Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Safrole”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1975

[Effect of anisole, anethole, butylhydroxyanisole and safrole on intestinal absorption in the rat (author's transl)].

Using an in situ method of perfusion for rat intestine, we have studied the effect of anisole, anethole, butylhydroxyanisole (BHA) and safrole on the absorption of three metabolites: glucose, butyric acid and methionine. At a concentration of 2 mg/ml of perfusion medium, safrole, and particularly BHA, reduce the absorption of glucose and methionine but have no effect on that of butyric acid. These results could be explained by variations in intestinal water absorption induced by methoxybenzene compounds, or by changes in the digestive mucosa seen in histological studies.

Alkenes↗
PubMed1986

Differences in the covalent binding of benzo[a]pyrene, safrole, 1'-hydroxysafrole, and 4-aminobiphenyl to DNA of pregnant and non-pregnant mice.

The effects of pregnancy on the covalent binding of several carcinogens to DNA were investigated in mice. Non-pregnant or timed-pregnant (18th day of gestation) ICR mice of similar age were treated with benzo[a]pyrene (BP, 200 mumol/kg), safrole (600 mumol/kg), 1'-hydroxysafrole (400 mumol/kg), 4-aminobiphenyl (4-ABP, 800 mumol/kg), or trioctanoin (4 ml/kg) per os. Tissue DNA adduct levels at 24 h after carcinogen treatment were analyzed via a 32P-postlabeling assay. Pregnancy lowered the binding of the ultimate carcinogenic metabolite of BP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE I), to liver and lung DNA by 29-41%, but not the binding of other metabolites. The binding of safrole and its proximate carcinogen, 1'-hydroxysafrole, to liver and kidney DNA was increased 2.3-3.5 fold. Pregnancy decreased the binding of 4-ABP to liver DNA by approximately 18% but increased its binding to kidney DNA by 67%. The results suggest that exposure to some genotoxic compounds, especially those requiring conjugation reactions for metabolic activation, may be more hazardous during pregnancy than in the non-pregnant state.

Aminobiphenyl Compounds↗
PubMed2005

Upregulating of Fas, integrin beta4 and P53 and depressing of PC-PLC activity and ROS level in VEC apoptosis by safrole oxide.

Previously, we found that safrole oxide could trigger vascular endothelial cell (VEC) apoptosis. In this study, to investigate its mechanism to induce apoptosis in VECs, the activities of nitric oxide synthetase and phosphatidylcholine specific phospholipase C, the level of reactive oxygen species and the expressions of Fas, integrin beta4 and P53 were analyzed. The data showed that safrole oxide induced apoptosis by increasing the expressions of Fas, integrin beta4 and P53, and depressing the activity of Ca(2+)-independent phosphatidylcholine-specific phospholipase C and intracellular reactive oxygen species levels in VECs.

Apoptosis↗
PubMed1985

Interactions of safrole and isosafrole and their metabolites with cytochromes P-450.

The structural features which determine interaction of safrole and related methylenedioxyphenyl compounds with cytochromes P-450 or P-448, and determine the induction of these two classes of the cytochrome, have been studied. All methylenedioxyphenyl compounds studied interact with both cytochromes P-450 and P-448 eliciting type I spectral changes and it has been found that the allyl 4-substituent is important in these interactions. Methylenedioxyphenyl compounds with an oxidised allyl 4-substituent exhibited higher affinity for cytochrome P-448 while those possessing an intact allyl or methylvinyl group generally showed higher affinity for cytochrome P-450. Compounds possessing intact allyl and methylenedioxyphenyl groups (safrole, isosafrole and myristicine) were the most potent inducers of cytochromes P-450 and P-448; compounds containing an intact allyl group only (estragole, allybenzene and eugenol methyl ether) or an oxidized allyl group and an intact methylenedioxyphenyl group (epoxysafrole) were inducers of P-448 only.

Animals↗
PubMed1979

Iron negative foci and nodules in safrole-exposed mouse liver made siderotic by iron-dextran injection.

A procedure for the production of mouse hepatic siderosis is described which results in extensive iron deposition in all lobular zones. Mice exposed to safrole for 24 weeks displayed basophilic and acidophilic foci which did not accumulate iron. 36 weeks of dietary safrole exposure resulted in nodular lesions comprised of basophilic and hyalinized cells. The nodules displayed decreased or negative reactions for iron in hepatic parenchymal cells when the surrounding liver was siderotic.

Animals↗
PubMed2003

Effects of novel safrole oxide derivatives, 1-methoxy-3-(3,4-methylenedioxyphenyl)-2-propanol and 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol, on apoptosis induced by deprivation of survival factors in vascular endothelial cells.

Two safrole oxide derivatives, 1-methoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (MOD) and 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (EOD), were newly synthesized as promoters of apoptosis in vascular endothelial cells (VECs). The purpose of this study was to investigate the effects of these two safrole oxide derivatives on cell growth and apoptosis induced by deprivation of survival factors (serum and fibroblast growth factors, aFGF and bFGF) in VECs. Morphological changes were observed with light microscopy. Cell growth was determined by using MTT (3-[4, 5-dimethyl thiazol-2-yl]-2, 5-diphenytetrazolium) method. DNA fragmentation was analyzed by agarose gel electrophoresis and fluorescence microscopy. Apoptosis rate and cell cycle distribution were analyzed by flow cytometry (FCM). The cells deprived of FGF and serum were exposed to MOD 10-40 mg l(-1) for 24 h. Cell growth was suppressed (P<.01), while detachment and DNA fragmentation of these cells were promoted (P<.01). When the cells were treated with MOD30 mg l(-1) for 24 h, apoptosis rate was 21.43% (P<.01). The fact that 66.50% of the cells were trapped in S phase of cell cycle indicated that the cell cycle was blocked at S phase. Treated with EOD 10-40 mg l(-1) for 24 h, the cells were observed; the results showed that VEC growth was inhibited and the apoptosis was triggered (P<.01). At 30 mg l(-1) concentration, EOD blocked 55.22% of the cells at S phase. The data suggested that MOD and EOD might promote apoptosis of VEC by blocking the cell cycle at S phase.

Apoptosis↗
PubMed1984

32P-post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. II. Newborn male B6C3F1 mice.

When a series of nine alkenylbenzenes were administered to preweanling male mice, safrole, estragole and methyleugenol induced a significant incidence of hepatic carcinomas, while eugenol, anethole, elemicin, myristicin, dill apiol and parsley apiol did not (Miller et al., Cancer Res., 43, 1124-1134, 1983). Following the protocol used to test seven of these compounds, male C57Bl X C3H/He F1 mice were injected with 0.25, 0.5, 1.0 and 3.0 mumol of a compound on days 1, 8, 15 and 22 after birth, respectively. Groups of mice were killed and their liver DNA isolated on days 23, 29 and 43, and analysed by a modified 32P-post-labelling procedure. Highest levels of adducts were detected with methyleugenol (72.7 pmol/mg DNA), estragole (30.0) and safrole (17.5). After correction for liver growth it was estimated that most of these adducts were still present at 43 days. Significant levels of DNA binding by myristicin (7.8 pmol/mg DNA) and elemicin (3.7) were also found but in the former case the adducts were less persistent. Only low levels of adducts were detected with anethole, dill apiol and parsley apiol (less than 1.4 pmol/mg DNA); no DNA binding was detected with eugenol. Thus, all but one of the alkenylbenzenes studied became bound to newborn mouse-liver DNA, but the levels and the persistence of adducts formed by the carcinogenic compounds were greater.

Allylbenzene Derivatives↗
PubMed2006

Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry.

Seeds of nutmeg are used as spice, but they are also abused because of psychotropic effects described after ingestion of large doses. It was postulated that these effects could be attributable to metabolic formation of amphetamine derivatives from the main nutmeg ingredients elemicin (EL), myristicin (MY), and safrole (SA). In a case of a suspected nutmeg abuse, neither such amphetamine derivatives nor the main nutmeg ingredients could be detected in urine. The metabolites of EL, MY, and SA were identified using gas chromatography-mass spectrometry in rat urine and their presence in human urine of the nutmeg abuser was confirmed. The identified metabolites indicated that EL, MY, and SA were once and twice hydroxylated at the side chain. In addition, EL was O-demethylated at 2 positions followed by side chain hydroxylation. MY and SA were demethylenated and subsequently methylated. In the human urine sample, the following metabolites could be identified: O-demethyl elemicin, O-demethyl dihydroxy elemicin, demethylenyl myristicin, dihydroxy myristicin, and demethylenyl safrole. As in the human urine sample, neither amphetamine derivatives nor the main nutmeg ingredients could be detected in the rat urine samples. Finally, toxicologic detection of nutmeg abuse was possible by identification of the described metabolites of the EL, MY, and SA in urine applying the authors' systematic toxicologic analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction of analytes, and microwave-assisted acetylation of extracted analytes.

Allylbenzene Derivatives↗
PubMedDate not supplied

Effects of novel safrole oxide derivatives, 1-propyl-3-(3,4-methylenedioxyphenyl)-2-propanol and 1-isopropoxy-3-(3,4-methylenedioxyphenyl)-2-propanol, on apoptosis induced by deprivation of survival factors in vascular endothelial cells.

Two safrole oxide derivatives, 1-propoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (FOD) and 1-isopropoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (GOD), were newly synthesized as promoters of apoptosis in vascular endothelial cells. The purpose of this study was to investigate the effects of these two safrole oxide derivatives on cell growth and apoptosis induced by deprivation of survival factors (serum and fibroblast growth factors, aFGF and bFGF) in vascular endothelial cells (VECs). MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) method, agarose gel electrophoresis, laser scanning confocal microscopy, flow cytometry (FCM), and immunofluorescence assay were used. The cells deprived of FGF and serum were exposed to FOD or GOD 30 to 90 mg x L(-1) for 24 h, cell growth was suppressed (p < .05), whereas detachment and DNA fragmentation of these cells were promoted (p < .01). When the cells were treated with FOD 90 mg x L(-) for 24 h, apoptosis rate was 14.99% (p < .01). There were more cells in G2-M phase and less cells in S phase. At 90 mg x L(-1) concentration, GOD blocked 77.03%of the cells at G0-G1 phase., P53 level in VEC exposed to FOD or GOD was increased (p < .01). The data suggested that FOD and GOD might promote apoptosis of VEC by affect the cell cycle distribution, whereas P53 was involved in this pathway.

Apoptosis↗
PubMed1991

[Determination of myristicin and safrol in the volatile oil of semen Myristicae and its processed products by TLC-scanning].

This paper reports the determination of myristicin and safrol in the volatile oil of Semen Myristicae and its processed products by TLC-Scanning. The results showed that in the processed products myristicin decreased markedly and safrol decreased slightly. The quantity of myristicin roasted with paste less than with wheat bran less than with talcum powder less than the unprocessed one. The toxicity of Semen Myristicae is related to the quantities of myristicin.

Allylbenzene Derivatives↗
PubMed1984

Quantitative analysis of alpha, beta-thujone, pulegone, safrole, coumarin and beta-asarone in alcoholic beverages by selected-ion monitoring.

Interest in the quantitative analysis of flavouring agents in alcoholic beverages arises from the possible toxicological consequences deriving from their use. The method reported here, based on gas chromatography with selected-ion monitoring mass spectrometry (SIM), allows the simultaneous measurement of alpha, beta-thujone, pulegone, safrole, coumarin and beta-asarone at the ppb level in alcoholic beverages.

Alcoholic Beverages↗
PubMed1992

The synthesis and anti-inflammatory properties of a new sulindac analogue synthesized from natural safrole.

The synthesis of the new sulindac (3) analogue (Z)-5,6-methylenedioxy-2-methyl-1-(p-methylsulfinylbenzylidene)-3- indenyl acetic acid (1) from natural safrole (2), an abundant natural product occurring as the principal chemical constituent of Sassafraz oil, is described. The principal feature of this route is shortness, stereoselectivity, and high overall yield. The new analogue is produced in a yield of approximately 30% from the natural product. The results include the anti-inflammatory activity of 1 as well as that for its corresponding sulfide (12), a synthetic precursor of 1 that may be an important metabolic product of 1 by analogy to 3 itself. The anti-inflammatory profiles of these derivatives, measured in the carrageenan-induced rat paw edema test, indicated a 50% effective dose of 42 mg/kg for 1 and of 23 mg/kg for 12, confirming the structure-activity relationships of these agents. These results indicate that the new analogue 1 could represent a prodrug with a similar therapeutic profile to that of the pharmaceutical product 3.

Animals↗
PubMed1993

Determination of safrole, dihydrosafrole, and chloromethyldihydrosafrole in piperonyl butoxide by high-performance liquid chromatography.

An HPLC method for the simultaneous determination of safrole (S), dihydrosafrole (DHS), and chloromethyldihydrosafrole (CM-DHS) in piperonyl butoxide, with fluorimetric detection and elution gradient, is described. Samples with internal standard (piperonyl isobutyrate) are adsorbed on silica cartridges, then eluted with an appropriate solvent. Internal standard, S, DHS, and CMDHS are eluted together and injected into a reversed-phase chromatography column. The concentrations of the three products are calculated from calibration graphs, and linearity and reproducibility are verified. The limit of detection is 2 mg.kg-1. This analytical method allows for control of the synthesis process of piperonyl butoxide and determination of some carcinogenic substances, such as S and DHS.

Chromatography, High Pressure Liquid↗
PubMed2006

Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: new lead-agents with analgesic and antipyretic properties.

In this work, we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5-yloxy)-acetylhydrazone derivatives (3), designed exploring molecular hybridization and isosteric replacement approaches between nimesulide (1) and carbanalogue NAH series (2) developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (4) as starting material. The evaluation of the antinociceptive properties of this series led us to discover a new potent prototype of analgesic and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which showed to be more potent than dipyrone used as standard.

Analgesics↗
PubMed1999

Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole.

In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A2 receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant Brazilian natural product, which occurs in Sassafras oil (Ocotea pretiosa). The results from preliminary evaluation of these novel aryl-sulfonamide compounds by the platelet aggregation inhibitory test, using rabbit PRP, induced by ADP, collagen, arachidonic acid, and U46619, identified the N-[2-(4-carboxymethoxyphenyl)ethyl]-6-methyl-3,4-methylenedioxyphe nyl- sulfonamido derivative as the most active among them, presenting in IC50 value for the U-46619-induced platelet aggregation in rabbit platelet-rich plasma: 329 microM.

Animals↗
PubMed1999

Studies on antiplatelet agents from natural safrole. II. Synthesis and pharmacological properties of novel functionalized oxime O-benzylether derivatives.

In an ongoing research program aiming at the synthesis and pharmacological evaluation of new possible prototype candidates exploring the molecular hybridation and bioisosterism principles for molecular designing, we describe in this paper the design and synthesis of a series of new functionalized oxime O-benzylethers (4a-b) and (14a-b) as antiplatelet agents based on the inhibition of arachidonic acid (AA) cascade enzymes. For the synthesis of these new bioactive derivatives we used safrole (5), a Brazilian abundant natural product, as starting material. The platelet anti-aggregating evaluation of these oxime O-benzylether compounds (4a-b) and (14a-b) in model induced by ADP, collagen and AA, has permitted to evidence an antithrombotic profile to these new derivatives, being the most active the derivative methyl [[3,4-methylenedioxyphenyl]methylene]amino]oxy]-4-methylenephenylacet ic acid (14a).

Animals↗
PubMed1996

Cytogenetic effects of piperonyl butoxide and safrole in CHO-K1 cells.

Recently, hepatocarcinogenicity in rats and mice was reported with regard to the methylenedioxyphenyl compound, piperonyl butoxide (PB), which is used as a synergist for pyrethrins and related insecticides. Induction of sister-chromatid exchanges (SCEs) and chromosomal aberrations (CAs) due to PB were investigated using CHO-K1 cells with or without rat liver S9 fraction (S9); at the same time, the effects of safrole (SF), a methylenedioxyphenyl compound and a weak hepatocarcinogen, were also examined. PB (0.25 and 0.3 mM) and SF (0.8 mM) caused a slight but significant increase in SCEs followed by a cell-cycle delay in the 3-h treatment without S9. In the presence of S9 (4.5%), the cytotoxicity of PB or SF was weakened greatly or slightly, the top dose capable of cell division was raised to 0.6 mM (2-fold) or 1 mM, respectively. PB with S9 induced SCE at doses of 0.4 and 0.5 mM, and caused endoreduplications (ERDs, 7%) at a dose of 0.6 mM, while SF caused a dose-related significant increase in SCE at all doses used (0.4-1 mM) with S9. Genotoxicity of the metabolites of PB or SF was cleared by changing the dose of S9 (1.5-9%) while holding the dose of each chemical constant. In the case of SF (0.6 mM), induction of SCE, ERD and cell-cycle delay intensified almost in a dose-effect relationship, and CAs and a high level of ERD (14%) were caused by a 9% dose of S9. The concentration of unchanged SF in the incubated medium was certainly in inverse proportion to the dose of S9. This strongly suggests that the metabolites of SF are genotoxic. In the case of PB (0.3 mM), no positive responses were produced in the cultures, even with a high level of S9, though the amount of unchanged PB left in the incubated medium was very slight. This indicates that the metabolites of PB may not be genotoxic. In conclusion, PB and SF are possible to somewhat induce SCE at high dose(s) in the absence of S9, and the genotoxic effects of SF are more intensified in the presence of S9 than in its absence, while PB is probably no genotoxic in the presence of sufficient metabolic activation.

Animals↗