[Show abstract][Hide abstract] ABSTRACT: It has been reported that alkaloids derived from Coptis chinensis exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-α (C/EBP-α). However, the signaling-based mechanism of the inhibitory role of epiberberine in the early stages of 3T3-L1 adipocyte differentiation is uncharacterized. Here, we show that epiberberine had inhibitory effects on adipocyte differentiation and significantly decreased lipid accumulation by downregulating an adipocyte-specific transcription factor, sterol regulatory element-binding protein-1 (SREBP-1). Furthermore, we observed that epiberberine markedly suppressed the differentiation-mediated phosphorylation of components of both the Raf/mitogen-activated protein kinase 1 (MEK1)/extracellular signal-regulated protein kinase 1/2 (ERK1/2) and AMP-activated protein kinase-α1 (AMPKα)/Akt pathways. In addition, gene expression of fatty acid synthase (FAS) was significantly inhibited by treatment with epiberberine during adipogenesis. These results indicate that the anti-adipogenic mechanism of epiberberine is associated with inhibition of phosphorylation of Raf/MEK1/ERK1/2 and AMPKα/Akt, followed by downregulation of the major transcription factors of adipogenesis, such as PPAR-γ, C/EBP-α, and SREBP-1, and FAS. Taken together, this study suggests that the anti-adipogenic effect of epiberberine is mediated by downregulation of the Raf/MEK1/ERK1/2 and AMPKα/Akt pathways during 3T3-L1 adipocyte differentiation. Moreover, the anti-adipogenic effects of epiberberine were not accompanied by modulation of β-catenin.
Archives of Pharmacal Research 06/2015; DOI:10.1007/s12272-015-0626-3 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of our ongoing isolation of cholinesterase (ChE) inhibitors from natural marine sources, the bioactivity of the ethanolic extracts from 12 Korean seaweeds were screened for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and total reactive oxygen species (ROS) generation. Eisenia bicyclis exhibited promising inhibitory properties against AChE, BChE and total ROS with inhibition percentages (%) of 68.01 ± 1.37, 95.72 ± 3.80, and 73.20 ± 1.82 at concentrations of 25 µg/mL, respectively. Among the different solvent-soluble fractions obtained from the ethanolic extract, the ethyl acetate (EtOAc) fraction was found to cause the most potent scavenging, or inhibitory activities, against 2,2-diphenyl-1-picrylhydrazyl (DPPH), peroxynitrite (ONOO(-)) and total ROS with the respective IC50 values of 2.48 ± 0.01, 8.70 ± 0.06, and 0.81 ± 0.03 µg/mL. Likewise, the EtOAc fraction also exhibited potent inhibitory activities against AChE and BChE with IC50 values of 2.78 ± 0.07 and 3.48 ± 0.32 µg/mL, respectively. Silica gel column chromatography of the EtOAc fraction yielded a phlorotannin, 974-B, based on the comparison with reported (1)H- and (13)C-NMR spectroscopic data. 974-B showed strong scavenging/or inhibitory potential against DPPH, ONOO(-), total ROS, AChE, and BChE with the respective IC50 values of 0.86 ± 0.02, 1.80 ± 0.01, 6.45 ± 0.04, 1.95 ± 0.01, and 3.26 ± 0.08 µM, respectively. These results indicate that the potential of E. bicyclis and its phlorotannin for use in the development of therapeutic or preventive agents of Alzheimer's disease mainly through ChE inhibition and additional antioxidant capacities.
Archives of Pharmacal Research 11/2014; 38(8). DOI:10.1007/s12272-014-0515-1 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The dramatic increase in obesity-related diseases emphasizes the need to elucidate the cellular and molecular mechanisms underlying fat metabolism. Inhibition of adipocyte differentiation has been suggested to be an important strategy for preventing or treating obesity. In our previous study, we characterized an Ecklonia stolonifera extract and non-polar fractions thereof, including dichloromethane and ethyl acetate fractions. We showed that these fractions inhibited adipocyte differentiation and lipid formation/accumulation in 3T3-L1 preadipocytes, as assessed by Oil Red O staining. As part of our ongoing search for anti-obesity agents derived from E. stolonifera, in this work, we characterized five known phlorotannins, including phloroglucinol, eckol, dieckol, dioxinodehydroeckol, and phlorofucofuroeckol A, all of which were isolated from the active ethyl acetate fraction of E. stolonifera. We determined the chemical structures of these phlorotannins through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these phlorotannins for their abilities to inhibit adipogenesis over a range of concentrations (12.5-100μM). Of these five phlorotannins, phloroglucinol, eckol, and phlorofucofuroeckol A significantly concentration-dependently inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability. In addition, the five isolated phlorotannins also significantly reduced the expression levels of several adipocyte marker genes, including proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), although they did so to different extents. These results suggest that the molecular weight of a phlorotannin is an important factor affecting its ability to inhibit adipocyte differentiation and modulate the expression levels of adipocyte marker genes.
[Show abstract][Hide abstract] ABSTRACT: Fucosterol is a sterol metabolite of brown algae and regulates genes involved with cholesterol homeostasis. As a part of our continuous search for anti-obesity agents from natural marine sources, the anti-adipogenic activities of Ecklonia stolonifera and its sterol, fucosterol, were evaluated for the inhibition of adipocyte differentiation and lipid formation. Oil Red O staining was used to evaluate triglyceride contents in 3T3-L1 pre-adipocytes primed by differentiation medium (DM) I and DM II. The methanolic extract of E. stolonifera showed strong anti-adipogenic activity, and was thus fractionated with several solvents. Among the tested fractions, the dichloromethane (CH2Cl2) fraction was found to be the most active fraction, with significant inhibition (40.5 %) of intracellular lipid accumulation at a non-toxic concentration, followed by the ethyl acetate fraction (30.2 %) at the same concentration, while the n-butanol and water fractions did not show inhibitory activity within the tested concentrations. The strong anti-adipogenic CH2Cl2-soluble fraction was further purified by a repeated chromatography to yield fucosterol. Fucosterol reduced lipid contents in a concentration-dependent manner without showing any cytotoxicity. Fucosterol treatment also yielded a decrease in the expression of the adipocyte marker proteins peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) in a concentration-dependent manner. Taken together, these results suggest that fucosterol inhibits expression of PPARγ and C/EBPα, resulting in a decrease of lipid accumulation in 3T3-L1 pre-adipocytes, indicating that the potential use of E. stolonifera and its bioactive fucosterol as an anti-obesity agent.
Archives of Pharmacal Research 09/2013; 37(6). DOI:10.1007/s12272-013-0237-9 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of our continuous search for compounds from natural sources that can treat diabetes and its diabetic complications, in the present work, we investigated the protein tyrosine phosphatase 1B (PTP1B) and rat lens aldose reductase (RLAR) inhibitory activities of the roots of Aralia continentalis. The methanol extract showed a potent inhibitory activity against PTP1B and RLAR. Among the tested fractions, the n-hexane fraction exhibited the highest PTP1B inhibitory activity, while the EtOAc fraction showed highest RLAR inhibitory activity. Bioassayguided fractionation of the active n-hexane and EtOAc soluble fractions resulted in the isolation of the diterpenoids; ent-pimara-8(14),15-diene-19-oic acid (continentalic acid, 1); ent-kaur-16-en-19-oic-acid (kaurenoic acid, 2); ent-pimara-8(14),15-diene-19-ol (3); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (4); 16á-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (5); 17-hydroxy-entkaur-15-en-19-oic acid (6); 15á,16á-epoxy-17-hydroxy-ent-kauran-19-oic acid (7); 16á,17-dihydroxy-ent-kauran-19-oic acid (8); 8á-hydroxy-ent-pimara-15-en-19-ol (9); 4-epirulopezol (10) and 4â-hydroxy-19-nor-(-)-pimara-8(14),15-diene (11), from the n-hexane fraction, and 4-[formy-5-(methoxymethyl)-1H-pyrrol-1-yl] butanoic acid (12); vanillic acid (13); 4-hydroxybenzoic acid (14); protocatechuic acid (15); nicotinic acid (16); aralia cerebroside (17); 5-O-feruloly quinic acid (18) from the EtOAc fraction. Of these, compounds 12∼14, 16 and 18 were isolated from A. continentalis for the first time. Compounds 1∼10 exhibited inhibitory potential against PTP1B, while compounds 12, 17, and 18 were found to be active against RLAR. Taken together, these results clearly demonstrate that the roots of A. continentalis displayed anti-diabetic and antidiabetic properties, which could be further explored to develop therapeutic and preventive agents for the treatment of diabetes and related complications.
Archives of Pharmacal Research 10/2012; 35(10):1771-7. DOI:10.1007/s12272-012-1009-7 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the short-term effect and advantage of transforaminal epidural steroid injection (TFESI) performed using the Kambin's triangle and subpedicular approaches.
Forty-two patients with radicular pain from lumbar spinal stenosis were enrolled. Subjects were randomly assigned to one of two groups. All procedures were performed using C-arm KMC 950. The frequency of complications during the procedure and the effect of TFESI at 2 and 4 weeks after the procedure between the two groups were compared. Short-term outcomes were measured using a visual numeric scale (VNS) and a five-grade scale. Multiple logistic regression analyses were performed to evaluate the relationship between possible outcome predictors (Kambin's triangle or subpedicular approach, age, duration of symptoms and sex) and the therapeutic effect.
VNS was improved 2 weeks after the injection and continued to improve until 4 weeks in both groups. There were no statistical differences in changes of VNS, effectiveness and contrast spread pattern between these two groups. No correlation was found between the other variables tested and therapeutic effect. Spinal nerve pricking occurred in five cases of the subpedicular and in none of the cases of the Kambin's triangle approach (p<0.05).
The Kambin's triangle approach is as efficacious as the subpedicular approach for short-term effect and offers considerable advantages (i.e., less spinal nerve pricking during procedure). The Kambin's triangle approach maybe an alternative method for transforaminal epidural steroid injection in cases where needle tip positioning in the anterior epidural space is difficult.
[Show abstract][Hide abstract] ABSTRACT: The major risk factor of postmenopausal osteoporosis is estrogen deficiency. Hormone replacement therapy is efficacious against osteoporosis, but it induces several significant adverse effects. In this study, therefore, we compared therapeutic potencies of three phytoestrogens: genistein, daidzein, and formononetin. Our result showed that in Saos-2 cells, formononetin and genistein (5 x 10(-7) M) treatment increased alkaline phosphatase activity by 33.0 +/- 5.8% and 21.1 +/- 4.0%. Genistein inhibited osteoclast formation in a dose-dependent manner. In OVX rats, formononetin-treated groups given 1 and 10 mg/kg/day displayed increased trabecular bone areas (TBAs) within the tibia. Genistein- and daidzein-treated groups also displayed increased tibial TBAs. TBAs of the lumbar vertebrae were higher in all treated groups than in the control group. In conclusion, formononetin as well as other isoflavones, such as daidzein and genistein, inhibited bone loss caused by estrogen-deficiency.
Archives of Pharmacal Research 04/2010; 33(4):625-32. DOI:10.1007/s12272-010-0418-8 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present work was to identify products obtained from genistein by ionizing radiation and to enhance the antioxidant properties of genistein through radiation-induced transformation. Genistein dissolved in methanol was irradiated γ-rays at a dose of 100kGy. NMR and (HR) EI-MS spectroscopy were used to identify radiolysis products (GM1 and GM2). We proposed that CH2OH may be implicated in the formation GM1 and GM2 during radiolysis of genistein in methanol. The genistein in methanol solution showed higher DPPH radical scavenging activity after γ-irradiation. Then, the antioxidant activities of radiolysis products were evaluated and compared to those of genistein.
[Show abstract][Hide abstract] ABSTRACT: In this study, we investigated the hypolipidemic effects of Sophora flavescens in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. The MeOH extract and 4 fractions of S. flavescens were administered at doses of 250 and 100 mg/kg body weight, respectively, once a day for 3 d to the poloxamer 407-induced hyperlipidemic rats. Serum lipid levels such as total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were markedly elevated in the poloxamer 407-induced hyperlipidemic control rats, while lipid levels were significantly decreased in the rats administered the MeOH extract or 4 fractions of S. flavescens. In addition, serum high-density lipoprotein-cholesterol (HDL-C) was reduced in the poloxamer 407-induced hyperlipidemic control rats. However, oral administration of both the MeOH extract and 4 fractions significantly increased HDL-C levels. Of the tested fractions, the EtOAc fraction showed the strongest lipid-lowering effect, as well as a high antiatherogenic potential with atherogenic index (A.I.) values of less than 1.92. We also investigated the hypolipidemic effects of the main compounds of the EtOAc fraction, kurarinol and kuraridinol, using the hyperlipidemic and hypercholesterolemic animal models. Here, elevated TC, TG, and LDL-C levels in the poloxamer 407-induced hyperlipidemic and cholesterol-fed rats were significantly reduced after oral administration of the compounds, and HDL-C levels had a significant increase. Furthermore, A.I. values were lowered by administering kurarinol and kuraridinol. In particular, kuraridinol exhibited stronger protective activities against hyperlipidemia than kurarinol. These results suggest that S. flavescens and its constituents may be effective cholesterol-lowering agents and useful for preventing hypercholesterolemic atherosclerosis.
[Show abstract][Hide abstract] ABSTRACT: A new lavandulylated flavonoid, 8-lavandulylkaempferol (1), was isolated from the roots of Sophora flavescens AITON (Leguminosae). The structure of this compound was determined via spectroscopic analysis. Compound 1 was determined to be a scavenger on both 1,1-diphenyl-2-picrylhydrazyl radicals and ONOO-.
Archives of Pharmacal Research 01/2006; 28(12):1333-6. DOI:10.1007/BF02977897 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activity-guided fractionation of the CH2Cl2-soluble fraction of the roots of Sophora flavescens furnished five 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavengers: trans-hexadecyl ferulic acid (1), cis-octadecyl ferulic acid (2), trans-hexadecyl sinapic acid (3), (-)-4-hydroxy-3-methoxy-(6aR,11aR)-8,9-methylenedioxypterocarpan (4) and desmethylanhydroicaritin (8), along with nine known inactive compounds: (-)-maackiain (5), xanthohumol (6), formononetin (7), (2S)-2'-methoxykurarinone (9), (2S)-3beta,7,4'-trihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (10), (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (11), umbelliferone (12), kuraridin (13), and trifolirhizin (14). Compounds 1-4 and 8 exhibited DPPH free radical scavenging effects at IC50 values of 33.01 +/- 0.20, 57.06 +/- 0.16, 39.84 +/- 0.36, 35.83 +/- 0.47, and 18.11 +/- 0.04 microM, respectively. L-Ascorbic acid, when used as a positive control, exhibited an IC50 value of 7.39 +/- 0.01 microM. Compounds 1-4 and 8 also appeared to exert significant scavenging effects on authentic ONOO-, with IC50 values of 5.76 +/- 1.19, 15.06 +/- 1.64, 8.17 +/- 4.97, 1.95 +/- 0.29, and 4.06 +/- 2.41 microM, respectively. Penicillamine (IC50 = 2.36 +/- 0.79 microM) was used as a positive control. In addition, compounds 2, 4, 6, 8, and 10 were isolated from this plant for the first time.
Archives of Pharmacal Research 06/2005; 28(5):534-40. DOI:10.1007/BF02977754 · 1.75 Impact Factor