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Bhimanagouda S Patil - One of the best experts on this subject based on the ideXlab platform.
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nanoformulation and characterization of Nomilin with different poly lactic co glycolic acid resomers and surfactants for the enhanced inhibition of α amylase and angiotensin converting enzyme
Journal of Functional Foods, 2017Co-Authors: Haripriya Shanmugam, G K Jayaprakasha, Pratibha Acharya, Bhimanagouda S PatilAbstract:Abstract To overcome the solubility and bioavailability challenges of Nomilin, we have formulated and characterized a nanoparticle-based delivery system. Nomilin nanoparticles were prepared with poly (lactic-co-glycolic acid) (PLGA) resomers of different co-polymer composition and molecular weights with two surfactant, didodecyl dimethyl ammonium bromide (DMAB) and pluronic F-68 (PF-68) at three Nomilin loading levels (30%, 40% and 50%) through modified emulsion diffusion evaporation technique. The smallest mean particle sizes, 135–188 nm, were obtained with DMAB as the surfactant. The PLGA (50:50) polymer exhibited a slow release pattern in all loading levels, except 40% loading with PF-68. Significantly higher in vitro inhibition of α-amylase and angiotensin-converting enzyme activity was observed with Nomilin-loaded PLGA nanoparticles as compared to pure Nomilin. Thus, Nomilin nanoparticles can be explored for understanding the various biological properties using in vivo studies.
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citrus Nomilin down regulates tnf α induced proliferation of aortic smooth muscle cells via apoptosis and inhibition of iκb
European Journal of Pharmacology, 2017Co-Authors: Jinhee Kim, G K Jayaprakasha, Sanjukta Chakraborty, Mariappan Muthuchamy, Bhimanagouda S PatilAbstract:Nomilin is a bitter compound present in citrus and has been demonstrated as useful for various disease preventions through anti-proliferative, anti-inflammatory, and pro-apoptotic activities. Although in vitro disease models have shown that certain limonoids in the p38 mitogen-activated protein kinase signal cascade, the downstream signaling pathways remain unclear. In this study, the effects of Nomilin on the proliferation and apoptotic pathways of human aortic smooth muscle cells (HASMCs) that forms the basis of progression of atherosclerotic diseases and restenosis was tested for the first time. The cellular uptake level and stability of Nomilin were determined by high-performance liquid chromatography and high-resolution mass spectra. Pretreatment of HASMCs with Nomilin stimulated extrinsic caspase-8, intrinsic caspase-9, and apoptotic caspase-3 and resulted in significant inhibition of TNF-α-induced proliferation. Additionally, results showed a decreased ratio of anti-apoptotic Bcl-2 protein to pro-apoptotic Bax (Bcl2/Bax), indicating mitochondrial dysfunction consistent with apoptosis. Furthermore, Nomilin significantly decreased the phosphorylation of IκBα, an inhibitor of NF-κB and subsequently, reduced the downstream inflammatory signaling in TNF-α treated HASMCs. Our findings indicate that the anti-proliferative activity of Nomilin on TNF-α-induced HASMCs results from apoptosis through a mitochondrial-dependent pathway and suppression of inflammatory signaling mediated through NF-κB.
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Production System and Storage Temperature Influence Grapefruit Vitamin C, Limonoids, and Carotenoids
2012Co-Authors: Kranthi K. Chebrolu, G K Jayaprakasha, J. Jifon, Bhimanagouda S PatilAbstract:Concentrations of grapefruit (cv. ‘Rio Red’; Citrus paradisi Macf.) bioactives grown under organic and conventional production systems were evaluated after storage at various temperatures. The first experiment was conducted in November 2008 and the second experiment was conducted in February 2011 using commercial production, processing, and packing procedures. The harvested grapefruits were stored at 23 °C (room temperature) or 9 °C for 4 weeks and analyzed for vitamin C, limonoids, and carotenoids at the end of each week using HPLC. Vitamin C levels were higher in organically grown grapefruits (41.8 mg/100 g) compared to conventionally grown grapefruits (39.2 mg/100 g) at 0 days after harvest in the first experiment. However, production system did not significantly affect vitamin C levels in the second experiment. During storage at room temperature, vitamin C degradation losses ranged from 0.5 to 7% for organically produced grapefruits and from 3 to 18% for conventional grapefruits in both experiments. In the first experiment at harvest, organically produced grapefruits had 77% higher (p ≤ 0.05) Nomilin than conventionally produced grapefruits, whereas grapefruits grown under the conventional production system had 2-fold higher lycopene levels compared to organic grapefruits. In the second experiment, both β-carotene and lycopene levels were significantly (p ≤ 0.05) higher in conventionally produced grapefruits than in organic grapefruits. Overall, conventional production significantly increased grapefruit carotenoid levels in both experiments. In general, storage temperature (room temperature and 9 °C) had minimal effects on vitamin C degradation but significant effects on the degradation of carotenoids in the first experiment
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simultaneous determination of citrus limonoid aglycones and glucosides by high performance liquid chromatography
Analytica Chimica Acta, 2007Co-Authors: Amit Vikram, G K Jayaprakasha, Bhimanagouda S PatilAbstract:High performance liquid chromatography (HPLC) method has been developed for simultaneous quantification of limonoid aglycones and glucosides on a reversed phase C18 column using a binary solvent system, coupled with diode array detector. Seven limonoids such as limonin, Nomilin, isolimonic acid, ichangin, isoobacunoic acid, limonin 17-beta-D glucopyranoside and deacetyl Nomilinic acid 17-beta-D glucopyranoside were separated and detected at 210 nm. Furthermore, limonoids were separated, identified and quantified in four varieties of citrus fruits and seeds using developed method. Limonin and limonin glucoside were found to be the predominant limonoid aglycone and glucoside, respectively, in all tested samples. The sensitivity of the method was found to be 0.25-0.50 microg for tested limonoids.
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Isolation and purification of closely related Citrus limonoid glucosides by flash chromatography
Phytochemical Analysis, 2005Co-Authors: Girija Raman, Jennifer S Brodbelt, Bhimanagouda S PatilAbstract:Several citrus limonoid glycosides have proved to be particularly difficult to purify using conventional techniques. A reversed-phase flash chromatographic technique has been developed for the separation and isolation of the closely related limonoid glucosides, Nomilin 17-β-d-glucopyranoside and Nomilinic acid 17-β-d-glucopyranoside, with confirmation of their identities by electrospray ionisation mass spectrometry. Furthermore, the semipurification of the mixture of glucosides enriched with flavanone glucosides such as naringin, narirutin and other limonoid glucosides was obtained. The closely eluting glucosides were successfully separated to achieve a good yield and purity of 93%. Copyright © 2005 John Wiley & Sons, Ltd.
Ryuichiro Sato - One of the best experts on this subject based on the ideXlab platform.
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identification of key amino acid residues in the htgr5 Nomilin interaction and construction of its binding model
PLOS ONE, 2017Co-Authors: Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro SatoAbstract:TGR5, a member of the G protein-coupled receptor (GPCR) family, is activated by bile acids. Because TGR5 promotes energy expenditure and improves glucose homeostasis, it is recognized as a key target in treating metabolic diseases. We previously showed that Nomilin, a citrus limonoid, activates TGR5 and confers anti-obesity and anti-hyperglycemic effects in mice. Information on the TGR5-Nomilin interaction regarding molecular structure, however, has not been reported. In the present study, we found that human TGR5 (hTGR5) shows higher Nomilin responsiveness than does mouse TGR5 (mTGR5). Using mouse-human chimeric TGR5, we also found that three amino acid residues (Q77ECL1, R80ECL1, and Y893.29) are important in the hTGR5-Nomilin interaction. Based on these results, an hTGR5-Nomilin binding model was constructed using in silico docking simulation, demonstrating that four hydrophilic hydrogen-bonding interactions occur between Nomilin and hTGR5. The binding mode of hTGR5-Nomilin is vastly different from those of other TGR5 agonists previously reported, suggesting that TGR5 forms various binding patterns depending on the type of agonist. Our study promotes a better understanding of the structure of TGR5, and it may be useful in developing and screening new TGR5 agonists.
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Identification of key amino acid residues in the hTGR5–Nomilin interaction and construction of its binding model
2017Co-Authors: Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro SatoAbstract:TGR5, a member of the G protein-coupled receptor (GPCR) family, is activated by bile acids. Because TGR5 promotes energy expenditure and improves glucose homeostasis, it is recognized as a key target in treating metabolic diseases. We previously showed that Nomilin, a citrus limonoid, activates TGR5 and confers anti-obesity and anti-hyperglycemic effects in mice. Information on the TGR5–Nomilin interaction regarding molecular structure, however, has not been reported. In the present study, we found that human TGR5 (hTGR5) shows higher Nomilin responsiveness than does mouse TGR5 (mTGR5). Using mouse–human chimeric TGR5, we also found that three amino acid residues (Q77ECL1, R80ECL1, and Y893.29) are important in the hTGR5–Nomilin interaction. Based on these results, an hTGR5–Nomilin binding model was constructed using in silico docking simulation, demonstrating that four hydrophilic hydrogen-bonding interactions occur between Nomilin and hTGR5. The binding mode of hTGR5–Nomilin is vastly different from those of other TGR5 agonists previously reported, suggesting that TGR5 forms various binding patterns depending on the type of agonist. Our study promotes a better understanding of the structure of TGR5, and it may be useful in developing and screening new TGR5 agonists.
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Differences in the affinity between hTGR5 and mTGR5 for Nomilin as determined using three amino acid residues.
2017Co-Authors: Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro SatoAbstract:(A) Transient transfection assays using HEK293 cells with a CRE-luciferase reporter plasmid and an expression vector for TGR5 with the indicated mutation of three unconserved residues (n = 3). (B) Each WT and mutant TGR5 was transfected into HEK293 cells together with the CRE-luciferase plasmid, and dose-response curves to Nomilin (left panel) and TLCA (right panel) were examined. The lower panel shows the EC50 values of each TGR5 for Nomilin and TLCA (n = 3). Significant differences between the Nomilin responses were analyzed using one-way ANOVA (Tukey’s post hoc test); **p < 0.01 and *p < 0.05 for hTGR5-WT; ##p < 0.01 and #p < 0.05 for mTGR5-WT. The values represent the mean ± SD.
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Response profiles of multiple mouse-to-human point mutations in Nomilin and TLCA.
2017Co-Authors: Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro SatoAbstract:Transient transfection assays using HEK293 cells with a CRE-luciferase reporter plasmid and expression vector for TGR5 with indicated point mutation of nine unconserved residues in ECL2 (A) and TM3 (B). After transfection for 24 h, the cells were treated with TLCA and Nomilin (100 μM each) for another 5 h. Then, luciferase reporter activities were quantified (n = 3). Significant differences between the Nomilin responses were analyzed using one-way ANOVA (Tukey’s post hoc test); **p < 0.01 for mTGR5-WT. The values represent the mean ± SD.
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Binding modes and docking interactions of Nomilin with hTGR5.
2017Co-Authors: Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro SatoAbstract:(A and B) Hydrophilic hydrogen-bonding interaction between Nomilin and three amino acid residues of hTGR5 are shown with red dashes.
Shin Hasegawa - One of the best experts on this subject based on the ideXlab platform.
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Nomilin acetyl lyase a bacterial enzyme for Nomilin debittering of citrus juices
Journal of Food Science, 2006Co-Authors: Zareb Herman, Shin Hasegawa, O U PeterAbstract:Nomilin acetyl-lyase, an enzyme responsible for the conversion of bitter Nomilin to nonbitter obacunone was purified from cell-free extracts of Corynebacterium fuscians by (NH4)2SO4 precipitation, followed by HPLC gel filtration and ion exchange chromatography. The electrophoretically pure preparation represented a 1050-fold increase in specific activity with a recovery of 38%. The enzyme, (MW 90,000) required sulfhydryl groups for its catalysis, had a pH optimum of 8.5, a Km of 38.1 PM, and a Vmax of 4.83 μmoles/min. Obacunone A-ring lactone hydrolase, which catalyzes the conversion of obacunone to obacunoate, was also purified from the extract by HPLC gel filtration.
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Limonoid Glucosides in Citrus Seeds
Agricultural and biological chemistry, 2006Co-Authors: Yoshihiko Ozaki, Zareb Herman, Chi H. Fong, Hisao Maeda, Masaki Miyake, Yasushi Ifuku, Shin HasegawaAbstract:The amounts of limonoid glucosides were measured in the seeds of grapefruit (Citrus paradisi), lemon (C. limon), Valencia orange (C. sinensis), tangerine (C. reticulata), Fukuhara (C. sinensis Osbeck Hort.), Hyuganatsu (C. tamurana Hort. ex Tanaka), Shimamikan (C. kinokuni Hort. ex Tanaka) and Sanbokan (C. sulcata Hort. ex Takahashi). All the seeds contained 17-β-d-glucopyranosides of limonin, Nomilin, obacunone, deacetylNomilin, Nomilinic acid and deacetylNomilinic acid. The total limonoid glucoside content ranged from 0.31 to 0.87% of the dry weight. The concentration of Nomilin glucoside was highest among the glucosides found in the seeds. All the seeds also contained the major neutral limonoid aglycones commonly found in citrus, namely limonin, Nomilin, deacetylNomilin, obacunone and ichangin. As previously reported, limonin was the predominant aglycone.
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limonoids in seeds of iyo tangor citrus iyo hort ex tanaka
Food Science and Technology Research, 2003Co-Authors: Toshinao Ishii, Hideaki Ohta, Yoichi Nogata, Masamichi Yano, Shin HasegawaAbstract:Iyo tangor (Citrus iyo hort. ex Tanaka) seeds contained limonin, Nomilin, obacunone and deacetylNomilin, in order of decreasing concentration. They also contained the 17-β-D-glucopyranosides of Nomilin, obacunone, limonin, deacetyNomilin and Nomilinic acid. Total limonoid aglycone concentration in the seeds was 873 mg per 100 g on a dry weight basis and total limonoid glucoside concentration was 446 mg. The composition and relative concentration of each limonoid aglycone and glucoside in Iyo tangor seeds were very similar to those of other citrus species distributed widely in western Japan such as Valencia orange (C. sinensis Osbeck), Sanbokan (C. sulcata hort. ex Tanaka) and Hyuganatsu (C. tamurana hort. ex Tanaka). These data reveal that Iyo tangor taxonomically belongs to the same group as those citrus species.
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modification of limonoid metabolism in suspension cell culture of citrus
Plant Biotechnology, 2002Co-Authors: Tomoko Endo, Shin Hasegawa, Masayuki Kita, Takehiko Shimada, Takaya Moriguchi, Tetsushi Hidaka, Ryoji Matsumoto, Mitsuo OmuraAbstract:For the metabolic engineering of bio-functional substances in Citrus, metabolic changes of limonoids were investigated in embryogenic cell cultures of Citrus and Fortunella. When embryogenic cells of Citrus and Fortunella were cultured for four weeks in the liquid subculture medium containing Nomilin, most species converted Nomilin to obacunone and limonin. In addition, calamin group limonoids were produced in Fortunella and Calamondin cells. DeacetylNomilin was produced from Nomilin in the cells of C. ichangensis and its related species. Exogenously added limonin into medium was not metabolized. The embryoid formation in C.aurantium did not affect the limonoid metabolism. All cells cultured without the presence of Nomilin or limonin did not generate any limonoids. Furthermore, transgenic C. sinensis cell harboring a chimeric limonoid UDP-glucosyltransferase (limonoid GTase) gene was generated. The conversion of limonin into limonin 17-β-D-glucopyranoside (LG) demonstrated an efficient assay system for the transgene.
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Limonoids in pummelos [Citrus grandis (L.) Osbeck]
Journal of Food Science, 1995Co-Authors: Hideaki Ohta, Shin HasegawaAbstract:Juice and seeds from 16 cultivars of mature pummelo fruits were analyzed for limonoid content. Pummelo juice contained an average of 18 ppm limonin and 29 ppm total limonoid glucosides. Compared to other juices, ptmnnelo contained very high concentrations of limonin and very low concentrations of limonoid glucosides. Limonin, Nomilin, obacunone and trace amounts of deacetyhromilin were found in pummelo seeds. The 17–β-D-glucopyranoside derivatives (glucosides) of Nomilin, Nomilinic acid and obacunone were also present. Total limonoid aglycone concentration in the seeds ranged from 773 ppm to 9,900 ppm and total limonoid glucosides ranged from 130 ppm to 1,912 ppm.
Xiaolin Ding - One of the best experts on this subject based on the ideXlab platform.
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screening for limonoid glucosides in citrus tangerina tanaka tseng by high performance liquid chromatography electrospray ionization mass spectrometry
Journal of Chromatography A, 2000Co-Authors: Qingguo Tian, Xiaolin DingAbstract:A screening method for limonoid glucosides in the peel of Citrus tangerina (Tanaka) Tseng, which utilizes high-performance liquid chromatography (HPLC) with diode-array detection and interfaced to electrospray ionization mass spectrometry, has been developed. In this way, the UV-Vis spectra and the mass spectra indicate the presence of limonoid glucosides without the necessity of isolating the individual compounds. Two major limonoid glucosides--obacunone glucoside (OG) and Nomilin glucoside (NG)--were identified in the methanol extract of the peel. The two limonoid glucosides were taken as the target and isolated by means of preparative HPLC on a C18 reversed-phase column with an acidic acetonitrile-water mobile phase. The structures of OG and NG were further confirmed by nuclear magnetic resonance spectrometry.
Amadeo R Fernandezalba - One of the best experts on this subject based on the ideXlab platform.
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matrix effects and interferences of different citrus fruit coextractives in pesticide residue analysis using ultrahigh performance liquid chromatography high resolution mass spectrometry
Journal of Agricultural and Food Chemistry, 2017Co-Authors: Natalia Besil, Veronica Cesio, Horacio Heinzen, Amadeo R FernandezalbaAbstract:The matrix effects of ethyl acetate extracts from seven different citrus fruits on the determination of 80 pesticide residues using liquid chromatography coupled to high-resolution time-of-flight mass spectrometry (UHPLC-(ESI)-HR-TOF) at 4 GHz resolution mode were studied. Only 20% of the evaluated pesticides showed noticeable matrix effects (ME) due to coelution with natural products between tR = 3 and 11 min. Principal component analysis (PCA) of the detected coextractives grouped the mandarins and the orange varieties, but separated lemon, oranges, and mandarins from each other. Matrix effects were different among species but similar between varieties, forcing the determination of pesticide residues through matrix-matched calibration curves with the same fruit. Twenty-three natural products (synephrine, naringin, poncirin, glycosides of hesperitin, limonin, Nomilin, and a few fatty acids, among others) were identified in the analyzed extracts. Twelve of the identified compounds coeluted with 28 of the ...