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Effect of Boiling on the Content of Ascorbigen, Indole-3-carbinol, Indole-3-acetonitrile, and 3,3 '-Diindolylmethane in Fermented Cabbage
Abstract
The aim of the study was to investigate the effect of the boiling process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. The cabbage was boiled for 5 to 60 min. Boiling resulted in a decrease of the total content of the compounds analysed. The changes were mainly caused by leaching of ascorbigen predominating in cabbage into cooking water and by its thermal hydrolysis. Ascorbigen losses resulting from thermal hydrolysis accounted for 30% after 10 min of boiling and for 90% after 60 min of boiling. One of the ascorbigen breakdown products was indole 3 carbinol; the decrease in ascorbigen content was accompanied by a drastic increase in the content of 3,3'-diindolylmethane, a condensation product of indole-3-carbinol. After 40 and 50 min of boiling, the total content of 3,3'-diindolylmethane in cabbage and cooking water was approximately 0.2 micromol/100 g and was 6-fold higher than that in uncooked cabbage. 3,3'-Diindolylmethane synthesis proceeded within the plant tissue. After 10 min of boiling, the content of free indole-3-carbinol and indole-3-acetonitrile stabilized at the level of about 80% as compared to the uncooked cabbage.
... The chromatographic purity (HPLC) of the obtained compound reached 98.4%. 3,3'-diindolylmethane was synthesized from indole and formaldehyde according to the method proposed by Buskov et al. (2000) and described by Ciska, Verkerk, and Honke (2009). The chromatographic purity (HPLC) of the obtained compound reached 99.6%. ...
... Verkerk and Dekker (2004) observed higher concentrations of GLS (by up to 60%) in microwaved than in raw red cabbage. According to Ciska et al. (2009), the increase in total GLS levels in the first min of cooking could result from the degradation of plant tissue under exposure to heat because GLS in plant cells can partially bond to the cell wall and be released only after the cell structure disintegrates. Consequently, significantly higher GLS concentrations after 5 min of boiling could be attributed to more effective extraction from plant material after hydrothermal treatment. ...
... For this reason, plant material should be subjected to short hydrothermal pre-treatment by boiling in water or microwaving (Verkerk & Dekker, 2004) to determine the GLS content of fresh vegetables. Pre-treated samples would then be extracted with 70% methanol to determine the content of GLS (Commission of the European Communities, 1990) and with the appropriate organic solvents to determine the content of aliphatic and indole derivatives of GLS (Chiang et al., 1998;Ciska et al., 2009). The concentrations of various GLS in the plant material would be estimated based on the total stoichiometric concentrations of GLS and GLS breakdown products. ...
A B S T R A C T This study identified glucosinolate (GLS) breakdown products and determined the relationships between such products and parent GLS in boiled Brussels sprouts. This is the first ever study to analyse all groups of GLS breakdown products (aliphatic, aralkyl and indole) in boiled vegetables. In the examined boiled Brussels sprouts, isothiocyanates were not determined in the edible parts or cooking water. The presence of seven breakdown products was determined as indole-3-acetonitrile, indole-3-carbinol, ascorbigen and 3,3'-diindolylmethane released form glucobrassicin, 3-butenylnitrile released from sinigrin, 4-methylsulfinylbutanenitrile released from glucoiberin, and 2-phenylacetonitrile released from gluconasturtiin. In the edible parts, the content of indole-3-acetonitrile and 3-butenylnitrile was particularly high at approximately 30 and 16 mol/100 g FW, which was equivalent to 54 and 9% of the initial value of the parent GLS, respectively.
... From here, upon tissue damage, myrosinase converts glucobrassicin to 3-indolylmethylisothiocyanate, which is unstable and hydrolyzes to form indole-3carbinol [37]. Indole-3-carbinol is itself a potent organosulfur compound, which will be discussed further in this review, but it can also undergo acid condensation in the stomach to form 3,3-diindolylmethane [38] (Figure 3). ...
... Nutrients 2024, 16, 802 5 of 29 further in this review, but it can also undergo acid condensation in the stomach to form 3,3-diindolylmethane [38] (Figure 3). ...
This work represents an overview of the current investigations involving organosulfur compounds and colorectal cancer. The molecules discussed in this review have been investigated regarding their impact on colorectal cancer directly, at the in vitro, in vivo, and clinical stages. Organosulfur compounds may have indirect effects on colorectal cancer, such as due to their modulating effects on the intestinal microbiota or their positive effects on intestinal mucosal health. Here, we focus on their direct effects via the repression of multidrug resistance proteins, triggering of apoptosis (via the inhibition of histone deacetylases, increases in reactive oxygen species, p53 activation, β-catenin inhibition, damage in the mitochondrial membrane, etc.), activation of TGF-β, binding to tubulin, inhibition of angiogenesis and metastasis mechanisms, and inhibition of cancer stem cells, among others. In general, the interesting positive effects of these nutraceuticals in in vitro tests must be further analyzed with more in vivo models before conducting clinical trials.
... Some researchers have reported that indole-3-carbinol is abundant in cruciferous vegetables because it is derived from indole-3-glusosinolate (I3G), which is found in cabbage, broccoli, kale, cauliflower, and turnip. It has been proved that consumption of cabbage juice is beneficial as an antioxidant [13] and as an anti-cancer agent [14,15]. ...
... HPLC reverse-phase C 18 has been widely used for gluconsinolate determination [13,25,26,27,28]. A Waters PAH C 18 (250×4.6 ...
Indole-3-carbinol is a potential anti-cancer agent, and it has been found rich in Brassica vegetables. However, there was few good extraction method of indole-3-carbinol in cabbage and broccoli. In this work, the wavelength and the ration of mobile phase in determination method, as well as different temperature and pH values in extraction method were all investigated some cultivars of cabbage and broccoli were collected and validated the determination method. A sensitive and rapid high-performance liquid chromatography method has been established and used for the determination of indole-3-carbinol in cabbage (Brassica oleracea L. var. capitata) and broccoli (Brassica oleracea L. var. italica). The method was proved to be sensitive, selective, rapid and reproducible, with a good recovery of 99.25%. There was a fast retention time (4.88 min) and good linearity (R 2 =0.9991) in the system. Meanwhile, significant differences of indole-3-carbinol contents were detected among all the materials (P<0.05). Finally a simple extracting method of indole-3-carbinol was established, at the same time, the determination method was shown accurate, reliable and stable. So the determination method could be proposed application in medical and industrial area.
... In experimental models, I3C has been shown to self-condense to produce DIM at a ratio of 2:1. 24 DIM concentrations rise during cooking, 25 in part because of the thermal activation of myrosinase. This is evidenced by a 6-fold increase in DIM concentrations in boiled cabbage compared with uncooked cabbage. ...
... This is evidenced by a 6-fold increase in DIM concentrations in boiled cabbage compared with uncooked cabbage. 25 After ingestion, DIM concentrations in different tissues Figure 1 Metabolism of diindolylmethane from cruciferous vegetables. Diindolylmethane is an end product of the pH-dependent metabolism of indole-3-carbinol. ...
Diet is a modifiable factor associated with the risk of several cancers, with convincing evidence showing a link between diet and breast cancer. The role of bioactive compounds of food origin, including those found in cruciferous vegetables, is an active area of research in cancer chemoprevention. This review focuses on 3,3'-diindolylmethane (DIM), the major bioactive indole in crucifers. Research of the cancer-preventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.
... Chromatographic purity (HPLC) of the compound obtained reached 98.4%. 3,3 0 -Diindolylmethane was synthesized from indole and formaldehyde according to as described earlier (Ciska, Verkerk, & Honke, 2009). Chromatographic purity (HPLC) of the compound obtained reached 99.6%. ...
... Ascorbigen. The analysis was carried out according to the method described by Ciska et al. (2009) with slight modifications. Briefly, triplicates of non-stored or stored cabbage (10 g) were homogenised with 10 ml of water, using an Ultra Turrax Homogenizer (Janke & Kunkel, Germany). ...
... 10 To make it more combustible, EFB has to be shredded and dehydrated to moisture content below than 50%. 10 [40][41][42][43][44][45] Hemicellulose (mostly xylan) 9, 19-20 [19][20][21] Lignin 9, 19 18-21 ...
... These transformations and the subsequent rearrangements have been studied in more detail [44]. Generally, the decomposition reactions are quite dependent on pH and temperature and generally provide rather complex, multi-component product mixtures [45]. ...
Oil palm empty fruit bunch (EFB) fibers were subjected to solvolytic liquefaction to convert into liquid products using ethylene glycol (EG) as a supporting agent. The process was carried out at 250°C for 60 min. The water-insoluble product fraction was exhaustively extracted with acetone (ASL fraction) to separate all less polar. FTIR and comparative analytical pyrolysis GC/MS of the parent EFB fiber and the ASL fraction confirmed the formation of larger amounts of long-chain lipophilic compounds under liquefaction conditions. Furthermore, a considerable amount of less polar thermal lignin degradation products were obtained comprising all of the three main lignin building blocks, i.e. 4-hydroxyphenyl-(P units), 4-hydroxy-3-methoxyphenyl-(G units) and 3,5-dimethoxy-4-hydroxyphenyl (S units) substituted compounds. 4-Prop-2-en-1-yl substituted phenolic compounds contributed mostly to the cumulated peak area of all lignin derived pyrolysis products obtained by analytical Curie point pyrolysis GC/MS at 600C. The results of both instrumental-analytical methods confirm the formation of phenol and its derivatives, furan derivatives, organic acids, hydrocarbon, ester, benzene groups and alcohols.
... Both women and the health service would benefit from the existence of an effective natural medical treatment (using an oral preparation) for low-grade cytological lesions that would increase regression and reduce the need for excision. Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are found in cruciferous vegetables (Ciska et al, 2009) and have been identified as compounds that could potentially prevent or halt carcinogenesis (Bradlow, 2008; Ahmad et al, 2010). Diindolylmethane is naturally formed from I3C during acid digestion of cruciferous vegetables and I3C supplements (Reed et al, 2006; Ciska et al, 2009). ...
... Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are found in cruciferous vegetables (Ciska et al, 2009) and have been identified as compounds that could potentially prevent or halt carcinogenesis (Bradlow, 2008; Ahmad et al, 2010). Diindolylmethane is naturally formed from I3C during acid digestion of cruciferous vegetables and I3C supplements (Reed et al, 2006; Ciska et al, 2009). It has been shown that DIM acts directly to cause apoptosis in human breast, endometrial, cervical, ovarian, prostate, and colon tumour cells in culture (Ge et al, 1996; Bonnesen et al, 2001; Chen et al, 2001; Hong et al, 2002; Nachshon- Kedmi et al, 2004; Azmi et al, 2008). ...
Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities.
We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality.
Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated.
The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.
... (3 times) with a time interval of 10 min. in each cycle as described previously [15]. ...
Murraya koenigii (curry leaves) is a culinary spice rich of several bioactives. Many green extraction processes have recently been developed to isolate bioactives from herbs and spices. However, selecting an ideal extraction method to prepare an optimum extract rich in polyphenols and other bioactives is essential. Here, we have performed seven different extraction methods: ultrasonic-assisted extraction, maceration, cold extraction, soxhlet, microwave-assisted extraction (MAE), percolate, and homogenate to extract bioactives from curry leaves. We found that different extraction methods at various conditions influence the yield of bioactives, which can alter their bioactivity, such as antioxidant and anticancer properties. Among the extractions, microwave-assisted curry leaf extract (MA-CLE) yielded the highest content of phenols and flavonoids; thereby, MA-CLE has shown a higher antioxidant capacity than other extracts. Hence, we have selected MA-CLE for further study, where several bioactives, such as glycoside-bound flavonoids, terpenoids, and alkaloids, were identified through LC–MS/MS analysis. We found through RP-HPLC that MA-CLE is rich of resveratrol, rutin, coumarin, vallinic acid, and gallic acids. Among them, resveratrol was found to be the highest in MA-CLE. As MA-CLE is rich of several bioactives and has also shown greater antioxidant activity, further we have investigated the anticancer properties of MA-CLE against different cancer cells, including breast, lung, ovarian, and melanoma. We found that MA-CLE is a potent anticancer agent, predominantly against lung cancer, over other cancer cells. Overall, we found MAE can improve the phytochemical content and enhance the functional properties of curry leaf extract.
Graphical abstract
... Due to the fact that I3C was thermally unstable and polymerized easily after a long period of heating, the content was significantly (P < 0.05) lower at the 30-180 s treatment. A previous study reported that due to its thermal instability, the amount of I3C detected in boiling water and cabbage decreased with time within 30 min before plateauing, while the amount of DIM continued to rise for 50 min (Ciska, Verkerk, & Honke, 2009). As a result, we suspected that I3C might convert into DIM and LTr1 at higher microwave powder and longer time conditions. ...
Appropriate processing and cooking technologies can effectively improve the content of bioactive compounds in vegetables. The effects of microwave bag cooking on broccoli floret quality attributes, glucosinolates (GLSs) content and hydrolysate production were investigated in this study. Microwave bag cooking not only preserved the color of the florets, but also enhanced the total phenolic and flavonoid content, as well as total chlorophyll and ascorbic acid content. Furthermore, the majority of the microorganisms were inactivated, and the structure of the florets was greatly destroyed, thereby increasing antioxidant capacity and promoting the release of GLSs and myrosinase activity in the florets. Moreover, microwave bag cooking significantly enriched the sulforaphane (SFN) and indole-3-carbinol (I3C) production of broccoli florets in the meantime, demonstrating that it was a convenient and quick cooking option to satisfy the requirements of modern consumers.
... The high nutritional value of sauerkraut is attributed to the presence of carbohydrates and dietary fiber as the primary constituents, as well as the presence of vitamin C. Cabbage, is utilized in the preparation of Sauerkraut and contains a high concentration of phytochemicals, which include phenolic compounds and glucosinolates (GLS). [29] For enhancing nutritional profile, glucosinolates (GLS) play an important role by providing flavor and odor due to various metabolites. [30] The environmental conditions and postharvest processing can affect the nutritional profile and content of GLS. ...
Sauerkraut is a traditional fermented vegetable product that has numerous health endorsing properties. It is produced by spontaneous fermentation of cabbage that mainly involves heterofermentative lactic acid bacteria. The amount of salt introduces influences the physiochemical, microbial load, and also sensory consistency of sauerkraut. Sauerkraut has a high nutritional and phytochemical profile as well as has some epidemiological attributes. Sauerkraut is rich in vitamins and phenolic compounds, which protect against oxidative stress by serving as powerful free radical scavengers. The sauerkraut is being considered one of the best functional foods across the world due to its therapeutic potential. The current review provides an overview of production technology, nutritional, phytochemical, and different therapeutics (chemo preventive, antioxidant, anti-inflammatory) aspects of sauerkraut.
... italica Plenck (synonym of Brassica cretica Lam.)) , and cabbage (Brassica oleracea var. capitata L. (synonym of Brassica oleracea L.)) (Ciska, Verkerk, and Honke 2009). Literature suggested that green tea and black tea (Camellia sinensis (L.) Kuntze) (Gensler et al. 1996;Kumar et al. 2019) are the major sustainable bioresources for epigallocatechin gallate, but other resources like Terminalia bellirica (Gaertn.) ...
Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental
factors lead to BC development and on this basis, several preventive – screening and therapeutic
interventions have been developed. Hormones, both in the form of endogenous hormonal signaling
or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top
of these, breast microbiota includes both species with an immunomodulatory activity enhancing
the host’s response against cancer cells and species producing proinflammatory cytokines associated
with BC development. Identification of novel multitargeted therapeutic agents with
poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing
body of research has emphasized the potential of natural compounds derived from medicinal
plants and microbial species as complementary BC treatment regimens, including dietary
supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile,
Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet &
B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and
Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05
have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in
tumors’ chemosensitivity, antioxidant activity and modulation of BC – associated molecular pathways.
Further, bioactive compounds like 3,3’-diindolylmethane, epigallocatechin gallate, genistein, rutin,
resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest
for the researchers and clinicians because these natural agents have multimodal action and act
via multiple ways in managing the BC and most of these agents are regularly available in our
food and fruit diets. Evidence from clinical trials suggests that such products had major potential
in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects.
We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings
of medicinal plants and microbial metabolites in BC management. The future perspectives on the
translation of these findings to the personalized treatment of BC are provided and discussed.
... However, a drastic increase in 3,3′-diindolylmethane level was observed likely derived from the condensation of indole-3-carbinol detected at 6-folds higher level than that in raw cabbage (E. Ciska, Verkerk, and Honke 2009), and to rationalize for the decline in indole-3-carbinol upon heat processing. ...
Red and white cabbages (Brassica oleracea var. capitata f. rubra and alba, respectively) are two of the most commercially valued vegetables in crucifers, well-recognized for their unique sensory and nutritive attributes in addition to a myriad of health-promoting benefits. The current review addressed the differential qualitative/quantitative phytochemical make-ups for the first time for better utilization as nutraceuticals and to identify potential uses based on the chemical makeup of both cultivars (cvs.). in addition, extraction methods are compared highlighting their advantages and/or limitations with regards to improving yield and stability of cabbage bioactives, especially glucosinolates. Besides, the review recapitulated detailed action mechanism and safety of cabbage bioactives, as well as processing technologies to further improve their effects are posed as future perspectives. white and red cabbage cvs. revealed different GLSs profile which affected by food processing, including enzymatic hydrolysis, thermal breakdown, and leaching. in addition, the red cultivar provides high quality pigment for industrial applications. Moreover, non-conventional modern extraction techniques showed promising techniques for the recovery of their bioactive constituents compared to solvent extraction. All these findings pose white and red cabbages as potential candidates for inclusion in nutraceuticals and/or to be commercialized as functional foods prepared in different culinary forms.
... Most literature data concern mature Brassica vegetables or sprouts, but not plants in other vegetative stages, such as young shoots. The results obtained by Ciska et al. [20] for the total content of glucosinolates in different red cabbages at full maturity depending on the year of harvest. Different results were attributed to climatic factors like rainfall and temperature during the growing period. ...
Most literature data indicate that the diet rich in plant products reduces the risk of developing chronic non-communicable diseases and cancer. Brassica vegetables are almost exclusively synthesizing glucosinolates. Glucosinolates are higher in sprouts than in mature plants, being related to the activity of the specific myrosinase involved in the degradation of glucosinolates during developmental stages. This study compares the content of total glucosinolates with their profile and, rare in the literature, also with products of their degradation. Average amounts of total glucosinolates in young shoots of white and red headed cabbage were 26.23 µmol/g d.m. and 27.93 µmol/g d.m., respectively. In addition, antioxidative properties of 21-day-old shoots of white and red headed cabbage were assessed. The area of negative peaks after post-column derivatization with the ABTS reagent, indicating antioxidant activity of young red cabbage shoots, was 20185, compared to the value determined for young white cabbage shoots (3929). The results clearly indicate that, regardless of the vegetable species, young shoots of white and red headed cabbage can be an important source of bioactive substances in the diet, thus being an important element of cancer chemoprevention.
... 3 The well-known metabolite 3,3-diindolylmethane (DIM) is generated during the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables including broccoli, cabbage, and kale. 4,5 Previous studies have revealed that DIM is an antiinflammatory compound 6 that exerts preventive and therapeutic effects against various human colorectal cancers as well as experimental colitis in mice. 7−10 The detailed molecular and immunological mechanism underlying the preventive effects of DIM against colorectal cancer and IBDs has been elucidated using a cultured colon cancer cell model 8,11 and an in vivo mouse model, 9,10 respectively. ...
3,3'-Diindolylmethane (DIM), a digestive metabolite originating from cruciferous vegetables, has dietary potential for the treatment of various human intestinal diseases. Although intestinal permeability dysfunction is closely related to the initiation and progression of human intestinal inflammatory diseases (IBDs), the effect of DIM on intestinal permeability is unclear. We evaluated the effect of DIM on the intestinal permeability of human intestinal cell monolayers and the animal model Caenorhabditis elegans, which were treated with IL-1β and Pseudomonas aeruginosa, respectively, to mimic IBD conditions. DIM substantially restored the intestinal permeability of differentiated Caco-2 cells by enhancing the expression of tight junction proteins (including occludin and ZO-1). Compared to the IL-1β single treatment (551.0 ± 49.0 Ω·cm2), DIM (10 μM) significantly increased the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers (919.0 ± 66.4 Ω·cm2, p < 0.001). DIM also ameliorated the impaired intestinal permeability and extended the lifespan of C. elegans fed P. aeruginosa. The mean lifespan of DIM-treated worms (10.8 ± 1.3 days) was higher than that of control-treated worms (9.7 ± 1.1 days, p < 0.01). Thus, DIM is a potential nutraceutical candidate for the treatment of leaky gut syndrome by improving intestinal permeability.
... Ascorbigen is considered to be predominant in sauerkraut. The level of ascorbigen varies from 6.5 to 16 (mmol/100 g), depending on the starter cultures and other conditions of fermentation (Ciska, Verkerk, & Honke, 2009;Martinez-Villaluenga et al., 2009). The composition of fatty acids also changes during the ensiling process in association with the oxidation and biohydrogenation of unsaturated fatty acids (Alves, Cabrita, Jerónimo, Bessa, & Fonseca, 2011;Łozicki et al., 2015). ...
The effects of 10 and 20 days of fermentation followed by freeze-drying on the vitamin C and fatty acids contents, chemical conversions and overall chemical composition of Jerusalem artichoke were studied. Fermentation between the 10th and 20th days increased content of all saturated fatty acids and two of the four unsaturated fatty acids. The only fatty acid content that decreased was that of C18:1 cis 9 acid, which was suggested to be converted to other fatty acids. The experimental data, which were supported by energetical feasibility, suggested the reaction pathways of the mutual conversions of fatty acids and confirmed the decreased vitamin C content during fermentation. Discriminant modelling of the spectral data successfully distinguished the fresh, 10 days and 20 days fermented samples. The correlation of the spectral and reference data allowed to construct reference models for predicting the content of vitamin C and C18:1 cis 9 fatty acid.
... Breast cancer survivors frequently self-prescribe bioactive dietary supplements with the intention to obtain survival benefit [5][6][7][8]. Of these, 3,3 0 -diindolylmethane (DIM), a stable in vivo metabolite of indole-3-carbinol (I3C) found in cruciferous vegetables [9], is among the most well studied [10]. We previously reported, from a secondary analysis, a 52% reduction in breast cancer recurrence among women consuming more cruciferous vegetables [11] hypothesized to be attributed to higher exposure to indolyl-3-carbinol and the related dimer, DIM [12,13]. ...
Purpose:
Diindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen.
Methods:
Women prescribed tamoxifen (n = 130) were randomly assigned oral BR-DIM at 150 mg twice daily or placebo, for 12 months. The primary study endpoint was change in urinary 2/16α-hydroxyestrone (2/16α-OHE1) ratio. Changes in 4-hydroxyestrone (4-OHE1), serum estrogens, sex hormone-binding globulin (SHBG), breast density, and tamoxifen metabolites were assessed.
Results:
Ninety-eight women (51 placebo, 47 DIM) completed intervention; compliance with treatment was >91%. BR-DIM increased the 2/16α-OHE1 ratio (+3.2 [0.8, 8.4]) compared to placebo (-0.7 [-1.7, 0.8], P < 0.001). Serum SHBG increased with BR-DIM compared to placebo (+25 ± 22 and +1.1 ± 19 nmol/L, respectively). No change in breast density measured by mammography or by MRI was observed. Plasma tamoxifen metabolites (endoxifen, 4-OH tamoxifen, and N-desmethyl-tamoxifen) were reduced in women receiving BR-DIM versus placebo (P < 0.001). Minimal adverse events were reported and did not differ by treatment arm.
Conclusion:
In patients taking tamoxifen for breast cancer, daily BR-DIM promoted favorable changes in estrogen metabolism and circulating levels of SHBG. Further research is warranted to determine whether BR-DIM associated decreases in tamoxifen metabolites, including effects on endoxifen levels, attenuates the clinical benefit of tamoxifen.
Trial registration:
ClinicalTrials.gov NCT01391689.
... I3C and indol-3-acetonitrile (I3A) have also been detected in sauerkraut at concentrations of 0.13-0.94 μmol/100 g fw and 0.07-0.25 μmol/100 g fw, respectively (Tolonen et al., 2002;Ciska et al., 2009;Ciska and Honke, 2012;Peñas et al., 2012a,b;Palani et al., 2016). It should be highlighted that the addition of sodium selenite (0.3 mg/kg fw) has been found to be beneficial to enhance the concentration of both compounds in sauerkraut (Peñas et al., 2012a,b). ...
Sauerkraut is a traditional vegetable product usually produced by spontaneous fermentation that relies on lactic acid bacteria (LAB) naturally present in white cabbage. However, current trends on sauerkraut production propose the application of starter cultures in order to ensure a uniform quality of the product. Besides its high nutritional value, there are numerous in vitro investigations and some epidemiological data suggesting the potential positive effects of sauerkraut on health. These health-promoting properties are supported by strong evidence obtained from experimental studies, demonstrating that specific phytochemicals of sauerkraut have antioxidant, antiinflammatory, and a chemopreventive action against certain types of cancer. This chapter provides an overview of the production process of sauerkraut and its nutritional and phytochemical composition. The scientific data supporting the health benefits of sauerkraut will be also reviewed.
... A wealth of preclinical evidence supports the anticancerogenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables [4]. Numerous in vitro and in vivo studies have shown that the breakdown products of indole and aliphatic GLS have anticarcinogenic properties [5,6], particularly on breast, colon, prostate cancer [7]. ...
Encapsulation with PLGA of I3C and radioiodination have been performed. Anticancerogenic effects of I3C and I3C-PLGA have been investigated utilizing in vitro methods on breast adenocarcinoma epithelial (MCF7), colon adenocarcinoma epithelial (Caco2), prostate carcinoma epithelial (PC3) cells. Characterization of I3C-PLGA have been performed with DLS method and SEM analysis. I3C and I3C-PLGA compounds have been radiolabeled in high yields with 131I which is widely used for diagnosis and treatment in Nuclear Medicine. All experimental results demonstrated that radioiodinated compounds are promising in order to be used in Nuclear Medicine as well as present study contributed previously reported studies.
... This agrees with the findings of other authors (De Vos and Blijleven 1988), who did not detect the products of the GLS breakdown in the cooked brassica vegetables. Ciska et al. (2009) was to investigate the effect of the boiling process on the content of ascorbigen, I3C, I3ACN and 3,3 0 -diindolylmethane in fermented cabbage. After 10 min of boiling, the content of free I3C and I3ACN stabilized at the level of about 80% as compared with the uncooked cabbage, but after 40 and 50 min of boiling, the total content of 3,3 0 -diindolylmethane in cabbage was sixfold higher than that in uncooked cabbage. ...
Kale has a great nutritive value, very high antioxidant activity and pro-healthy potential. The level of phytochemicals and related bioactive compounds are strongly dependent on pre and postharvest stages of production chain (domestic or industrial). The study investigated changes in the levels of vitamin C, β-carotene, total polyphenols, antioxidant activity, degradation products of glucosinolates as well as nitrates and nitrites in the kale due to the conventional cooking process. As a result of cooking kale, a significant decrease was noted in the content of vitamin C, polyphenols, diindolilometan, indole-3-acetic acid and nitrate and nitrites, and a significant growth in the content of β-carotene, indole-3-carbinol, indole-3-acetonitrile, total indoles and total isothiocyanate compared with the raw vegetable. It has been found that kale, fresh and cooked, had similar antioxidative potential. Practical Applications: Brassica species are commonly occurring in a diet as an additive to meat dishes and other rich-in-fat products, which favor tumor transformation. Due to their high consumption and availability over the whole year, brassicas may potentially be a crucial element in chemoprevention of cancer. The weakness of vegetables is their seasonal availability and fact that they are perishable. During processing of these vegetables for food preparation the most commonly used technique is cooking. Food technology is focused on discovering and establishing the methods of food processing, which will least affect their chemical composition. It is very important to know how to optimize, e.g., conventional cooking process to preserve beneficial and bioactive compounds of vegetables.
... The authors also suggested that when the myrosinase underwent denaturation during the boiling of vegetables, the glucobrassicin might have undergone further transformations, but nitriles could also have formed through nonenzymatic decomposition of glucosinolates. Ciska, Verkerk, and Honke (2009) reported that after 40 and 50 min of boiling of fermented cabbage, the total content of 3,3′-diindolylmethane was 6-fold higher than that in uncooked vegetable. 3,3′-Diindolylmethane synthesis proceeded within the plant tissue. ...
Changes in the levels of glucosinolates and their degradation products in selected Brassica vegetables due to the cooking process were investigated. The purple cauliflower was found to be the best source of aliphatic and indole glucosinolates, and it was also abundant in compounds such as sinigrin, glucoraphanin and glucobrassicin. As a result of cooking rutabaga, green cauliflower and purple cauliflower, a significant decrease was noted in total glucosinolates (6.6, 68.9 and 69.2%, respectively) compared to raw vegetables. The hydrothermal processing applied led to a decline in the sum of indoles and isothiocyanates of 48.5 and 11.0%, respectively, in green cauliflower; and of 75.8 and 42.4%, respectively, in purple cauliflower; whereas, in rutabaga it led to an increase of 142.9 and 329.4%, respectively, compared with raw vegetables.
... Iberin, iberin nitrile, allyl cyanide, allyl isothiocyanate, sulforaphane and ascorbigen can be found during cabbage fermentation (Martinez-Villaluenga et al. 2009; Peñas et al. 2012), among which ascorbigen is the predominant one found in sauerkraut. It is synthesis product of indol-3- carbinol and ascorbic acid in acidic conditions and has been identified in concentration range of 6.5–16 lmol/100 g fw upon natural NaCl fermentation (Ciska et al. 2009; Martinez-Villaluenga et al. 2009). Selection of appropriate starter cultures can increase ascorbigen content of sauerkraut and its nutritional value (Martinez-Villaluenga et al. 2012). ...
White cabbage (Brassica oleraceae var. capitata f. alba) is a cruciferous vegetable used worldwide as a food and in traditional medicine. Due to its common availability in local markets, affordability, and consumer preference, it represents a significant source of phytonutrients in the human diet. This review provides an overview of white cabbage origin, taxonomy, geographical distribution, botanical characteristics, and contemporary and traditional uses, as well as its phytochemicals and pharmacology. Special emphasis is placed on a health-promoting phytochemicals such as glucosinolates, polyphenols, and vitamins, as well as anticancerogenic, antioxidant, anti-inflamantory and cardioprotective effects. The majority of so far published research on white cabbage was focused on qualitative determination of phytochemicals (targeted analysis), while only few recent papers published data based on untargeted metabolomic profiling. Hence, this review discusses and emphasizes a further need of studying the white cabbage phytochemicals using modern metabolomics platforms which will enable scientists to pinpoint the exact bioactive metabolites which are responsible for certain bioactivity.
... These transformations and the subsequent rearrangements have been studied in more detail [44]. Generally, the decomposition reactions are quite dependent on pH and temperature and generally provide rather complex, multi-component product mixtures [45]. ...
Ascorbigen (2-C-(3-indolyl)-methyl-α-L-xylo-hex-3-ulofuranosono-1,4-lactone, 1) is a breakdown product of glucobrassicins found in cruciferous vegetables, such as cabbage, cauliflower, Brussel sprouts, or broccoli, formed by direct C-alkylation of ascorbic acid (vitamin C) by (3-indolyl)-methyl intermediates under physiological conditions. It is a labile compound, and direct synthesis approaches are hampered by the oxidative instability of the indol moiety and ring transformations of the ascorbyl part. The latter have also impeded ascorbigen analytics for decades, and only recently different ascorbigens have been shown to represent mixtures of compounds rather than individual ascorbigen-type compounds. Following a review of pertinent literature, timely aspects of ascorbigen chemistry, including the most recent synthesis approaches and in-depth characterization of the compound, are presented.
... The EGFR pathway is recurrently activated in cancer cell, and its targeted inhibition with a small molecule kinase inhibitor has been successful for lung, breast and ovarian cancer with EGFR mutations (Yarden and Sliwkowski, 2001;Cataldo et al., 2011). 3,3'-diindolylmethane (DIM), an active metabolite of indole-3-carbinol, is present in cruciferous vegetables (Ciska et al., 2009). Several studies have indicated an inverse relationship between intake of cruciferous vegetables and the risk of ovarian cancer and also concluded that DIM possesses chemopreventive and therapeutic properties (Rahman and Sarkar, 2005;Kandala and Srivastava, 2010). ...
Epidermal Growth Factor Receptor (EGFR) is one of the four members of the Human Epidermal Receptor (HER)
family, which is
deregulated
and over expressed in platinum resistant ovarian cancer. Thus, targeting EGFR
receptor along with platinum drugs is one of the major strategies to increase the platinum drug sensitivity. That‟s
why, in this study, we aimed to investigate the inhibitory ac
tivity and binding site analysis of indole
-
3
-
carbinol
and its active metabolite 3,3'
-
diindolylmethane by using molecular simulation studies, also metabolic profile had
been investigated by SOM prediction. The 3,3'
-
diindolylmethane showed significant inhibi
tory activity and
binding energy comparing to indole
-
3
-
carbinol, also it processed lower toxicity and will undergo aromatic
hydroxylation due its high intrinsic activity and Fe accessibility. Though our research study supports previous
reports of EGFR inhi
bition, further in vivo study is necessary for validation of toxicological and pharmacokinetic
study. However, the current work tries to address most of the variables in the dynamic drug design process by
In
silico
study in order to boost the potentiality
of the selected molecule to serve as good leads in terms of optimum
pharmacokinetic and toxicological attributes.
In silico analysis of indole-3-carbinol and its metabolite DIM as EGFR tyrosine kinase inhibitors in platinum resistant ovarian cancer vis a vis ADME/T property analysis. Available from: https://www.researchgate.net/publication/285406327_In_silico_analysis_of_indole-3-carbinol_and_its_metabolite_DIM_as_EGFR_tyrosine_kinase_inhibitors_in_platinum_resistant_ovarian_cancer_vis_a_vis_ADMET_property_analysis [accessed Dec 26, 2015].
... These transformations and the subsequent rearrangements have been studied in more detail previously [21]. Generally, the neutral-to-alkaline decomposition reactions are quite dependent on pH and temperature, and generally provide an unstable, multi-component mix [31]. ...
1-(2-Furanyl)-2-(3-indolyl)ethanone (FIE, 4) is a potent ligand of the human aryl hydrocarbon receptor (AhR), the so-called dioxin receptor, and the estrogen receptors (ERs), with high activities in transactivation assays. Direct synthesis approaches towards 4 have been hampered by the high oxidative instability of both the indole moiety and the furan part. A biomemetic synthetic pathway was devised that provides the compound for the first time in gram amounts sufficient for comprehensive testing. In the first step, ascorbigen (11) - a breakdown product of glucobrassicins in cruciferous vegetables - is formed according to a rare example of direct C-alkylation of non-protected ascorbic acid (vitamin C) by (3-indolyl)-methyl intermediates under physiological conditions. Ascorbigen is then decarboxylated and rearranged to the target compound 4 under similarly mild conditions in the presence of zinc oxide on silica gel, providing 88% overall yield. The same reaction can be carried out without catalyst but at slightly elevated temperatures under carefully profiled microwave heating, though at somewhat decreased yields along this path (60%), i.e. 28% yield penalty. The thiophene analogue and pyrrol analogue of the target were synthesized according to the same protocol. The reaction conditions were thoroughly optimized, and all compounds were comprehensively analytically characterized, including complete NMR resonance assignment in the 1H-and 13C-domains, MS and pyrolysis-GCMS characterization, and X-ray crystal structure analysis of the thiophene derivative.
... This suggests that all DIM forms from I3C and conditions in all parts of the plants under study are promoting the condensation reaction to a similar extent. Different situation was described by Ciska et al. (2009) who observed lower I3C and higher DIM amounts in cooked fermented cabbage where the content of these compounds was respectively 0.85 and 1.70 nmol g −1 fw. These results are in agreement with the observations by Bradlow and Zeligs (2010) who suggested alleviated conversion of I3C into DIM under acidic conditions. ...
A high-performance liquid chromatographic method with UV and fluorescence detection (HPLC-DAD-FLD) was developed for simultaneous determination of indolic compounds in plant material. Indole-3-carbinol (I3C), indole-3-acetic acid (I3AA), indole-3-acetonitrile (I3ACN), and 3,3′-diindolylmethane (DIM) were used as representative compounds that cover a wide spectrum of indole structures occurring in nature. For concentration and purification of the analytes, a solid-phase extraction (SPE) pretreatment was used. The separation utilized a Zorbax XDB-C8 reversed-phase column, acetonitrile-water containing 0.01 % formic acid gradient and UV (280 nm) in series with fluorescence (ex. 280 nm; em. 360 nm) detection. Good linearities of calibration curves were found within the ranges of 0.1–100 nmol/mL for I3C and DIM, 0.4–100 nmol/mL for I3AA and I3ACN for UV detection and 0.003–10 nmol/mL for I3C, 0.003–5 nmol/mL for DIM, and 0.02–10 nmol/mL for I3AA and I3ACN for fluorescence detection. The lowest detection limits (LOD) for UV detection were 0.03 nmol/mL for I3C, 0.1 nmol/mL for I3AA and I3ACN, and 0.04 nmol/mL for DIM, while for fluorescence detection were 0.001 nmol/mL for I3C and DIM, and 0.006 nmol/mL for I3AA and I3ACN. The usefulness of HPLC-DAD-FLD method with SPE pretreatment is illustrated by the analysis of indolic compounds in extracts from different parts of Brassica vegetables.
... Cruciferous vegetables such as cauliflower, cabbage and broccoli are rich sources of glucosinolates (Higdon et al, 2007). Crushing or cooking these vegetables results in the formation of sulphurcontaining isothiocyanates and indole-based I3C and DIM (Higdon et al, 2007;Ciska et al, 2009). Under the acidic environment of the stomach, I3C further dimerises to the biologically active and stable DIM and its associated oligomers, collectively referred to as acid condensation products, which are believed to be responsible for most of the biological effects associated with I3C (Shertzer and Senft, 2000). ...
Background:
Haploinsufficiency may contribute to the development of breast cancer among women with a BRCA1 mutation. Thus, interventions that enhance BRCA1 expression may represent avenues for prevention. Studies have shown that 3,3'-diindolylmethane (DIM) can upregulate BRCA1 expression in breast cancer cells. This has yet to be demonstrated in vivo.
Methods:
We conducted a study to evaluate the ability of oral DIM to upregulate BRCA1 mRNA expression in white blood cells. A total of 18 women were enroled in the study, including 13 BRCA1 mutation carriers who received 300 mg per day of Rx Balance BioResponse DIM for 4-6 weeks (intervention group) and 5 BRCA1 mutation carriers who did not take DIM (control group). BRCA1 mRNA expression was assessed at baseline and at 4-6 weeks by real-time, quantitative PCR and the relative change in BRCA1 mRNA expression (that is, 2(-ΔΔCT)) was calculated.
Results:
The relative change in BRCA1 mRNA expression among women in the intervention group achieved borderline significance (P paired t-test=0.05). In the intervention group, BRCA1 mRNA expression increased in 10 of the participants, decreased in 2 and remained unchanged in 1 of the participants following DIM intervention (P sign test=0.02). On average, women in the intervention group experienced a 34% increase in BRCA1 mRNA expression (range -24 to 194%). There was no significant difference in the relative change in BRCA1 mRNA expression among women in the control group (P paired t-test=0.45).
Conclusions:
Under the tested conditions, oral DIM was associated with an increase in BRCA1 mRNA expression in women with a BRCA1 mutation. The possibility of mitigating the effect of an inherited deleterious BRCA1 mutation by increasing the physiologic expression of the gene and normalising protein levels represents a clinically important paradigm shift in the prevention strategies available to these high-risk women. Future studies with a larger sample size and higher doses of DIM are warranted.
... During natural fermentation, the content of indole GLS hydrolysis products markedly increased (P 6 0.05), ABG being the major indole GLS-derived compound found in NF cabbage (Table 1), followed by I3C, and I3ACN. The content of indole GLS-derived products in NF cabbage differed from that in previous studies (Ciska & Pathak, 2004;Ciska, Verkerk, & Honke, 2009;Martinez-Villaluenga et al., 2009; which could be attributed to differences in glucobrassicin concentration and myrosinase activity as they depend on genetic and environmental factors that vary among growing locations and year of cultivation (Peñas et al., 2011;Rosa, Hesney, Fenwick & Portas, 1997). ...
Selenium (Se) has a well-known role in prevention of chronic diseases associated with oxidative stress and inflammation. The objective was to produce Se-enriched sauerkraut and to study the effect of selenite addition on indole glucosinolate hydrolysis products, vitamin C, Se biotransformation and microbial quality. The antioxidant activity of sauerkraut and its ability to inhibit NO production in LPS-induced macrophages were also examined. White cabbage was naturally fermented with 0.3 mg of Na2SeO3/kg fresh cabbage (NFSe) or without Se addition (NF). Total Se content reached up to 1.29 μg/g d.m. (0.11 μg/g f.m.). Selenomethylselenocysteine was the major Se form found in NFSe cabbage. Se addition caused a slight reduction of ascorbigen (6%) and vitamin C (5%) contents in sauerkraut (P ⩽ 0.05); however, lactic acid bacteria increased (3%), and the formations of indole-3-carbinol and indole-3-acetonitrile were markedly enhanced (74% and 13%, respectively). NFSe cabbage extracts showed higher (P ⩽ 0.05) antioxidant activity (163 μmol trolox/g d.m.) and inhibition of NO production in LPS-induced macrophages (IC50 = 44.0 μg/ml) than did NF cabbage extracts. Consequently, Se-enriched sauerkraut can be considered as a health-promoting food.
... ABG was the most abundant indole GLS degradation compound (65 mmol/100 g d.m.), followed by I3C (17 mmol/100 g d.m.), while I3ACN was present in the lowest amount (3 mmol/100 g d.m.). The presence of these three compounds in just fermented cabbages is in the range reported previously (Ciska, Verkerk, & Honke, 2009;Peñas et al., 2012). In NF-HHP sauerkrauts produced with the highest NaCl level, the content of ABG (37 mmol/ 100 g d.m.) and I3C (13 mmol/100 g d.m.) was lower than in those obtained with the lowest salt concentration, while no difference was observed between the two NF-HHP sauerkrauts for I3ACN content. ...
... There are more than 15 different anthocyanins present in red cabbage , amounting to a total of 25 mg/100 g of red cabbage (Wang, Cao, & Prior, 1997). Although a number of reports exist in literature on Brassica oleracea L. (Ciska, Verkerk, & Honke, 2009; Llorach, Espi 9 n, TomäsBarberän, & Ferreres, 2003; Podse ˛ dek, 2007; Racchi et al., 2002 Contents lists available at ScienceDirect ...
Using different extraction protocols, the antioxidant properties of green and red cabbage extracts were evaluated in terms of the total antioxidant capacities using the 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulphonic acid) (ABTS) radical scavenging method. The results demonstrate that the total antioxidant capacity of green and red cabbages correlated well with the total phenolics and total flavonoids content present in the extracts. The ABTS radical scavenging capacity of red cabbage was much higher than that of green cabbage extract. Using time resolved absorption kinetic spectrophotometry, free radical reactions with the extracts of green and red cabbages were established. The reactions of extracts were examined using a pulse radiolysis technique. Kinetic studies indicated that extracts may act as free radical scavengers for O2-, OH radicals and as an antioxidant to repair free-radical damage to biologically important guanosine radical.
... From our study, I3C showed a much poorer thermal stability than DIM at 37 °C. Ciska, Verkerk, and Honke (2009) investigated the effect of boiling on the content of I3C and DIM in fermented cabbage. In their study, the content of I3C detected in both boiling water and cabbage decreased with boiling time within 30 min before reaching a plateau, due to its thermal instability; however, the DIM concentration kept increasing for 50 min. ...
... From our study, I3C showed a much poorer thermal stability than DIM at 37°C. Ciska, Verkerk, and Honke (2009) investigated the effect of boiling on the content of I3C and DIM in fermented cabbage. In their study, the content of I3C detected in both boiling water and cabbage decreased with boiling time within 30 min before reaching a plateau, due to its thermal instability; however, the DIM concentration kept increasing for 50 min. ...
Indole-3-carbinol (I3C) and 3, 3’-diindolylmethane (DIM) are two bioactive compounds from Cruciferous vegetables. The stability of these compounds is a major challenge for their pharmaceutical applications. In this study, zein and zein/carboxymethyl chitosan (CMCS) nanoparticles were prepared to encapsulate I3C and DIM by a combined liquid-liquid phase separation and ionic gelation method. After zein nanoparticles were coated with CMCS, the zeta potential was decreased from around ‒10 to ‒20 mV, and encapsulation efficiency was greatly improved. Both nanoparticle formulations provided controlled release of I3C and DIM in PBS medium. Zein and zein/CMCS nanoparticles demonstrated similar protection for both I3C and DIM against ultraviolet (UV) light, attributed mainly to the contribution of the zein protein. Compared with zein nanoparticles, zein/CMCS nanoparticles exhibited better protection of I3C against degradation and better inhibition against its oligomerization to DIM under thermal condition (37°C). Based on our results, the encapsulation of hydrophobic bioactives in zein/CMCS nanoparticles is a promising approach to improve their stability against harsh conditions and provide controlled release for food/pharmaceutical applications.
... 3,3'-Diindolylmethane (DIM), an active metabolite of indole-3-carbinol, is present in cruciferous vegetables [15]. Accumulating epidemiological evidence indicates an inverse relationship between intake of cruciferous vegetables and the risk of ovarian cancer [16]. ...
Signal transducer and activator of transcription 3 (STAT3) is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported previously that diindolylmethane (DIM) inhibits the growth of ovarian cancer cells. However, to date the exact mechanism by which DIM induces growth suppressive effects has not been clear. In this report the mode of action of DIM is investigated.
Six human ovarian cancer cell lines and an ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination with cisplatin.
Diindolylmethane treatment induced apoptosis in all six ovarian cancer cell lines. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. Interleukin (IL)-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, DIM treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. DIM treatment also inhibited cell invasion and angiogenesis by suppressing hypoxia-inducible factor 1α (HIF-1α) and vascular epithelial growth factor (VEGF). Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation.
These findings provide a rationale for further clinical investigation of DIM alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.
... Because EGFR is involved in various aspects of cancer growth, including tumor initiation, angiogenesis, and metastasis, it represents an attractive target for therapeutic intervention. 3,3-Diindolylmethane (DIM), an active metabolite of in- dole-3-carbinol, is present in cruciferous vegetables (Ciska et al., 2009 ). DIM is formed by the dimerization of indole-3- carbinol. ...
Genetic alterations, including the overexpression of epidermal growth factor receptor (EGFR) (in approximately 70% of ovarian tumors), play a crucial role in the signal transduction pathways that regulate key cellular functions, such as cell survival and proliferation, and are responsible for compromising traditional chemotherapy. 3,3'-Diindolylmethane (DIM) is an indole compound present in Brassica vegetables. In our previous studies, we demonstrated that BR-DIM, a formulated version of DIM, suppressed the growth of ovarian cancer cells by causing cell cycle arrest and apoptosis. In the present study, we delineated the mechanism by which DIM suppressed the growth of SKOV-3, OVCAR-3, and TOV-21G human ovarian cancer cells. DIM treatment caused significant down-regulation of the constitutive EGFR protein level as well as phosphorylation of EGFR at Tyr1068, Tyr992, Tyr845, and Tyr1173 in various ovarian cancer cells. To determine whether DIM suppressed the activation of EGFR by activating phosphorylation, cells were treated with epidermal growth factor. Epidermal growth factor treatment significantly blocked the DIM-mediated inhibition of EGFR activation and apoptosis in both SKOV-3 and OVCAR-3 cells. In addition, DIM treatment drastically reduced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK), which are downstream to EGFR, without affecting their protein levels. DIM treatment also inhibited the kinase activity of ERK, as observed by the down-regulation of phospho-E twenty-six like transcription factor 1 (p-ELK1) in all three ovarian cancer cell lines. DIM significantly suppressed the growth of ovarian tumors in vivo. Tumor growth suppressive effects of DIM in SKOV-3 tumor xenografts were associated with reduced phosphorylation of EGFR, MEK, and ERK. These results indicate that DIM induces apoptosis in ovarian cancer cells by inhibiting the EGFR-ERK pathway in vitro and in vivo.
... During cooking of cruciferous vegetables, the levels of ABG can decrease. When boiled for 10 min, the amount of ABG in cabbage is reduced by 10% ( Ciska et al., 2009). This degradation appears to be due to elimination of the ascorbyl moiety, as deduced by the simultaneous increase of ABG degradation products such as indole-3-carbinol. ...
While ascorbic acid (vitamin C) is mostly known as a cofactor for proline hydroxylase and as a biological antioxidant, it also forms covalent bonds with natural products which we here refer to as 'ascorbylation'. A number of natural products containing an ascorbate moiety has been isolated and characterized from a variety of biological sources, ranging from marine algae to flowering plants. Most of these compounds are formed either as a result of nucleophilic substitution or addition by ascorbate, e.g. the ascorbigens from Brassica species are ascorbylated indole derivatives. Some ascorbylated tannins appear to be formed from electrophilic addition to dehydroascorbic acid. There are also examples of annulations of ascorbate with dietary polyphenols, e.g. epigallocatechin gallate (EGCG) and resveratrol derivatives. Herein is a survey of 33 ascorbylated natural products and their reported biological activities.
Chemotherapy with doxorubicin (Dox) can lead to cardiotoxic effects, presenting a major complication in cancer therapy. Diindolylmethane (DIM), derived from cruciferous vegetables like cabbage, exhibits numerous health benefits. However, its clinical application is limited because of low bioavailability and suboptimal natural concentrations in dietary sources. To address this limitation, we developed a processing methodology, specifically fermentation and boiling, to enhance DIM levels in cabbage. High-performance liquid chromatography (HPLC) analysis revealed a threefold DIM increase in fermented cabbage and a substantial ninefold increase in fermented-boiled cabbage compared to raw cabbage. To evaluate the clinical implications, we formulated a DIM-enriched diet and administered it to mice undergoing Dox treatment. Our in vivo results revealed that Dox treatment led to cardiotoxicity, manifested by changes in body and heart weight, increased mortality, and severe myocardial tissue degeneration. Dietary administration of the DIM-enriched diet enhanced antioxidant defenses and inhibited apoptosis in the cardiac tissue by interfering with mitoptosis and increasing antioxidant enzyme expression. Interestingly, we found that the DIM-enriched diet inhibited the nuclear translocation of NF-kB in cardiac tissue, thereby downregulating the expression of inflammatory mediators such as TNF-α and IL-6. Further, the DIM-enriched diet significantly reduced serum cardiac injury markers elevated by Dox treatment. These results suggest that the DIM-enriched cabbage diet can serve as a complementary dietary intervention for cancer patients undergoing chemotherapy. Further, our research highlights the role of plant-based diets in reducing treatment side effects and improving the quality of life for cancer patients.
Indole-3-carbinol (I3C) is a bioactive phytochemical abundant in cruciferous vegetables. One of its main in vivo metabolites is 3,3'-diindolylmethane (DIM), formed by the condensation of two molecules of I3C. Both I3C and DIM alter multiple signaling pathways and related molecules controlling diverse cellular events, including oxidation, inflammation, proliferation, differentiation, apoptosis, angiogenesis, and immunity. There is a growing body of evidence from both in vitro and in vivo models that these compounds possess strong potential to prevent several forms of chronic disease such as inflammation, obesity, diabetes, cardiovascular disease, cancer, hypertension, neurodegenerative diseases, and osteoporosis. This article reviews current knowledge of the occurrence of I3C in nature and foods, along with the beneficial effects of I3C and DIM concerning prevention and treatment of human chronic diseases, focusing on preclinical studies and their mechanisms of action at cellular and molecular levels.
Tumor angiogenesis is primarily regulated by vascular endothelial growth factor and its receptor (VEGF-VEGFR) communication, which is involved in cancer cell growth, progression, and metastasis. Diindolylmethane (DIM), a dietary bioactive from cruciferous vegetables, has been extensively studied in preclinical models for breast cancer prevention and treatment. Nevertheless, the possible role of DIM in the angiogenesis and metastasis regulations in triple-negative breast cancer (TNBC) remains elusive. Here, we investigated the potential anti-angiogenic and anti-metastatic role of DIM in combination with centchroman (CC). We observed that the oral administration of the DIM and CC combination suppressed primary tumor growth and tumor-associated vascularization in 4T1 tumors. Further, the DIM and CC combination exhibited a strong inhibitory effect on VEGF-induced angiogenesis in matrigel plugs. The mechanistic study demonstrated that DIM and CC could effectively downregulate VEGFA expression in tumor tissue and strongly interact with VEGFR2 to block its kinase activity. Interestingly, the DIM and CC combination also suppressed the lung metastasis of the highly metastatic 4T1 tumors through the downregulation of FAK/MMP9/2 signaling and reversal of epithelial-to-mesenchymal transition (EMT). Overall, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating TNBC.
Sauerkraut juice has not gained much scientific attention to date. Therefore, this study aimed to track changes in glucosinolates (GLS) during fermentation of white cabbage and the formation of corresponding breakdown products in sauerkraut and sauerkraut juice separately and to evaluate their stability during prolonged storage of the final products.
The results obtained indicate that both sauerkraut and sauerkraut juice are a good source of bioactive compounds: ascorbigen and isothiocyanates. The stability of individual compounds during storage varied, and the absolute content of phytochemicals depended on the content of native GLS in the raw material and its bacterial composition. The dominant compound was ascorbigen, stable in acidic pH in both sauerkraut and sauerkraut juice, even after prolonged storage. Sauerkraut juice was also found as a rich source of bioactive isothiocyanates. One 250 mL glass of sauerkraut juice (after two weeks) can deliver approx. 75 μmol of bioactive ascorbien and isothiocyanates, hence it can be considered as functional food, delivering beneficial health effects.
Lactic acid (LA) fermentation of plant-based products is a commonly used process all over the world. Recently, except for extending the shelf-life of food and improving its palatability, the popularity of fermented food increased because of their nutritional and health-promoting quality. In this review, the existing knowledge about the effects of LA fermentation in different types of plant-based food matrices on their nutritive and health-promoting potential is presented and discussed based on the most recent studies. Furthermore, the toxicological and unfavorable effects are addressed.
This review shows that although the biotransformation of several nutrients and bioactive compounds and the strain-dependent properties need more in-depth elucidation in several matrices, the recently published studies proved that LA-fermented cereals, fruits, vegetables, legumes, and seaweeds are good sources of health-promoting molecules. The obtained products offer a good alternative for a growing number of vegans, vegetarians, and flexitarians, who look for the plant-based, healthy alternatives. However, still more clinical trials evaluating the effect of their consumption on the human health are in demand.
Cancer metastasis is a multistage phenomenon, which can be prevented by the administration of various phytochemicals. Phytochemicals inhibit or prevent cancer initiation, promotion, progression, as well as metastasis by employing antioxidant, anti-inflammatory effects mediated via NF-kκB, Nrf2, and AP-1 signaling. Besides, phytochemicals also mediate apoptosis in tumor cells and inhibition of cancer growth. The dietary phytochemicals are abundant in fruits and vegetables that appear to be consisting of beneficial effects against cancer metastasis and induce apoptosis and arrest cell growth by multiple mechanisms.
Gastrointestinal (GI) cancer is one of the lethal among all cancers which includes different types of cancers of the GI system, i.e., esophagus, liver, gallbladder, small intestine, pancreas, stomach, and bowel (large intestine or colon and rectum). Therefore, several efforts are being made to find more suitable anticancer agents based on synthetic and phytochemical approaches. There is the number of phytochemicals reported with prominent anticancer activities, but they include the number of limitations such as poor bioavailability, pitiable water solubility and low penetration into cells, contracted therapeutic index, and higher hepatic disposition. Therefore, this chapter discusses and summarizes the contemporary advances that have been made for the management of GI cancers in the field of nanotechnology with a combination of phytochemicals.
Introduction:
Brassica vegetables contain high levels of indole compounds which have been found to provide health benefits, especially as cancer-preventive agents. An efficient and rapid method using solvent extraction with capillary electrophoresis (CE) and ultraviolet (UV) detection was developed for the determination of four major indoles from four types of Brassica vegetables.
Materials and methods:
Freeze-dried samples of four Brassica vegetables, i.e. broccoli, cauliflower, Chinese cabbage and cabbage, were selected. Hence, 1 mL of the binary solvent dimethylformamide (DMF)-methanol, 4:1 (v/v), was used for sample extraction. The extracts were diluted with the running buffer and directly analysed using CE with UV detection of four indole compounds.
Results:
The binary solvent DMF-methanol, 4:1 (v/v) was selected from studies of the extraction efficiency of standard indoles spiked in ivy gourd (as the negative control sample) and using diphenylamine as the internal standard. Recovery was 80(±10)-120(±3)% for the four indoles: indole-3-carbinol (I3C), indole-3-acetonitrile (I3A), indole-3-acetic acid (IAA), and 3,3'-diindolylmethane (DIM). For direct analysis suitable dilution of the extract with the running buffer was required. The linear range of the quantitation is 0.75-25.0 μg/mL, limit of detection (LOD) of 0.14-0.52 μg/mL and r2 > 0.998. The amount of indole in the Brassica vegetables are in the order I3C > > IAA, I3A > DIM.
Conclusion:
A rapid method for extraction and quantitation of four indoles in four Brassica vegetables using CE with UV detection was developed. It has the potential as an efficient technique for generating data for use in agricultural and nutritional studies.
Background:
Kales are often a key ingredient of traditional foods, containing high amount of indolic glucosinolates (precursors of indole-3-carbinol and ascorbigen), carotenoids and phenolics. The present trend to associate traditional foods crops with health promoting properties, suggested to investigate the degradation kinetic of three Brassica oleracea landraces' phytochemicals, subjected to boiling, steaming and stir frying.
Results:
Boiling determined substantial losses, due to leaching. Glucosinolates followed a second order degradation kinetic (20% of their initial values after 10 minutes in Nero di Toscana). Phenolic content in leaves + cooking water remained unchanged, whereas however, their antioxidant capacity was reduced. Carotenoid content increased during the first minutes of boiling. Steaming showed the highest retention of phytochemicals, with often zero order degradation kinetic, having however a strong effect on colour. Stir frying produced high losses for all measured compounds; also β-carotene reduced its content to 10-23%, independently on variety. Conversion values for indole-derived compounds ranged from non-detectable to 23.5%.
Conclusion:
Variety strongly affected observed degradation rates, because of a different glucosinolate composition and leaf structure. With this research more information are gained on the kinetic degradation of Brassica oleracea landraces' phytochemical compounds upon cooking, highlighting the possibility of improving bioactive component retention.
A simple micellar electrokinetic chromatography (MEKC) method with UV detection was developed for the simultaneous determination of indole-3-carbinol, indole-3-acetonitrile, indole-3-acetic acid and 3,3′-diindolylmethane. These compounds are potentially used in cancer prevention. Investigation of solvent effects (methanol and dimethylformamide) on MEKC analysis was carried out. A dilute and shoot strategy was used for sample preparation to reduce the time required for multiple steps such as solvent evaporation. The final conditions were electrokinetic injection for 3.0 s at 423 V cm−1 and 20.0 mM borate buffer (pH 9.00) containing 20.0 mM SDS. Analysis was rapid, achieved in less than 4.5 min. Linear calibration curves for the indole compounds in the range 5–200 μg mL−1 (r2 > 0.999) were obtained. Intra- and inter-day precisions were 2.0–7.9% RSD, with LOQs in the range of 1.5–4.0 μg mL−1 and recoveries in the range of 90–110% (n = 5).
Objective: To investigate the effects of 3, 3'-diindolymethane (DIM) on the migration and invasion abilities of human ovarian cancer A2780 cells, and to explore the role of signal transducer and activator of transcription 3 (STAT3) pathway in the possible mechanism. Methods: The human ovarian cancer A2780 cells were treated with different concentrations of DIM. The adhesion, migration and invasion abilities of A2780 cells were determined by adhesion assay, wound healing assay, and Transwell chamber invasion assay, respectively. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in A2780 cells were observed under a laser scanning confocal microscope. The expression levels of STAT3, phospho-STAT3 (p-STAT3), VEGF and MMP-2 proteins were detected by Western blotting. Results: The adhesion ability of A2780 cells treated with DIM was inhibited in a dose-dependent manner. Wound healing assay showed that the rate of wound closure was significantly reduced in DIM-treated A2780 cells in a time- and dose-dependent manner (P < 0.05). The invasion assay showed that the numbers of A2780 cells treated with 50 and 100 μmol/L DIM invading through the chamber were both lower than that of the control cells [(326.00 ± 20.15)/field and (59.33 ± 13.32)/field vs (537.33 ± 53.15)/field, both P < 0.01]. Western blotting analysis demonstrated that the expressions of total STAT3 proteins had no significant change, but the expression levels of p-STAT3, VEGF and MMP-2 were down-regulated in A2780 cells treated with DIM (all P < 0.05). Under the laser scanning confocal microscope, the down-regulation of the expression levels of VEGF and MMP-2 in A2780 cells indued by DIM was observed. Conclusion: DIM can inhibit the invasion and migration abilities of ovarian cancer cells through down-regulation of p-STAT3, VEGF and MMP-2 proteins.
The influence of thermal treatment, pickling and fermentation on the content of glucobrassicin and its selected breakdown products in broccoli and cauliflower was investigated. The highest content of glucobrassicin and the lowest content of its breakdown products were found in vegetables which underwent thermal treatment such as boiling and steam cooking. The lowest content of glucobrassicin and the highest content of its breakdown products were present in raw, pickled and fermented vegetables in which the myrosinase remained active. Ascrobigen was the major glucobrassicin breakdown product and its content was negatively correlated with glucobrassicin content in broccoli and cauliflower. After heating of vegetables in 60 °C for 20 min (causing thermal deactivation of epithiospecific protein) no presence of indole-3-acetonitrile was found.
Base-switched methylenation and formylation using tetramethylethylenediamine (TMEDA) as a carbon source have been achieved under mild conditions, catalyzed by CuCl(2), with atmospheric oxygen as oxidant. Bisindolylmethanes, diphenylmethanes and 3-formylindoles were synthesized with excellent regioselectivity and good yield.
The aim of the study was to investigate the effect of the pasteurization process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. Pasteurization was run at a temperature of 80 °C for 5-30 min. Significant changes were only observed in contents of ascorbigen and 3,3'-diindolylmethane. The total content of the compounds analyzed in cabbage pasteurized for 10-30 min was found to be decreased by ca. 20%, and the losses were due to thermal degradation of the predominating ascorbigen. Pasteurization was found not to exert any considerable effect on contents of indole-3-acetonitrile and indole-3-carbinol in cabbage nor did it affect contents of the compounds analyzed in juice.
The effect of water- and steam-cooking on the content of vitamin C, polyphenols, carotenoids, tocopherols and glucosinolates, as well as on the antioxidant activity of broccoli, are reported. Flavonoids, phenolic acids, vitamins C and E, beta-carotene, lutein, and glucosinolates in domestically processed broccoli were quantified using high-performance liquid chromatography (HPLC) methods; total polyphenols were determined with Folin-Ciocalteu reagent. The antioxidant capacities of broccoli extracts were evaluated using the Trolox equivalent antioxidant capacity (TEAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. The results indicated that steam-cooking of broccoli results in an increase in polyphenols, as well as the main glucosinolates and their total content as compared with fresh broccoli, whereas cooking in water has the opposite effect. Steam-cooking of broccoli has no influence on vitamin C, whereas cooking in water significantly lowers its content. Both, water- and steam-cooking of broccoli results in an increase in beta-carotene, lutein, and alpha- and gamma-tocopherols as compared with fresh broccoli. Similar effects of steaming and water-cooking of broccoli on their antioxidant activity were observed.
Glucosinolates were evaluated in 5 groups and 65 accessions of Brassica oleracea (50 broccoli, 4 Brussels sprouts, 6 cabbage, 3 cauliflower, and 2 kale) grown under uniform cultural conditions. Glucosinolates and their concentrations varied among the different groups and within each group. The predominant glucosinolates in broccoli were 4-methylsulfinylbutyl glucosinolate (glucoraphanin), 3-butenyl glucosinolate (gluconapin), and 3-indolylmethyl glucosinoate (glucobrassicin). Glucoraphanin concentration in broccoli ranged from 0.8 mu mol g(-1) DW in EV6-1 to 21.7 mu mol g(-1) DW in Brigadier. Concentrations of the other glucosinolates in broccoli varied similarly over a wide range. In Brussels sprouts, cabbage, cauliflower, and kale, the predominant glucosinolates were sinigrin (8.9, 7.8, 9.3, and 10.4 mu mol g(-1) DW, respectively) and glucobrassicin (3.2, 0.9, 1.3, and 1.2 mu mol g(-1) DW, respectively). Brussels sprouts also had significant amounts of gluconapin (6.9 mu mol g(-1) DW). Wide variations in glucosinolate content among genotypes suggest differences in their health-promoting properties and the opportunity for enhancement of their levels through genetic manipulation.
The enzymatic, chemical, and thermal breakdown pathways of glucobrassicin, the major indolylmethyl glucosinolate of cruciferous vegetables, have been studied using synthetic 3H-labeled glucobrassicin (GBS). Radio-HPLC was used to analyze qualitatively and quantitatively the resulting products as well as their kinetics of formation. Enzymatic breakdown of GBS under myrosinase action gave rise to different indole compounds [indole-3-carbinol (I3C), indole-3-acetonitrile (IAN), and 3,3‘-diindolylmethane (DIM)]. At neutral pH, GBS degradation was almost complete after 1 h, and the major breakdown product was I3C, which could be converted to DIM. The formation of this self-condensation product was observed as photosensitive. In acidic conditions, enzymatic degradation of GBS was a slower phenomenon, requiring 24 h to be nearly complete. IAN and I3C were the only two products occurring, and it was observed that the light had no effect either on the rate of formation or on the relative proportions of the breakdown products observed. GBS appeared as a very stable compound since no chemical degradation could be observed after 2 h in different aqueous media with pH in the 2−11 range. Moreover, after exposure to heat treatment, GBS was weakly degraded (10% in 1 h), giving rise to a new minor indole condensation product corresponding to a 3-(indolylmethyl)glucobrassicin (IM-GBS). Keywords: Glucosinolates; glucobrassicin; indole derivatives; anticarcinogenic substances; enzymatic breakdown; chemical breakdown; thermal breakdown
The thermal decomposition of indole glucosinolates that occurs during cooking procedures and the autolysis of indole glucosinolates in raw Brassica vegetables were studied to evaluate the reported anticarcinogenic properties of these vegetables. Intact indole glucosinolates and the indole glucosinolate breakdown products, thiocyanate ion and indoleacetonitriles, were followed in raw (autolyzed), steamed (10 min), and cooked (40 min) samples of cabbage, cauliflower, broccoli, and Brussels sprouts. Heat treatment resulted in substantial decomposition of indole glucosinolates with thiocyanate ion and indoleacetonitriles accounting for 50 and 30%, respectively, of the degraded indoles. Autolysis, in contrast, resulted in the production of little or no indoleacetonitriles but with considerable production of thiocyanate ion and related compounds (i.e., indolemethanols). The consumption by humans of raw or variously cooked Brassica vegetables may result in different intakes of indole glucosinolate derived products, which ultimately could influence the anticarcinogenic properties of the vegetables.
Bei der Bildung des Ascorbigens aus L-Ascorbinsure und 3-Hydroxymethylindol tritt eine C-Alkylierung am C-2 des Ascorbat-Ions ein, wobei sich 2 diastereomere Ascorbigene bilden.
The concentrations of individual and total glucosinolates were measured in four types of Portuguese cabbage and in one hybrid white cabbage before and after cooking. Typical Portuguese culinary procedures include boiling the cabbage for 10 min but for particular kale types the leaves are first shredded then boiled for 5 min (Caldo verde). Analysis of the fresh cabbage, cooked leaves and cooking water showed that the glucosinolate content of the cabbages is reduced by more than 50%. Almost all of this loss is accounted for as intact glucosinolates in the cooking water, normally used for soups in Portugal.
Glucosinolates from seventy-nine 8-week-old plant species were hydrolysed and the volatile products identified by GC-MS and related to previous published findings. Known compounds, identified in new plant sources, were 4-methylthiobutyl thiocyanate in Alyssum, 4-methylthiobutyl isothiocyanate in Diplotaxis and Eruca and isopropyl isothiocyanate and 5-vinyl-2-oxazolidinethione in Plantago.
The effect of processing of vegetables on ascorbigen formation, the ultimate fate of its transformation, their pharmacological evaluation are areas requiring detailed study using analytical methods capable of measuring various individual components. A reversed-phase chromatographic system for separation of ascorbigen, which is an indole containing a derivative of l-ascorbic acid, and its synthetic analogs with different substituents in the indole nucleus was developed. The isocratic chromatographic system was also developed for separation of ascorbigen and its transformation products in acidic media. Ascorbigen B which was previously described as the 2-epimer of natural ascorbigen was shown by HPLC to be a mixture of compounds, where natural ascorbigen ‘dimer’ was the major component, and natural ascorbigen and its ‘trimer’ were the minor components. To determine the content of ascorbigen and its transformation products in extracts of fresh or sour cabbage a reversed-phase chromatographic system with gradient elution was developed, with l′-methylascorbigen as an internal standard. Extracts of fresh or sour cabbage contained the ascorbigen (2·4–5·5 mg per 100 g fresh weight), as the major component and ascorbigen ‘dimer’ (0·1–0·3 mg per 100 g fresh weight), ascorbigen ‘trimer’ (0·1–0·3 mg per 100 g fresh weight), 3-hydroxymethylindole (0·2–0·3 mg per 100 g fresh weight) and (indole-3-yl)acetonitrile (0·1–0·5 mg per 100 g fresh weight) as the minor components.
To evaluate individual variations in broccoli VOLTA F1 plants, the bioactive components of 15 florets that were cultivated
in identical agricultural and climatic conditions were analyzed. Glucosinolates were analyzed by HPLC; total phenolic compounds,
ascorbic and dehydroascorbic acids (vitamin C) and the DPPH• and OH• radical-scavenging activities of samples were also determined. Florets were characterized by particularly high glucoraphanin
content, 17.95μmol/g dry weight on average, which comprised about 50% of total glucosinolates. High individual variation
was observed for several bioactive compounds, as well as for DPPH• and OH• radical-scavenging activity. Coefficients of variability (CVs) were high, and except for one case, exceeded 10%. Among glucosinolates,
the highest CVs were noted for progoitrin (34.22%), 4-hydroxyglucobrassicin (27.32%) and neoglucobrassicin (24.44%). High
CVs were also observed for vitamin C (29.11%), including dehydroascorbic acid (26.72%), and for OH• (25.76%) and DPPH• (21.77%) radical-scavenging activities. Smaller variations were found for glucoraphanin (CV=14.84%) and polyphenols (CV=14.95%).
The effect of different cooking times on the GLS content in white cabbage (Brassica oleracea L. var. capitata f. alba) was determined. Cooking of cabbage for 5-30 min caused a gradual decrease in the GLS content. The most efficient reduction of the GLS content (by about 35%) occurred during the first minutes of cooking. As the cooking time was extended by another 5 min, each time the GLS content decreased by 10-15%. Higher losses in indole GLS, as compared to those of aliphatic ones, resulted from more efficient diffusion of those compounds to cooking water. The GLS content in cooking water, irrespective of the cooking time of white cabbage, remained rather stable, whereas the content of indole GLS was between 3.5- and 4-fold higher in comparison to that of aliphatic GLS. Taking into consideration the rate of changes in the content of particular GLS in cabbage and the GLS content in cooking water, it can be stated that glucoiberin was more thermolabile than other GLS.
The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are usually broken down through hydrolysis catalyzed by myrosinase, an enzyme that is released from damaged plant cells. Some of the hydrolysis products, viz. indoles and isothiocyanates, are able to influence phase 1 and phase 2 biotransformation enzyme activities, thereby possibly influencing several processes related to chemical carcinogenesis, e.g. the metabolism, DNA-binding and mutagenic activity of promutagens. A reducing effect on tumor formation has been shown in rats and mice. The anticarcinogenic action of isothiocyanates and indoles depends upon many factors, such as the test system, the target tissue, the type of carcinogen challenge and the anticarcinogenic compound, their dosage, as well as the timing of the treatment. Most evidence concerning anticarcinogenic effects of glucosinolate hydrolysis products and brassica vegetables has come from studies in animals. Animal studies are invaluable in identifying and testing potential anticarcinogens. In addition, studies carried out in humans using high but still realistic human consumption levels of indoles and brassica vegetables have shown putative positive effects on health.
The contents of glucosinolates in twenty-four cultivars of calabrese, green sprouting broccoli, have been determined using glucose release and high performance liquid chromatographic methods. The levels of total glucosinolates (range, 42·1–94·5 mg 100 g−1 fresh weight; mean, 62·3 mg 100 g−1 fresh weight) were comparable with those reported previously for cauliflower, but lower than those found in cabbage and, especially, Brussels sprouts. Analysis of the individual components revealed the main species to be 4-methylsulphinylbutyl glucosinolate (glucoraphanin) and, particularly, glucobrassicin and neoglucobrassicin, containing 3-indolylmethyl and 1-methoxy-3-indolylmethyl side chains, respectively. The individual glucosinolate contents of calabrese and cauliflower are compared and differences are considered in the context of biosynthetic pathways. The consequences of these findings for the flavour and biological properties of calabrese are briefly discussed.
Synthesized glucobrassicin, an indole glucosinolate present in rape, was submitted to exogenous enzymatic degradation with commercial myrosinase at two different pH values. Organic products were analysed after silylation by gas chromatography using a thermoionic detector. Three products (3-indolemethanol, 3-indoleacetonitrile and 3,3′-diindolylmethane) were identified by comparison with the retention times of silylated authentic materials and by gas chromatography-mass spectrometry. Two different degradation schemes were proposed according to the pH conditions: 3-indoleacetonitrile was obtained at acidic pH and 3,3′-diindolylmethane at neutral pH. The synthetic glucobrassicin thus behaved in the same manner as the natural product.
Thermal degradation of individual glucosinolates within the plant matrix was studied. Red cabbage samples were heated at different temperatures for various times. To rule out the influence of enzymatic breakdown and to focus entirely on the thermal degradation of glucosinolates, myrosinase was inactivated prior to the thermal treatments. All identified glucosinolates degradation when heated at temperatures above 100 °C. The indole glucosinolates 4-hydroxy-glucobrassicin and 4-methoxyglucobrassicin showed the highest degree of showed degradation, even at temperatures below 100 °C.Kinetic parameters have been estimated for the degradation that could be described by first-order kinetics. At temperatures below 110 °C indole glucosinolates have a significant higher degradation rate constant as compared to aliphatic glucosinolates. The breakdown of 4-hydroxyglucobrassicin seems to consist of two parallel reaction pathways. Based on the proposed degradation kinetics and the estimated parameters, the degree of thermal degradation of all individual glucosinolates at standardized heating conditions (blanching, cooking and canning) was simulated. Glucosinolates are expected to be not very susceptible to thermal degradation during blanching conditions. Cooking will cause more thermal degradation to indole glucosinolates (38%) as compared to aliphatic glucosinolates (8%). Canning, the most severe heat treatment, will result in significant thermal degradation (73%) of the total amount of glucosinolates.
Brassica vegetables contain high amounts of glucosinolates, which contribute to the beneficial health effects of their consumption. Processing of such vegetables in domestic food preparation or industrial processing will influence levels of glucosinolates considerably and thus affect their health‐protective capacity. This study demonstrates the effects of chopping of raw Brassica vegetables on their glucosinolate composition. Limited breakdown of aliphatic glucosinolates in cabbage was found, whereas unexpected increased levels of indolyl glucosinolates were detected after chopping and storage of cabbage and broccoli under ambient conditions. In chopped white cabbage a 15‐fold increase of 4‐methoxy‐ and 1‐methoxy‐3‐indolylmethyl glucosinolates was noted after 48 h of storage. Chopping and storage of broccoli resulted in a strong reduction of most glucosinolates, except for 4‐hydroxy‐ and 4‐methoxy‐3‐indolylmethyl glucosinolates, which increased 3.5‐ and 2‐fold respectively. The myrosinase‐mediated hydrolysis of glucosinolates appears to be counteracted by a post‐harvest increase of some indolyl glucosinolates. In this paper we propose a mechanism of stress‐induced increase of glucosinolates, which plays an important role besides the well‐known breakdown mechanism.
© 2001 Society of Chemical Industry
Indole-3-carbinol [I3C, also called 3-(hydroxymethyl)indole] is a naturally occurring modulator of carcinogenesis with a biological activity that is at least partially dependent on its conversion to active substances in acidic media. We compared the identities of the major oligomeric products of I3C produced under conditions approximating those found in gastric juice with the reported identities of products of 3-substituted indoles produced under enzymatic and other nonenzymatic conditions. After a 10-min treatment in aqueous HCl solution, I3C was converted in 18% yield to a mixture of acetonitrile-soluble products, the major components of which (as determined by HPLC) were diindol-3-ylmethane (5.9%), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le (2.0%), and [2-(indol-3-ylmethyl)indol-3-yl]indol-3-ylmethane (5.9%). Tentative assignments were made for 3,3-bis(indol-3-ylmethyl)indolenine (0.59%), a symmetrical cyclic tetramer (0.64%), and a linear tetramer (1.1%). Indolo[3,2-b]carbazole (ICZ) was formed slowly in aqueous acidic solutions in low yields (2.0 ppm) which increased to greater than 90 ppm following addition of an organic solvent [tetrahydrofuran (THF) or dimethylformamide (DMF)] to a neutralized solution. Relative yields of trimers vs dimer increased with decreasing pH and with decreasing starting concentration of I3C. Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes. A mechanistic rationale is presented for the formation of the identified products.
The potency of indole-3-carbinol (I3C) to form condensation products under acidic aqueous conditions was studied. After identifying a known dimer, 3,3'-diindolylmethane (DIM), we elucidated the structures of two trimers also found in acid reaction mixtures: 5,6,11,12,17,18-hexahydrocyclonona[1,2-b:4,5-b':7,8-b"]tri-indole (CTI), and 2,3-bis[3-indolylmethyl] indole (BII). The formation of these indole oligomers was shown to be pH dependent. The highest amounts of DIM and BII were formed in aqueous solutions having a pH value ranging from 4 to 5. No CTI could be detected at pH values above 4.5. In rats that received an oral dose of I3C we could detect DIM and BII in gastric contents, stomach tissue, small intestine and liver. No CTI could be detected in vivo after oral exposure to I3C. In in vitro experiments, using rat hepatocytes, the cytochrome P-450IA1 apoprotein level, 7-ethoxyresorufin O-deethylation activity (EROD) and DT-diaphorase activity (DTD) were markedly enhanced by DIM and CTI as well as BII.
Three varieties of cabbage, Roundup, Sanibel, and TBR Globe, were commercially processed into sauerkraut. The aglucon products from two of the three glucosinolates abundant in kraut cabbage were measured at intervals from fresh cabbage to canning of the sauerkraut. Within the first 2 weeks of fermentation, all the glucosinolates were hydrolyzed. Thiocyanate ion and 1-cyano-3-methylsulfinylpropane, the aglucon products measured, varied little from 2 weeks of fermentation to finished sauerkraut. In the finished kraut, thiocyanate ion ranged from 9 to 17 ppm and 1-cyano-3-methylsulfinylpropane ranged from 16 to 25 ppm. No isothiocyanates or goitrin were present. No nitriles from allyl glucosinolate were found.
In the present study analytical and preparative supercritical fluid chromatography (SFC) were used for investigation of myrosinase catalysed degradation of 4-hydroxybenzylglucosinolate (sinalbin). Sinalbin occurs as a major glucosinolate in seeds of Sinapis alba L., in various mustards and other food products. The degradation products were identified and quantified by analysis based on a developed SFC method using a bare silica column. Determinations comprised transformation products of sinalbin, produced both during degradation of isolated sinalbin, and during autolysis of meal from S. alba seeds. The conditions in the developed SFC method were used as basis for the preparative SFC procedure applied for isolation of the components prior to their identification by nuclear magnetic resonance (NMR) spectroscopy. Myrosinase catalysed sinalbin hydrolysis resulted in the reactive 4-hydroxybenzyl isothiocyanate as an initial product at pH values from 3.5 to 7.5 whereas 4-hydroxybenzyl cyanide was one of the major products at low pH values. 4-Hydroxybenzyl isothiocyanate was found to disappear from the aqueous reaction mixtures in a few hours, as it reacted easily with available nucleophilic reagents. 4-Hydroxybenzyl alcohol was found as the product from reaction with water, and with ascorbic acid, 4-hydroxybenzylascorbigen was produced.
Individual glucosinolates (GLS) were determined in vegetables of three Cruciferae species: Brassica oleracea L. (white cabbage, red cabbage, Savoy cabbage, Brussels sprouts, cauliflower, kale, kohlrabi), Brassica rapa L. (turnip), and Raphanus sativus L. (red radish, black radish, and white radish) produced in two years. The cultivars were compared for the contents of total-, indole-, and aliphatic GLS. In both years, the total content of GLS was highest in black radish, and all examined R. sativus vegetables contained the greatest amount of aliphatic GLS. Neither the level nor the identity of GLS differentiated among the vegetables of the other cultivars grown in the same year. Comparison of the GLS contents of the same cultivar in two production years, which differed in temperature and rainfall rate, showed that low average 10-day rainfall and high average temperature during the vegetation period significantly increased the GLS content of vegetables. This suggests that the year x cultivar interaction modified the GLS content of vegetables.
Several epidemiologic studies suggest that consumption of cruciferous vegetables may be particularly effective (compared with total fruit and vegetable consumption) in reducing cancer risk at several organ sites. Crucifers that are widely consumed are especially rich in glucosinolates, which are converted by plant myrosinase and gastrointestinal microflora to isothiocyanates. A number of isothiocyanates and a limited number of glucosinolates that were examined effectively block chemical carcinogenesis in animal models. Many isothiocyanates are also potent inducers of phase 2 proteins. Substantial evidence supports the view that phase 2 enzyme induction is a highly effective strategy for reducing susceptibility to carcinogens. This conclusion has recently received strong molecular support from experiments on mice in which the specific transcription factor, nrf2, which is essential for induction of phase 2 proteins, was deleted. In these knock-out mice, the basal levels of phase 2 enzymes are very low and not inducible. Accordingly, these mice are much more susceptible than their wild-type counterparts to benzo[a]pyrene forestomach carcinogenesis and are not protected by phase 2 inducers. These experiments provide very strong evidence for a major role of phase 2 enzymes in controlling the risk of exposure to carcinogens. An increasing number of phase 2 proteins that exert a variety of protective mechanisms are being identified. Thus, in addition to detoxifying electrophiles, these proteins exercise versatile, long-lasting and catalytic antioxidant protection.
A high-performance liquid chromatographic method was developed for the simultaneous determination of indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr(1)), and indolo[3,2b]carbazole (ICZ). Compounds were extracted from mouse plasma using tert.-butyl methyl ether, incorporating 4-methoxy-indole as internal standard. Chromatographic separation utilized a Waters Symmetry RP18 in tandem with a Thermoquest BDS C(18) column, an acetonitrile-water gradient and UV (280 nm) in series with fluorescence (ex. 335 nm; em. 415 nm) detection. Calibration curves were linear (r(2)>0.99) between 50 and 15,000 ng/ml for I3C; 150 and 15,000 ng/ml for LTr(1); and 0.15 and 37.5 ng/ml for ICZ and the method was reproducible and precise (within-day and between-day coefficients of variation below 9.7 and 13%, respectively). The method described is suitable for comprehensive pharmacokinetic studies with indole-3-carbinol.
The formation of plant-derived biomolecules during sauerkraut fermentation was studied. Cabbage was fermented with a starter culture, and the results were compared to the results of spontaneous fermentation. The concentration of flavonoids and glucosinolates was analyzed by HPLC, and that of the glucosinolate breakdown products, by GC-MS. Of the 20 different flavonoids tested, only kaempferol was found (0.9 mg/ kg FW, fresh weight). The content of kaempferol remained constant in the cabbage fiber matrix over the fermentation process. The nitrite concentration was below the detection limit in both fermentations. The total glucosinolate content in the raw material was 3.71 micro mol/g DW, dry weight. Glucosinolates were totally decomposed in both fermentations during two weeks, and different types of breakdown products were formed. Isothiocyanates, indole-3-carbinol, goitrin, allyl cyanide, and nitriles were determined in the fermented cabbage. Isothiocyanates and allyl cyanide were the predominant breakdown products in both fermentations. Sulforaphane nitrile and goitrin were found only in small quantities in the end products.
Total and individual levels of glucosinolates (GSs) were measured in red cabbage after various microwave treatments varying in time and intensity of the treatments. Furthermore, the myrosinase enzyme activity of the microwave-heated vegetables was determined. The retention of GSs in the cabbage and the residual activity of the hydrolytic enzyme as a result of microwave preparation were compared with untreated cabbage. In general, high total GS levels were observed for all of the applied microwave treatments. Strikingly, many of the time/energy input combinations resulted in levels exceeding the total GS content of the untreated cabbage material. Moreover, the increase in levels seems to be associated with the energy input applied. A possible explanation for this behavior is an increased extractability of GS from heat-treated cabbage as compared to raw cabbage. Substantial myrosinase activity was retained in cabbage treated at low (24 min, 180 W) and intermediate microwave powers (8 min, 540 W) while microwave cooking for 4.8 min at 900 W (259.2 kJ energy input) resulted in a complete loss of hydrolytic activity. In this respect, differences in observed temperature profiles of the various microwave treatments play an important role. Higher retention of GSs and controllable amounts of active myrosinase can offer increasing health-promoting properties of microwave-prepared Brassica vegetables.
The research focused on the glucosinolate (GLS) breakdown products formed during the fermentation of cabbage. A relationship between the contents of degradation products in fermented cabbage and native GLS in raw cabbage was investigated. The effect of fermented cabbage storage on the contents of individual compounds was also assayed. Ascorbigen formed from one of the degradation products of glucobrassicin (indole GLS) was found to be a dominating compound in fermented cabbage. Irrespective of the time of fermented cabbage storage, the content of ascorbigen reached approximately 14 micromol/100 g. Neither the content of isothiocyanates, the major degradation products of aliphatic GLS, nor that of cyanides exceeded 2.5 microM. Storage of cabbage caused periodical increases and decreases in the contents of cyanides and consequent declines in the contents of isothiocyanates. The highest relative contents (expressed as a percentage of the native GLS content) of degradation products--ranging from >70 to 96%--were reported for the products of glucoraphanin degradation, whereas the lowest-- <5% --were reported for the products of sinigrin degradation.
Kapusta kwaszona PN-72, A77700
- Polska Norma
Polska Norma. Kapusta kwaszona PN-72, A77700.
- G Kiss
- H Neukom
- Ber Die
Kiss, G.; Neukom, H. Ü ber die Struktur des Ascorbigens. HelV.
Chim. Acta 1966, 49, 989-992.
This research has been carried out in part under the financial support from the State Committee for Scientific Research
- Polska Norma
Polska Norma. Kapusta kwaszona PN-72, A77700.
Received for review November 6, 2008. Revised manuscript received
February 3, 2009. Accepted February 5, 2009. This research has been
carried out in part under the financial support from the State
Committee for Scientific Research (2P06T 061 28/2005).