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At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the antioxidant capacity of limonin, nomilin, and limonin glucoside.

The antioxidant capacity (AOC) of three representative citrus limonoids, limonin, nomilin, and limonin glucoside, was examined by the oxygen radical absorbance capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), beta-carotene-linoleic acid bleaching, and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assays. Pure compounds and proper negative (cinnamic acid) and positive (2,6-di-tert-butyl-4-methylphenol (BHT) and ascorbic acid) controls were used to remove any ambiguity in interpreting results. In all cases, limonin and nomilin gave results equivalent to those of cinnamic acid, indicating that they do not possess any inherent AOC and should not be considered antioxidants. Similar results were observed for limonin glucoside, with the exception of an anomalous result obtained from the beta-carotene-linoleic acid bleaching assay. Limonin glucoside was deemed not to be an antioxidant on the basis of the three unequivocal assays.

Antioxidants↗
PubMed2001

Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin.

The modifying effects of dietary administration of the citrus limonoids obacunone and limonin on azoxymethane (AOM)-induced colon tumorigenesis were investigated in two experiments in male F344 rats. In a pilot study, we examined the modifying effects of obacunone and limonin on AOM-induced (20 mg/kg body wt, once a week for 2 weeks) formation of aberrant crypt foci (ACF). Dietary feeding of both compounds at dose levels of 200 and 500 p.p.m. during AOM exposure for 4 weeks ('initiation' feeding) or after AOM treatment for 4 weeks ('post-initiation' feeding) significantly inhibited ACF formation (55-65% reduction by 'initiation' feeding, P < 0.001; 28-42% reduction by 'post-initiation' feeding, P < 0.05-0.002). In a long-term study designed to confirm the protective effects of obacunone and limonin on ACF development, one group was treated with AOM alone and another four groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 3 weeks (initiation phase) or 29 weeks (post-initiation phase). Two groups were treated with obacunone or limonin alone (500 p.p.m. in diet) and one group was maintained on the basal diet. At the termination of the study, dietary exposure to obacunone or limonin during the initiation phase was found to have significantly reduced the incidence of colonic adenocarcinoma (72 versus 25 or 6%, P = 0.004 or 0.00003). Obacunone or limonin feeding during the post-initiation phase also reduced the frequency of colonic adenocarcinoma (72 versus 13%, P = 0.0002). Our results suggest that the citrus limonoids obacunone and limonin might be useful for the prevention of human colon cancers.

Animals↗
PubMed2000

Calorimetric evidence of differentiated transport of limonin and nomilin through biomembranes.

The effect exerted by two structurally similar limonoids possessing antifeedant and anticancer activity, limonin and nomilin, on the thermotropic behavior of model membranes constituted by dimyristoylphosphatidylcholine (DMPC) vesicles was studied by differential scanning calorimetry. Attention was directed to evaluate modifications in phytochemical-lipid interaction induced by compound structure and lipophilicity and to evidence their different membrane penetration. The two examined compounds, when dispersed in liposomes during their preparation, were found to exert a very different action on the L(beta)-L(alpha) gel-to-liquid crystal phase transition of DMPC multilamellar vesicles. Nomilin caused a detectable effect on the transition temperature (T(m)), shifting it toward lower values with a concomitant small decrease of the associated enthalpy (DeltaH) changes, while limonin was not able to modify the lipid vesicles thermotropic behavior. Modifications induced by nomilin were a function of phytochemical concentration, while the different behavior of limonin can be due to the different polarity induced by the presence of the single A ring in nomilin that possesses an acetyl group versus the A,A' ring system of limonin. Solid limonoids and aqueous dispersions of multilamellar (MLVs) or unilamellar vesicles (LUVs) (limonoids molar fraction 0. 045, 0.12, and 0.18) were left in touch for long incubation times at temperatures higher than T(m) to detect their spontaneous transfer through the medium. By following this procedure, no interaction was detected for limonin with lipid vesicles. The rate of transfer and interaction of nomilin was a function of the kind of vesicle species (faster for LUV, slower for MLV). The interaction, monitored by compound transfer from the solid phytochemical to the lipidic species after several periods of incubation, was on the same order as that detected by preparation carried out in organic solvent. The obtained results can be explained in terms of compound hydrophobicity, and a relation between compound structure and membrane interaction can be suggested. This allows the membrane interaction with nomilin, but the low water solubility of limonin hinders or totally blocks its transfer through the aqueous medium.

Benzopyrans↗
PubMed2003

Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells.

In the last years several plant-derived natural compounds have been screened for their anti-HIV activity in order to find lead compounds with novel structures or mechanisms of action. Among these, several triterpenoids have been found to exhibit an antiretroviral activity with different mechanisms of action. In this study the effect of two limonoids, limonin and nomilin, on the growth of human immunodeficiency virus-1 (HIV-1) in culture of human peripheral blood mononuclear cells (PBMC) and on monocytes/macrophages (M/M) is described. Limonin and nomilin were found to inhibit the HIV-1 replication in all cellular systems used. A dose-dependent inhibition of viral replication was observed in PBMC isolated from healthy donors and infected with HIV-1 strain after incubation with limonin and nomilin (EC (50) values: 60.0 microM and 52.2 microM, respectively). The two terpenoids inhibited at all concentrations studied the production of HIV-p24 antigen even when the PBMC employed were chronically infected (EC (50) values of 61.0 microM for limonin and 76.2 microM for nomilin). Moreover, these compounds inhibited the HIV-1 replication even in infected M/M. In this cellular system the inhibitory effect was significant at the concentrations of 20 microM, 40 microM and 80 microM starting from day 14 and reached the maximum effect after 18 days of incubation. As regards the mechanism of action, limonin and nomilin inhibit in vitro HIV-1 protease activity. In general, the results obtained point out a similar anti-HIV activity of limonin and nomilin indicating that this activity is not drastically influenced by the structural difference between the two compounds.

Anti-HIV Agents↗
PubMed1998

Antinociceptive and anti-inflammatory activities of limonin isolated from the fruits of Evodia rutaecarpa var. bodinieri.

Antinociceptive and anti-inflammatory effects of limonin isolated from the dried fruits of Evodia rutaecarpa var. bodinieri were investigated. Oral administration of 30 or 100 mg/kg limonin significantly decreased the frequency of licking and biting behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. Limonin inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin. Limonin also showed inhibitory effects on bradykinin-induced paw edema and arachidonic acid-induced ear swelling. These results suggest that limonin possesses an antinociceptive effect and the effect may be accompanied by an anti-inflammatory action, and that the antinociceptive activity in Evodiae Fructus is partially attributable to limonin.

Analgesics↗
PubMed2005

Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract.

Evodia fruit (Evodiae Fructus) is used as a herbal medicine prepared from the matured fruit of the Evodia rutaecarpa Bentham or Evodia officinalis Dode, of the Rutaceae plant family. An extract of Evodia fruit in the presence of NADPH was shown to inhibit human liver microsomal erythromycin N-demethylation activity, mediated by cytochrome P450 3A4 (CYP3A4), in a preincubation-time dependent manner. The present study was conducted to identify components of Evodia fruit extract having preincubation-time dependent inhibitory effects on CYP3A4 by analyzing human liver microsomal erythromycin N-demethylation activity. Rutaecarpine, a major component of Evodia fruit, and limonin caused the most dramatic decrease in residual CYP3A4 activity (IC50 before and after 20 min preincubation with: rutaecarpine, >100 microM and 1.4 microM; limonin, 23.5 microM and 1.8 microM, respectively). Furthermore, rutaecarpine and limonin were identified as mechanism-based inhibitors of CYP3A4 from the following observations: 1) The inhibitory effects of rutaecarpine and limonin on CYP3A4 activity were dependent on the preincubation time, 2) The inhibition required NADPH, 3) The inhibition was depressed in the presence of the competitive CYP3A4 inhibitor, ketoconazole, 4) Dialysis resulted in no recovery of CYP3A4 activity. The kinetic parameters for inactivation k(inact) and K(I) were: 0.387 min-1 and 107.7 microM for rutaecarpine, 0.266 min-1 and 23.2 microM for limonin, respectively. These results indicate that rutaecarpine and limonin are mechanism-based inhibitors of CYP3A4.

Alkaloids↗
PubMed2000

Citrus limonoids obacunone and limonin inhibit azoxymethane-induced colon carcinogenesis in rats.

Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on the development of aberrant crypt foci (ACF), the activity of detoxification enzymes, glutathione S-transferase (GST) and quinone reductase (QR), and cell proliferation activity were investigated in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were administered in the diet, during the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM-induced tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused significant reduction (55-65% by "initiation" feeding and 28-42% by "postinitiation" feeding) in the yield of ACF. The ability to reduce the proliferating cell nuclear antigen-labeling index in crypts and correlated well with the prevention of ACF. In a subsequent long-term experiment (38 weeks), in which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin during the initiation or post-initiation phase, both compounds in diet caused significant reduction (65%-92% inhibition) in the incidence of colonic adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess chemopreventive effects on chemically induced rat colon carcinogenesis.

Animals↗
PubMed2004

Characterization of limonin glucoside metabolites from human prostate cell culture medium using high-performance liquid chromatography/electrospray ionization mass spectrometry and tandem mass spectrometry.

The metabolism of limonin 17-beta-D-glucopyranoside (LG) by non-cancerous (RWPE-1) and cancerous (PC-3) human prostate epithelial cells was investigated using high-performance liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) with in-source fragmentation and tandem mass spectrometry (MS/MS). During positive ion LC/ESI-MS, LG formed an abundant sodiated species ([M+Na]+) while the protonated molecule was barely observable. [M+Na]+ further fragmented into the less abundant [LARL+H]+ and a predominantly protonated aglycone molecule (limonin) due to in-source fragmentation. The major metabolite, limonin A-ring lactone (LARL), formed an abundant protonated molecule that was fragmented into a protonated molecule of limonin by loss of one molecule of water. In MS/MS by collisionally activated dissociation (CAD), LG produced the sodiated aglycone, [aglycone+Na]+, while LARL fragmented into [M+H]+ of limonin and fragment ions resulted by further loss of water, carbon monoxide and carbon dioxide, indicating the presence of oxygenated-ring structures. The limits of detection of LG were 0.4 and 20 fmol in selected-ion monitoring (SIM) and selected-reaction monitoring (SRM) detection, respectively.

Cell Line, Tumor↗
PubMed1989

Determination of limonin in grapefruit juice and other citrus juices by high-performance liquid chromatography.

A method has been developed for the quantitation of the bitter component limonin in grapefruit juice and other citrus juices. The sample clean-up consisted of centrifugation, filtration and a selective, rapid and reproducible purification with a C2 solid-phase extraction column. The limonin concentration was determined by high-performance liquid chromatography on a C18 column with UV detection at 210 nm. A linear response was obtained from 0.0 to 45 ppm limonin. The minimum detectable amount was 2 ng. The minimum concentration which was detected without concentration with good precision was 0.1 ppm. The method was also used for the determination of limonin in different types of oranges, including navel oranges, mandarins, lemons, limes, pomelos and uglis.

Beverages↗
PubMed1992

Inhibition of hamster buccal pouch carcinogenesis by limonin 17-beta-D-glucopyranoside.

Limonin 17-beta-D-glucopyranoside, nomilin 17-beta-D-glucopyranoside, and nomilinic acid 17-beta-D-glucopyranoside, three limonoid glucosides isolated from oranges, were tested for cancer chemopreventive activity. Eighty female Syrian hamsters were divided into four equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside (Group III), or nomilinic acid 17-beta-D-glucopyranoside (Group IV). After this initial treatment, the left buccal pouches of 16 hamsters from each group were painted five times per week. Two or three times per week the pouches were treated with a 0.5% solution of the carcinogen 7,12-di-methylbenz[a]anthracene (DMBA) dissolved in mineral oil. On alternate days, the pouches were treated with water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside, or nomilinic acid 17-beta-D-glucopyranoside. The 16 remaining animals were used as controls. These hamsters were treated five times per week, one day with mineral oil and the next with either water (Group I) or one of the 3.5% solutions of the limonoid glucosides (Groups II-IV). After 15 weeks (71 applications), the hamsters were killed. Multiple tumors were common in the animals treated with DMBA; however, the animals treated with limonin 17-beta-D-glucopyranoside exhibited a 55% decrease in average tumor burden. Further comparisons between Groups I and II showed that this reduction in tumor burden was mainly due to a decrease in tumor mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Competitive solid phase enzyme-linked immunoassay for the quantification of limonin in citrus.

A solid-phase enzyme immunoassay for the quantitative determination of the bitter triterpene-lactone, limonin, in citrus juice samples is described. As little as 0.1 ppm of limonin can be detected. Quantitative results are available within 1 h of total assay time. The assay makes use of a limonin-alkaline phosphatase tracer of high immunoreactivity and has been semiautomated using antibody-coated polystyrene microcuvettes, a vertical light path photometer, and a forced-air microplate incubator.

Alkaline Phosphatase↗
PubMed2004

Determination of limonin D-ring lactone hydrolase activity by solid phase extraction with indirect fluorescence detection.

A method for the evaluation of limonin D-ring lactone hydrolase activity is described. The method utilizes solid phase extraction (SPE) for the isolation of limonin A-ring limonoate (LARL), which is subsequently converted to limonin and quantitated by fluorescence. The fluorescence method is capable of quantifying the formation of LARL in concentrations as low as 75 ng and is applicable to both purified and crude enzyme preparations. The coupling of SPE with fluorescence detection allows for the simple and rapid analysis of samples.

Citrus↗
PubMed2006

Evidence of indigenous NAH plasmid of naphthalene degrading Pseudomonas putida PpG7 strain implicated in limonin degradation.

A well characterized naphthalene-degrading strain, Pseudomonas putida PpG7 was observed to utilize limonin, a highly-oxygenated triterpenoid compound as a sole source of carbon and energy. Limonin concentrations evidenced a 64% reduction over 48 h of growth in batch cultures. Attempts were made to acquire a plasmid-less derivative via various methods (viz. Ethidium Bromide, SDS, elevated temperature & mitomycin C), among which the method involving mitomycin C (20 ug/ml) proved successful. Concomitant with the loss of plasmid in P. putida PpG7 strain, the cured derivative was identified as a lim- phenotype. The lim+ phenotype could be conjugally transferred to the cured derivative. Based on the results of curing with mitomycin C, conjugation studies and presence of ndo gene encoding naphthalene 1,2 dioxygenase, it was demonstrated that genes for the limonin utilization were encoded on an 83 kb indigenous transmissible Inc. P9 NAH plasmid in Pseudomonas putida PpG7 strain.

DNA, Bacterial↗
PubMedDate not supplied

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.

Administration, Oral↗
PubMed1988

Quantitative determination of limonin in citrus juices by HPLC using computerized solvent optimization.

The commercially available computer program, Drylab, for optimization of separations by high-performance liquid chromatography (HPLC) using binary solvent mixtures is used to improve an HPLC method for separation of the bitter principle, limonin, in grapefruit and navel orange juices. Best conditions for separation of limonin in a reasonable time are 30 to 32% acetonitrile in water at 0.9 mL/min using a 5-micron C18 column 10 cm long. These conditions are used to analyze grapefruit and navel orange juice samples, and these HPLC results are compared with values determined by enzyme immunoassay or thin-layer chromatography (TLC) on the same samples.

Beverages↗
PubMed2005

Determination of limonin in rat plasma by liquid chromatography-electrospray mass spectrometry.

A simple, sensitive and selective liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI/MS) method for determination of limonin (LM) in rat plasma has been developed and validated. The method had advantages of a single liquid-liquid extraction with ether and high sensitivity. Analyses were conducted at a flow rate of 0.2 ml/min by a gradient elution. The detection utilized selected ion monitoring in the negative ion mode at m/z 460.00 and 423.15 for the deprotonated molecular ions of LM and the internal standard, respectively. The quantitation limit for LM in rat plasma was 1.0 ng/ml. The linearity was also excellent over the concentration range of 1.9-500 ng/ml of LM. The intra- and inter-day precision (relative standard deviation (R.S.D.%)) was lower than 10% and accuracy ranged from 90 to 110%, showing a good reproducibility. This developed method was successfully applied to analysis of LM in biological fluids.

Animals↗
PubMed2001

Extraction parameters and capillary electrophoresis analysis of limonin glucoside and phlorin in citrus byproducts.

Limonin glucoside (LG) and phlorin were extracted from citrus fruit tissues and assayed by capillary electrophoresis (CE). LG was determined in dried [1.20 +/- 0.10 mg of dry weight (dw)] and wet peel residues (1.16 +/- 0.04 mg of dw), orange juice finisher pulp (0.58 +/- 0.03 mg of dw), dried grapefruit seeds (2.70 +/- 0.15 mg of dw), and 50 degrees Brix molasses (2225 +/- 68 mg/L). Phlorin was purified from orange peel residue and grapefruit albedo, and concentrations were determined in some citrus products. Phlorin and LG were extracted from residues with water/pectinase or with water solutions of methanol and ethanol. Efficient LG extraction from grapefruit seeds (2.40 +/- 0.15 mg/g) was achieved with 50-65% methanol, solvent polarity P' approximately equal to 7-8. Extracts were purified and concentrated by adsorptive resins and HPLC to obtain 95% pure compounds of LG and phlorin. CE analysis did not require extract purification beyond filtration. LG and phlorin migrated as anions in electropherograms containing peaks representing other citrus flavonoids and limonoid glucosides.

Citrus↗