growth. CONCLUSION: Our results indicate caspase-mediated activation of the mitochondrial death pathway plays a critical role in the FRAP-induced apoptosis of HeLa cells and that FRAP inhibits the in vivo tumor growth of HeLa xenograft mice.

• Inhibitory effects of actinidiamide from Actinidia polygama on allergy and inflammation.

  Authors: Myun-Ho Bang, In-Gyeong Chae, Eun-Ju Lee, Nam-In Baek, Yoon-Su Baek, Dae-Young Lee, In-Seon Lee, Sam-Pin Lee, Seun-Ah Yang

  Bioscience, biotechnology, and biochemistry. 02/2012; 76(2):289-93.

  Actinidia polygama Max. was subjected to supercritical fluid extraction (SFE), and the resulting ethanol extract of marc (SFEM) was subjected to sequential fractionation with various solvents. EachActinidia polygama Max. was subjected to supercritical fluid extraction (SFE), and the resulting ethanol extract of marc (SFEM) was subjected to sequential fractionation with various solvents. Each extract and fraction was assayed for anti-inflammatory effect. The ethyl acetate fraction (EtOAc) contained the highest level (70.8% inhibition) of anti-inflammatory activity. In order to identify the active constituents, the EtOAc fraction was further fractionated by silica gel and ODS column chromatography. By activity-guided fractionation, an active ceramide was identified as the anti-inflammatory component, and its structure was determined by NMR and MS analysis. The novel ceramide was named actinidiamide, and was found significantly to inhibit nitric oxide (NO) production (30.6% inhibition at 1 µg/mL) in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells and β-hexosaminidase release (91.8% inhibition at 1 µg/mL) in IgE-sensitized RBL-2H3 cells. Thus the presence of actinidiamide conveys allergy and inflammation treatment ability to A. polygama.

• 3-O-Acetyloleanolic Acid Induces Apoptosis in Human Colon Carcinoma Hct-116 Cells.

  Authors: Ki Hyun Yoo, Jong-Hwa Park, En Ji Cui, Kyung Il Kim, Joo Yun Kim, Jiyoung Kim, Seong Gil Hong, Nam In Baek, In Sik Chung

  Phytotherapy research : PTR. 02/2012;

  The cytotoxic effect of 3-O-acetyloleanolic acid, an oleanolic acid derivative isolated from the seeds of Vigna sinensis K., was investigated in human colon carcinoma HCT-116 cells.The cytotoxic effect of 3-O-acetyloleanolic acid, an oleanolic acid derivative isolated from the seeds of Vigna sinensis K., was investigated in human colon carcinoma HCT-116 cells. 3-O-acetyloleanolic acid dose-dependently inhibited the viability of HCT-116 cells. Apoptosis was characterized by detection of cell surface annexin V and sub-G1 apoptotic cell populations. The number of immunostained cells with annexin V-FITC was increased after treatment with 3-O-acetyloleanolic acid. The sub-G1 cell population was also increased. Expression of TRAIL-mediated apoptosis signaling-related death receptor DR5 was increased in 3-O-acetyloleanolic acid-treated HCT-116 cells. Activation of caspase-8 and caspase-3, critical mediators of extrinsic apoptosis signaling, was also increased by 3-O-acetyloleanolic acid. The results indicate that 3-O-acetyloleanolic acid induces apoptosis in HCT-116 cells mediated by an extrinsic apoptosis signaling cascade via up-regulation of DR5. Copyright © 2012 John Wiley & Sons, Ltd.

• High-yield enzymatic bioconversion of hydroquinone to α-arbutin, a powerful skin lightening agent, by amylosucrase.

  Authors: Dong-Ho Seo, Jong-Hyun Jung, Suk-Jin Ha, Hyun-Kug Cho, Dong-Hyun Jung, Tae-Jip Kim, Nam-In Baek, Sang-Ho Yoo, Cheon-Seok Park

  Applied microbiology and biotechnology. 02/2012;

  α-Arbutin (α-Ab) is a powerful skin whitening agent that blocks epidermal melanin biosynthesis by inhibiting the enzymatic oxidation of tyrosine and L: -3,4-dihydroxyphenylalanine (L: -DOPA). α-Abα-Arbutin (α-Ab) is a powerful skin whitening agent that blocks epidermal melanin biosynthesis by inhibiting the enzymatic oxidation of tyrosine and L: -3,4-dihydroxyphenylalanine (L: -DOPA). α-Ab was effectively synthesized from hydroquinone (HQ) by enzymatic biotransformation using amylosucrase (ASase). The ASase gene from Deinococcus geothermalis (DGAS) was expressed and efficiently purified from Escherichia coli using a constitutive expression system. The expressed DGAS was functional and performed a glycosyltransferase reaction using sucrose as a donor and HQ as an acceptor. The presence of a single HQ bioconversion product was confirmed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The HQ bioconversion product was isolated by silica gel open column chromatography and its chemical structure determined by (1)H and (13) C nuclear magnetic resonance (NMR). The product was determined to be hydroquinone-O-α-D: -glucopyranoside with a glucose molecule linked to HQ through an α-glycosidic bond. However, the production yield of the transfer reaction was significantly low (1.3%) due to the instability of HQ in the reaction mixture. The instability of HQ was considerably improved by antioxidant agents, particularly ascorbic acid, implying that HQ is labile to oxidation. A maximum yield of HQ transfer product of 90% was obtained at a 10:1 molar ratio of donor (sucrose) and acceptor (HQ) molecules in the presence of 0.2 mM ascorbic acid.

• Structural and quantitative analysis of antioxidant and low-density lipoprotein-antioxidant flavonoids from the grains of sugary rice.

  Authors: Dae-Young Lee, Sabina Shrestha, Woo Duck Seo, Min-Ho Lee, Tae-Sook Jeong, Jun Hyun Cho, You Chun Song, Hang Won Kang, Yeong-Deok Rho, Nam-In Baek

  Journal of medicinal food. 02/2012; 15(4):399-405.

  Abstract Grains of sugary rice were extracted with 80% aqueous methanol, and the concentrated extracts were successively partitioned using ethyl acetate, n-butanol, and water. From the n-butanolAbstract Grains of sugary rice were extracted with 80% aqueous methanol, and the concentrated extracts were successively partitioned using ethyl acetate, n-butanol, and water. From the n-butanol fractions, four flavonoid glycosides were isolated through repeated silica gel, octadecyl silica gel, and Sephadex LH-20 column chromatographies. Based on the nuclear magnetic resonance, mass spectrometry, and infrared spectroscopic data, the chemical structures of the compounds were determined to be taxifolin-7-O-β-d-glucopyranoside (1), hyperin (2), isoquercitrin (3), and quercetin gentiobioside (4). These compounds were isolated from the grains of sugary rice for the first time. All isolated compounds were tested for antioxidant activity and low-density lipoprotein (LDL)-antioxidative activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and LDL assays. Compound 1 exhibited a strong scavenging effect on DPPH, with a 50% inhibition concentration (IC(50)) value of 8.1 μM, and also inhibited LDL oxidation with an IC(50) value of 40.0±20 μM. A simple and efficient high-performance liquid chromatography/diode array detection method for the simultaneous determination of the four bioactive flavonoids (1-4) has been developed and applied to their content determination in the sugary rice. The grains were extracted by 80% methanol, and the contents of 1, 2, 3, and 4 were determined to be 1.12±0.045, 0.65±0.011, 0.68±0.032, and 0.89±0.021 mg/g, respectively.

• Lignans from the flowers of Osmanthus fragrans var. aurantiacus and their inhibition effect on NO production.

  Authors: Do-Gyeong Lee, Sang-Min Lee, Myun-Ho Bang, Hee-Jung Park, Tae-Hoon Lee, Yun-Hee Kim, Ji-Young Kim, Nam-In Baek

  Archives of pharmacal research. 12/2011; 34(12):2029-35.

  A new lignan, (7R,7'R,8R,8'R)-8-hydroxypinoresinol 8-O-β-D-glucopyranoside 4'-methyl ether (7), was isolated from the flowers of Osmanthus fragrans var. aurantiacus along with six known lignans:A new lignan, (7R,7'R,8R,8'R)-8-hydroxypinoresinol 8-O-β-D-glucopyranoside 4'-methyl ether (7), was isolated from the flowers of Osmanthus fragrans var. aurantiacus along with six known lignans: (+)-phillygenin (1), phillyrin (2), (-)-phillygenin (3), (-)-epipinoresinol-β-D-glucoside (4), taxiresinol (5), and (-)-olivil (6). The structure of the new compound was elucidated on the basis of 1D- and 2D-NMR spectroscopic analysis and specific rotation data. The compounds isolated from the flowers of O. fragrans var. aurantiacus were evaluated for inhibitory activities on nitric oxide production in lipopolysaccharide-stimulated macrophage RAW 264.7 cells. (+)-Phillygenin (1), phillyrin (2), and (-)-phillygenin (3) exerted the strongest inhibitory activities on NO production with IC(50) values of 25.5, 18.9, and 25.5 μM, respectively. These compounds may prove beneficial in the development of natural agents for prevention and treatment of inflammatory diseases.

• Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects.

  Authors: Suengmok Cho, Sojin Kim, Zhenhua Jin, Hyejin Yang, Daeseok Han, Nam-In Baek, Jinho Jo, Chang-Won Cho, Ji-Hae Park, Makoto Shimizu, Young-Ho Jin

  Biochemical and biophysical research communications. 09/2011; 413(4):637-42.

  Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolyticIsoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 μM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 μM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors.

• Indole-containing fractions of Brassica rapa inhibit inducible nitric oxide synthase and pro-inflammatory cytokine expression by inactivating nuclear factor-κB.

  Authors: Ji-Sun Shin, Chang Hyeon Yun, Young-Wuk Cho, Nam-In Baek, Myung-Sook Choi, Tae-Sook Jeong, Hae-Gon Chung, Kyung-Tae Lee

  Journal of medicinal food. 08/2011; 14(12):1527-37.

  In an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the anti-inflammatory potential of the indole-containing fraction from the roots of Brassica rapaIn an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the anti-inflammatory potential of the indole-containing fraction from the roots of Brassica rapa (IBR) (Family Brassicaceae) and the underlying mechanisms. Initially, we examined the inhibitory effect of IBR on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effects. IBR was found to concentration-dependently reduce the productions of nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced macrophages. Consistent with these findings, IBR suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS, TNF-α, and IL-6 at the mRNA level. Furthermore, IBR attenuated LPS-induced DNA-binding activities of nuclear factor-κB (NF-κB), and this was accompanied by a parallel reduction in the degradation and phosphorylation of inhibitory κBα and, consequently, by a reduction in the nuclear translocation of the p65 subunit of NF-κB. In addition, treatment with IBR inhibited carrageenan-induced paw edema in rats and acetic acid-induced writing response in mice. Taken together, our data suggest that the expressional inhibitions of iNOS, TNF-α, and IL-6 caused by an attenuation of NF-κB activation are responsible for the anti-inflammatory and antinociceptive activity of IBR.

• Eupatilin, a dietary flavonoid, induces G2/M cell cycle arrest in human endometrial cancer cells.

  Authors: Jung-Hoon Cho, Jong-Gyu Lee, Yeong-In Yang, Ji-Hyun Kim, Ji-Hye Ahn, Nam-In Baek, Kyung-Tae Lee, Jung-Hye Choi

  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 08/2011; 49(8):1737-44.

  This study is the first to investigate the antiproliferative effect of eupatilin in human endometrial cancer cells. Eupatilin, a naturally occurring flavonoid isolated from Artemisia princeps, hasThis study is the first to investigate the antiproliferative effect of eupatilin in human endometrial cancer cells. Eupatilin, a naturally occurring flavonoid isolated from Artemisia princeps, has anti-inflammatory, anti-oxidative, and anti-tumor activities. In the present study, we investigated the potential effect of eupatilin on cell growth and its molecular mechanism of action in human endometrial cancer cells. Eupatilin was more potent than cisplatin in inhibiting cell viability in the human endometrial cancer cell lines Hec1A and KLE. Eupatilin showed relatively low cytotoxicity in normal human endometrial cells HES and HESC cells when compared to cisplatin. Eupatilin induced G2/M phase cell cycle arrest in a time- and dose-dependent manner, as indicated by flow cytometry analysis. In addition, treatment of Hec1A cells with eupatilin resulted in a significant increase in the expression of p21(WAF1/CIP1) and in the phosphorylation of Cdc25C and Cdc2. Knockdown of p21 using specific siRNAs significantly compromised eupatilin-induced cell growth inhibition. Interestingly, levels of mutant p53 in Hec1A cells decreased markedly upon treatment with eupatilin, and p53 siRNA significantly increased p21 expression. Moreover, eupatilin modulated the phosphorylation of protein kinases ERK1/2, Akt, ATM, and Chk2. These results suggest that eupatilin inhibits the growth of human endometrial cancer cells via G2/M phase cell cycle arrest through the up-regulation of p21 by the inhibition of mutant p53 and the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway.

• Biosynthesis of (+)-catechin glycosides using recombinant amylosucrase from Deinococcus geothermalis DSM 11300.

  Authors: Hyun-Kug Cho, Hee-Hang Kim, Dong-Ho Seo, Jong-Hyun Jung, Ji-Hae Park, Nam-In Baek, Myo-Jeong Kim, Sang-Ho Yoo, Jaeho Cha, Young-Rok Kim, Cheon-Seok Park

  Enzyme and microbial technology. 07/2011; 49(2):246-53.

  Amylosucrase (ASase, EC 2.4.1.4) is a glucosyltransferase that hydrolyzes sucrose into glucose and fructose and produces amylose-like glucan polymers from the released glucose. (+)-Catechin is aAmylosucrase (ASase, EC 2.4.1.4) is a glucosyltransferase that hydrolyzes sucrose into glucose and fructose and produces amylose-like glucan polymers from the released glucose. (+)-Catechin is a plant polyphenolic metabolite having skin-whitening and antioxidant activities. In this study, the ASase gene from Deinococcus geothermalis (dgas) was expressed in Escherichia coli, while the recombinant DGAS enzyme was purified using a glutathione S-transferase fusion system. The (+)-catechin glycoside derivatives were synthesized from (+)-catechin using DGAS transglycosylation activity. We confirmed the presence of two major transglycosylation products using TLC. The (+)-catechin transglycosylation products were isolated using silica gel open column chromatography and recycling-HPLC. Two (+)-catechin major transfer products were determined through (1)H and (13)C NMR to be (+)-catechin-3'-O-α-D-glucopyranoside with a glucose molecule linked to (+)-catechin and (+)-catechin-3'-O-α-D-maltoside with a maltose linked to (+)-catechin. The presence of (+)-catechin maltooligosaccharides in the DGAS reaction was also confirmed via recycling-HPLC and enzymatic analysis. The effects of various reaction conditions (temperature, enzyme concentration, and molar ratio of acceptor and donor) on the yield and type of (+)-catechin glycosides were investigated.

• Flavonoids from silkworm droppings and their promotional activities on heme oxygenase-1.

  Authors: Ji-Hae Park, Dae-Young Lee, Pyeong Yun, Seung-Woo Yeon, Jong Hee Ko, Yong-Soon Kim, Nam-In Baek

  Journal of Asian natural products research. 04/2011; 13(4):377-82.

  A new flavane glucoside, 7,2'-dihydroxy-8-hydroxyethyl-4'-methoxyflavane-2'-O-β-d-glucopyranoside (3), along with three known flavonoids, 7,2'-dihydroxy-8-prenyl-4'-methoxyflavane (1), euchrenoneA new flavane glucoside, 7,2'-dihydroxy-8-hydroxyethyl-4'-methoxyflavane-2'-O-β-d-glucopyranoside (3), along with three known flavonoids, 7,2'-dihydroxy-8-prenyl-4'-methoxyflavane (1), euchrenone a(7) (2), and 7,2'-dihydroxy-8-prenyl-4'-methoxy-2'-O-β-d-glucopyranosylflavane (4), was isolated from silkworm droppings. The structures of the compounds were elucidated on the basis of 1D and 2D NMR spectroscopic analyses and optical rotational characteristics. The compounds isolated from silkworm droppings were evaluated for their effects on heme oxygenase-1 (HO-1) activity. Compounds 1 and 3 increased the expression of HO-1 in HepG2 cells. HO-1 is an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron, and biliverdin, all of which are involved in the suppression of inflammatory mediators.

• Isolation of megastigmane sesquiterpenes from the silkworm (Bombyx mori L.) droppings and their promotion activity on HO-1 and SIRT1.

  Authors: Ji-Hae Park, Do-Gyeong Lee, Seung-Woo Yeon, Hyuk-Sang Kwon, Jong-Hee Ko, Dong-Jin Shin, Han-Sol Park, Yong-Soon Kim, Myun-Ho Bang, Nam-In Baek

  Archives of pharmacal research. 04/2011; 34(4):533-42.

  The silkworm (Bombyx mori L.) droppings were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned in succession with EtOAc, n-BuOH, and H(2)O. From the EtOAc fraction, fiveThe silkworm (Bombyx mori L.) droppings were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned in succession with EtOAc, n-BuOH, and H(2)O. From the EtOAc fraction, five megastigmane sesquiterpenes were isolated through repeated silica gel and ODS column chromatography. According to the results of spectroscopic data, such as NMR, MS, and IR, the chemical structures of the isolated compounds were determined as (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (1), (S)-dehydrovomifoliol (2), (6R,7E,9R) -9-hydroxy-4,7-megastigmadien-3-one (3), (3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (4), (6R,9R)-9-hydroxy-4-megastigmen-3-one (5). Compounds 2 through 5 were isolated for the first time from silkworm droppings. GC/MS analysis indicated silkworm powder contained compound 3, and mulberry leaves contained compound 4. Compounds 1 and 5 increased the expression of heme oxygenase-1 and SIRT1 in HepG2 and HEK239 cells, respectively. Heme oxygenase-1 is considered to be an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron and biliverdin, while SIRT1 is the mammalian homologue of the yeast silent information regulator (Sir)-2, which are involved in the suppression of inflammatory mediators or factors that may be used to improve atopy-related symptoms.

• Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.

  Authors: Ji-Sun Shin, Young-Su Noh, Yong Sup Lee, Young-Wuk Cho, Nam-In Baek, Myung-Sook Choi, Tae-Sook Jeong, Eunkyung Kang, Hae-Gon Chung, Kyung-Tae Lee

  British journal of pharmacology. 03/2011; 164(1):145-58.

  Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolatedBrassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS. The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-α, IL-6 and IL-1β were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-κB activation and its pathways were investigated by electrophoretic mobility shift assay, reporter gene and Western blot assays. In addition, the in vivo anti-inflammatory effects of arvelexin were evaluated in endotoxaemia induced with LPS. Promoter assays for iNOS and COX-2 revealed that arvelexin inhibited LPS-induced NO and prostaglandin E(2) production through the suppression of iNOS and COX-2 at the level of gene transcription. In addition, arvelexin inhibited NF-κB-dependent inflammatory responses by modulating a series of intracellular events of IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signalling. Moreover, arvelexin inhibited IKKβ-elicited NF-κB activation as well as iNOS and COX-2 expression. Serum levels of NO and inflammatory cytokines and mortality in mice challenged injected with LPS were significantly reduced by arvelexin. Arvelexin down-regulated inflammatory iNOS, COX-2, TNF-α, IL-6 and IL-1β gene expression in macrophages interfering with the activation of IKKβ and p38 mitogen-activated protein kinase, and thus, preventing NF-κB activation.

• A glycosidic spinasterol from Koreana stewartia promotes procollagen production and inhibits matrix metalloproteinase-1 expression in UVB-irradiated human dermal fibroblasts.

  Authors: Tae Hoon Lee, Sang Min Lee, Dae-Young Lee, Youngsook Son, Dae Kyun Chung, Nam-In Baek, Jiyoung Kim

  Biological & pharmaceutical bulletin. 01/2011; 34(5):768-73.

  Methanol extract of Koreana stewartia leaves (SKE) stimulated collagen production in ultraviolet-B (UVB)-irradiated human fibroblast cells. An active compound was isolated from SKE by successiveMethanol extract of Koreana stewartia leaves (SKE) stimulated collagen production in ultraviolet-B (UVB)-irradiated human fibroblast cells. An active compound was isolated from SKE by successive partitioning and chromatography, and the chemical structure was determined to be 3-O-β-D-glucopyranosylspinasterol (spinasterol-Glc) by spectroscopic characterization. Spinasterol-Glc increased collagen production in the supernatant of UVB-irradiated dermal fibroblast cell cultures in a dose-dependent manner. The effects of spinasteol-Glc on expression of procollagen and matrix metalloproteinase-1 (MMP-1) were further evaluated. We found that the compound stimulated collagen production in UVB-treated fibroblasts than in vehicle-treated control cells by about 3-fold. In addition, we also demonstrate that the compound increased the mRNA and protein levels of procollagen in UVB-treated fibroblast cells, while it inhibited expression of MMP-1. These results indicate that spinasterol-Glc protects fibroblast cells from the adverse effects of UV radiation via stimulation of procollagen synthesis as well as inhibition of MMP-1 expression. Spinasterol-Glc may be useful in the future development of therapeutic and cosmetic applications.

• In vitro metabolism of jaceosidin and characterization of cytochrome P450 and UDP-glucuronosyltransferase enzymes in human liver microsomes.

  Authors: Won Young Song, Hye Young Ji, Nam-In Baek, Tae-Sook Jeong, Hye Suk Lee

  Archives of pharmacal research. 12/2010; 33(12):1985-96.

  Jaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. JaceosidinJaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. Jaceosidin was metabolized to jaceosidin glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This study characterized the human liver cytochrome P450 (CYP) and UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of jaceosidin. CYP1A2 was identified as the major enzyme responsible for the formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the basis of a combination of correlation analysis and experiments including immuno-inhibition, chemical inhibition in human liver microsomes, and metabolism by human cDNA-expressed CYP enzymes. Jaceosidin glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic CYP1A2, UGT1A1, and UGT1A7 responsible for the metabolism of jaceosidin or by the coadministration of relevant CYP1A2 or UGT inhibitors or inducers.

• Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice.

  Authors: Hien-trung Trinh, Eun-ha Joh, Ho-young Kwak, Nam-in Baek, Dong-hyun Kim

  Acta pharmacologica Sinica. 06/2010; 31(6):718-24.

  To explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB). Baicalin was anaerobically incubatedTo explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB). Baicalin was anaerobically incubated with human fecal microflora, and its metabolites, baicalein and oroxylin A, were isolated. The inhibitory effect of baicalin and its metabolites was accessed in histamine- or compound 48/80-induced scratching behavior in mice. Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of 40.2+/-26.2 and 1.2+/-1.1 nmol.h(-1).mg(-1) wet weight of human fecal microflora, respectively. Baicalin (20, 50 mg/kg) showed more potent inhibitory effect on histamine-induced scratching behavior when orally administered than intraperitoneally. In contrast, baicalein and oroxylin A had more potent inhibitory effect when the intraperitoneally administered. The anti-scratching behavior activity of oral baicalin and its metabolites was in proportion to their inhibition on histamine-induced increase of vascular permeability with oroxylin A more potent than baicalein and baicalin. In Magnus test using guinea pig ileum, oroxylin A is more potent than baicalein and baicalin in inhibition of histamine-induced contraction. The anti-scratching behavioral effect of oral baicalin was significantly reduced when oral antibiotics were simultaneously administered, whereas the effect of baicalein and oroxylin A were not affected. Oral baicalin may be metabolized by intestinal microflora into baicalein and oroxylin A, which ameliorate pruritic reactions through anti-histamine action.

• Ethanolic extracts of Brassica campestris spp. rapa roots prevent high-fat diet-induced obesity via beta(3)-adrenergic regulation of white adipocyte lipolytic activity.

  Authors: Sojin An, Jang-Il Han, Min-Jung Kim, Ji-Seon Park, Jong-Min Han, Nam-In Baek, Hae-Gon Chung, Myung-Sook Choi, Kyung-Tae Lee, Tae-Sook Jeong

  Journal of medicinal food. 04/2010; 13(2):406-14.

  The influence of ethanolic extracts of Brassica campestris spp. rapa roots (EBR) on obesity was examined in imprinting control region (ICR) mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes.The influence of ethanolic extracts of Brassica campestris spp. rapa roots (EBR) on obesity was examined in imprinting control region (ICR) mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. The ICR mice used were divided into regular diet, HFD, EBR (50 mg/kg/day EBR administered orally), and orlistat (10 mg/kg/day orlistat administered orally) groups. The molecular mechanism of the anti-obesity effect of EBR was investigated in 3T3-L1 adipocytes as well as in HFD-fed ICR mice. In the obese mouse model, both weight gain and epididymal fat accumulation were highly suppressed by the daily oral administration of 50 mg/kg EBR for 8 weeks, whereas the overall amount of food intake was not affected. EBR treatment induced the expression in white adipocytes of lipolysis-related genes, including beta(3)-adrenergic receptor (beta(3)-AR), hormone-sensitive lipase (HSL), adipose triglyceride lipase, and uncoupling protein 2. Furthermore, the activation of cyclic AMP-dependent protein kinase, HSL, and extracellular signal-regulated kinase was induced in EBR-treated 3T3-L1 cells. The lipolytic effect of EBR involved beta(3)-AR modulation, as inferred from the inhibition by the beta(3)-AR antagonist propranolol. These results suggest that EBR may have potential as a safe and effective anti-obesity agent via the inhibition of adipocyte lipid accumulation and the stimulation of beta(3)-AR-dependent lipolysis.

• Simultaneous suppression of three genes related to brassinosteroid (BR) biosynthesis altered campesterol and BR contents, and led to a dwarf phenotype in Arabidopsis thaliana.

  Authors: Ho Yong Chung, Shozo Fujioka, Sunghwa Choe, Soyoun Lee, Youn Hyung Lee, Nam In Baek, In Sik Chung

  Plant cell reports. 02/2010; 29(4):397-402.

  We generated transgenic lines of Arabidopsis thaliana with an RNA interference construct that expressed hairpin double-stranded RNA for DET2:DWF4:SMT2 to induce sequence-specific RNA silencing. InWe generated transgenic lines of Arabidopsis thaliana with an RNA interference construct that expressed hairpin double-stranded RNA for DET2:DWF4:SMT2 to induce sequence-specific RNA silencing. In transgenic plants, expressions of DET2, DWF4, and SMT2 were simultaneously reduced, and the campesterol content was increased by up to 420% compared to the level in the wild-type plant. Triple knock-down of the DET2, DWF4, and SMT2 enzymes also resulted in reduction of brassinosteroid (BR)-specific biosynthesis intermediates. Transgenic plants harboring the RNA interference construct displayed a semi-dwarf phenotype due to altered development. Our findings indicate that redesigning of plant architecture is possible through simultaneous suppression of multiple genes involved in BR biosynthesis.