Aim. The aim of the study was to review the literature on the combination of cytostatics with flavonoids as a promising way to improve the cancer therapy. Material and methods. A review of Polish and foreign literature was performed. The following databases were searched: PubMed, Scopus, Science Direct, and Polish Medical Bibliography. Literature analysis. Effective strategies to inhibit the progression of cancer are needed. Compounds of natural origin, including plant polyphenols, are a part of our diet. Due to their availability, and antioxidant properties, they may serve as efficacious adjuvants in cancer therapy, enhancing the effectiveness of chemotherapeutics. Epidemiological studies have shown an inverse relationship between diets rich in fruits, vegetables, and supplements, and the risk of all causes of death from cancer. Based on their diverse biological activity, flavonoids may be potential adjuvant therapeutic agents that act synergistically with cytostatics for treatment of many types of cancer. This review of the results is a summary the research on anticancer activity of flavonoids and may also raise consciousness of consumers, who will be able to compose their diet armed with the knowledge of preventive and therapeutic anticancer properties of food ingredients. There is need for further research on polyphenols of plant origin, including interactions among food components that coexist. Another important aspect is to understand how the activity of phytocompounds depends on concentration and the presence of additional factors (e.g. microflore, metal ions), which could possibly make a compound harmful, instead of having positive theraputics effect. Elucidation of the mechanisms involved in biological activity of the described phytocompounds is essential for a better understanding of their influence on an organism.
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The aim of the studies was to establish relationships between flavonoids and elements important for human health. Therefore, total contents of flavonoids and phosphorus were determined by UV/Vis methods, flavonoids by HPLC, and Ca, Mg, Fe, Mn, Zn and Cu by FAAS in 68 infusions of medicinal herbs. Total flavonoids content in the aqueous extracts were in the range of 0.26 - 16.40 mg per 100 mL. The mean flavonoid contents (in mg per 100 mL of aqueous extract) were 2.24, 2.01, 1.83, 1.88 for rutin, myricetin, quercetin and kaempferol, respectively. The concentrations of Ca, Mg, P were determined in mg per 100 mL, and of Fe, Mn, Zn and Cu in μg per 100 mL. Total content of flavonoids was weakly correlated with quercetin (r = 0.41), kaempferol (r = 0.53), Cu (r = 0.43), and Ca (r = -0.30). Statistically significant correlations were also found among Cu, Ca, Mn, Zn and Fe. Cluster analysis grouped the studied herbs based on total flavonoids, also four flavonoids and essential elements contents, extracted from the whole population of herbs Sambuci flos, Betulae folium, and Sylibi mariani semen. Principal component analysis confirmed these findings and enabled identification of quercetin, kaempferol, Cu and Fe as the factors responsible for differentiation of the studied material.
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Epimedium pubescens Maxim. and Epimedium koreanum Nakai. are two common and confused species of Herba Epimedii in Chinese Pharmacopoeia 2010 edition. Different species and growing conditions lead to chemical differences between the two species which may result in the improper clinical usage. In this work, a new method based on rapid-resolution liquid chromatography combined with time-of-flight mass spectrometry (RRLC/TOFMS) has been developed for identification and differentiation of major flavonoids in two kinds of Epimedium extract and rat plasma. The compounds were identified effectively based on the accurate extract masses and formulae acquired by RRLC/TOFMS. The fragmentation rules deduced by collision-induced dissociation (CID) were successfully implemented in distinguishing some of the isomers, further validating the results. By using the combined analytical techniques, a total of 40 major flavonoids in extracts of two kinds of Epimedium were identified within 30 min, including 31 common components and 9 characteristic components. After oral administration, three prototype compounds in rat plasma were detected by comparing the constituents measured in vitro with those in vivo, and five metabolites were identified by contrasting the fragmentation rules. The identification and structural elucidation of the chemical constituents provided essential data for further pharmacological and clinical studies on different species of Epimedium.
From the flowers of Ficaria verna Huds. (Ranunculaceae), two flavonol triglycosides were isolated and their structures were elucidated by spectroscopic analysis (UV, NMR, MS) as 3-O-[_-L-rhamnopyranosyl-(1_6)-_-D-glucopyranosyl]-7-O-(_-D-glucopyranosyl) - quercetin (1) and 3-O-[_-L-rhamnopyranosyl-(1_6)-_-D-glucopyranosyl]-7- O-(_-D-glucopyranosyl) - kaempferol (2). In addition, the structure of 1 was determined using homo- and heteronuclear 2D NMR techniques.
Thymus serpyllum L. (T.serpyllum) has a great interest as a potential plant component, which is used in the production of fermented milk products with anticancer effect. The plant material was collected at the flowering stage. Chemical composition of essential oil and flavonoids from the aerial parts of the T. serpyllum, grown in the Southern Altai of the East Kazakhstan region, has been investigated for the first time. Output of the essential oil received from the aerial part of the plant in the flowering stage was on average 0,2%. Forty-one compounds were identified in T. serpyllum essential oil, which accounts for 96, 1% of the total oil. The main components of the oil were thymol (41,8%), γ-terpinene (15,3%), o-cymene (10,9%). Apart from the composition of essential oils, there were shown some flavonoids, such asapigenin 7 glucoside (0.24 % of dried plant material), luteolin (0,039 %), quercetin (0,006 %), which demonstrated a cytotoxic effect on cancer cells. In our experiments, luteolin had greater cytotoxic effect on cancer cells HCT-15 than quercetin. IC50 value of quercetin (100 μM) was higher than that of luteolin (50 μM).
The phytochemical investigation of the ethyl acetate soluble fraction of the whole plant of Pulicaria undulata L. (syn. Pulicaria crispa Forssk.) yielded two new flavonoid glycosides, pulicaroside (1) and undulatoside (6) along with four known flavonones (2-5). The structures of the new compounds were identified by 1D and 2D-NMR techniques along with other spectral evidences and by the comparison with the published data of the closely related compounds. All the flavonoids (1-6) exhibited superoxide anion scavenging activity.
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Phyllostachys edulis (PES), the most important bamboo species in China, is widely distributed in East Asia. Flavonoids, which are important bioactive natural compounds, often have similar structures, making their structural elucidation difficult. The aim of this study was to represent valuable, reliable mass spectral data for the identification of flavonoids in plant leaves. Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF-MS/MS) method was established for characterization and identification of the major flavonoids in PES leaf extract. A total of 13 flavonoids were simultaneously characterized, and their proposed characteristic product ions and fragmentation pathways were investigated. Thirteen compounds were separated on an Agilent Zorbax RRHD SB-C18 column (150 mm × 2.1 mm, 1.8 μm). On the basis of comparing with the 4 reference standards and the literature data, the other 9 flavonoids were identified by tandem mass spectrometry (MS/MS). Eight compounds (compounds 1, 4, 5, 8, 9, 10, 11, and 12) were found in PES leaves for the first time. An efficient UPLC–QTOF-MS/MS method was successfully applied for the structural identification of flavonoids in PES leaves. These results have practical applications for the rapid identification and structural characterization of these compounds in crude bioactive extracts or mixtures.
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The ferryl derivatives of hemoglobin are products of the reactions of oxy- and methemoglobin with hydrogen peroxide. Ferryl hemoglobins, either with or without a radical site on the protein moiety, are oxidizing species. Plant polyphenols, flavonoids, have been shown to act as antioxidants in vivo and in vitro. Reactions of met- and oxyhemoglobin with hydrogen peroxide in the presence of catechin, quercetin and rutin were studied. These flavonoids accelerated reduction of ferryl hemoglobin to methemoglobin. The rate constants of the reactions of ferryl hemoglobin with catechin, quercetin and rutin were in the order of 102 M-1 s-1, i.e. similar to the rate constants of ferryl hemoglobin with intracellular reducing compounds like urate or ascorbate. The beneficial effect of flavonoids against oxidative damage of hemoglobin caused by hydroperoxides, reported in the literature, is probably, at least in part, connected with the ability of flavonoids to scavenge ferryl hemoglobin.
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Scentless chamomile (Tripleurospermum inodorum = M. inodora) is a plant belonging to Anthemideae tribe of Asteraceae family, with phenotype similar to the common chamomile, a plant used in human consumption in the form of herbal tea infusion. In order to be able to understand possible health-promoting properties and adverse effects of the scentless chamomile's consumption, it is of essence to examine its chemical composition. The aim of the study was to perform phenolic profiling using high-performance liquid chromatography–tandem mass spectroscopy (HPLC–MS/MS), in comparison to the common chamomile. In the investigated extracts, qualitative and quantitative analyses enabled the identification of 66 compounds based on their retention times, mass (MS/MS) spectra, and analysis of their characteristic fragmentation patterns in MS/MS Product Ion Scan experiments. A new HPLC–MS/MS method for quantitation of common plant metabolites was hereby developed, enabling quantitation of 47 compounds. All examined M. inodora samples have relatively high combined phenolic and flavonoid contents (25.2–51.9 mg/g). Apigenin, apigenin-7-O-glucoside, luteolin, luteolin-7-O-glucoside, quinic acid, and 5-O-caffeoyl quinic acid were the compounds with highest concentration in both inodorous and common chamomile. The results obtained hereby represent the first and most detailed chemical profile of scentless chamomile so far.
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Flavonoids exhibit prooxidant cytotoxicity in mammalian cells due to the formation of free radicals and oxidation products possessing quinone or quinomethide structure. However, it is unclear how the cytotoxicity of flavonoids depends on the ease of their single-electron oxidation in aqueous medium, i.e., the redox potential of the phenoxyl radical/phenol couple. We verified the previously calculated redox potentials for several flavonoids according to their rates of reduction of cytochrome c and ferricyanide, and proposed experimentally-based values of redox potentials for myricetin, fisetin, morin, kaempferol, galangin, and naringenin. We found that the cytotoxicity of flavonoids (n=10) in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) and murine hepatoma (line MH-22a) increases with a decrease in their redox potential of the phenoxyl radical/phenol couple and an increase in their lipophilicity. Their cytotoxicity was decreased by antioxidants and inhibitors of cytochromes P-450, α-naphthoflavone and isoniazide, and increased by an inhibitor of catechol-O-methyltransferase, 3,5-dinitrocatechol. It shows that although the prooxidant action of flavonoids may be the main factor in their cytotoxicity, the hydroxylation and oxidative demethylation by cytochromes P-450 and O-methylation by catechol-O-methyltransferase can significantly modulate the cytotoxicity of the parent compounds.
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Flavonoids belong to a large group of natural compounds of substantial biological activity. Some examples are rutin and hesperidin which are widely used in medical treatment. Recent growing interest in these compounds comes of their possible application as natural antioxidant protecting against harmful action of free radicals. Moreover, flavonols could complex metal cations and some of them are used as analytical reagents [6-8]. The major reason for limited application of flavonoids is their weak solubility in water. Sulfonic derivatives of flavonoids due to the presence of sulfonic group in the molecule are well soluble in water. They form complexes with metal ions like their mother compounds and the complexation range is significantly wider than bioflavonoids. It in proposed to use quercetin-5'-sulfonic acid (QSA) (1) and sodium salt of morin-5'-sulfonic acid (NaMSA) (6) as new reagents in spectrophotometric determination of metals [18, 19]. Some of the compounds of Al, Ga and In with quercetin-5'-sulfonic acid and sodium salt of morin-5'-sulfonic acid show strong luminescence and for this reason can be used in laser technology. It has been found that sulfonic derivatives of quercetin could be an effective antidote against heavy metals - Hg(II), Cd, Pb(II) and as reported [37, 38] sodium salt of quercetin-5'-sulfonic acid (2) is a particularly active one. Sulfonic derivatives of quercetin, morin and chrysin, exhibit also the activity in different biological systems. It is supposed that sulfonic derivatives of flavonoids could have greater practical application than their mother compounds.
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Patrinia scabiosaefolia Fisch. (PSF), a well-known traditional Chinese medicine, has been demonstrated to show therapeutic effects on inflammatory bowel disease. In this study, a rapid and sensitive method using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was developed for identification of the major constituents in PSF. The separation analysis was performed on Waters Acquity UPLC system, and the accurate mass of molecules and their fragment ions were determined by Q-TOF-MS. Thirty-one constituents, including triterpenoids, iridoids, flavonoids, and organic acids were detected and tentatively deduced on the basis of their element compositions, tandem mass spectrometry (MS/MS) data, and relevant literatures. Twelve constituents were discovered for the first time in PSF. The results demonstrated that hederagenin-type and oleanolic acid-type saponins were the main constituents of PSF. Our work provides a certain foundation for further quantitation of major chemical constituents and in vivo pharmacokinetic studies of PSF. Moreover, the analytical approach developed herein has proven to be generally applicable for profiling the chemical constituents in traditional Chinese medicines (TCMs) and other complicated mixtures.
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A new method for the analysis of four target flavonoids in two kinds of citrus samples by ultra-high performance supercritical fluid chromatography (UHPSFC) method was developed. Main variables affecting the UHPSFC separation were optimized, and under the optimized conditions the four target compounds (tangeretin, nobiletin, hesperetin and naringenin) can be separated within 10 min. The UHPSFC method allowed the determination of the four target compounds in the diluted stock solutions with limit of detection (LOD) ranging from 1.08 to 2.28 μg mL⁻¹, and limit of quantification (LOQ) ranging from 1.45 to 4.52 μg mL⁻¹, respectively. The coefficients of determination (R2) of the calibration curves were higher than 0.9950. The recoveries of the four target compounds at three different concentrations were in the range of 82.4–117.6%. The validation results demonstrated that the proposed method is simple, accurate, time-saving and environment friendly, and it is applicable to a variety of complex samples such as medicine-food dual purpose herbs and functional foods.
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A high-performance liquid chromatographic (HPLC) technique coupled with photodiode array (PDA) detection has been proposed for simultaneous determination of five flavonoids, i.e. quercetin 3-O-β-D-glucopyranoside, quercetin 4′-methoxy-3-O-β-D-galactopyranoside, kaempferol 3-O-β-L-rhamnopyranoside, asebotin, and kaempferol 7-methxoy-3-O-α-L-rhamnopyranoside in extract of the whole plant of Saussurea mongolica Franch. The optimum conditions for separation were achieved on a 4.6 × 250 mm i.d., 5-μm particle, C18 column with acetonitrile and 1% acetic acid (20:80, v/v) as the mobile phase at a flow rate of 1.0 mL min−1. For all the analytes, a good linear regression relationship (r of >0.999) was obtained between peak area and concentration over a relatively wide range. The method was validated for repeatability, precision, stability, and accuracy. Seven different extraction procedures were investigated for preparation of the sample solution. The validated method was successfully applied to simultaneous analysis of these flavonoids in S. mongolica and was found to be simple and efficient.
SSixteen ethanolic extracts were obtained from seven different bee bread samples. The total flavonoid content in the extracts was determined by aluminium-chloride method and was in the range of 8.3 mg/L±6.24% to 195.3 mg/L±1.35% and 28.8 mg/L±19.33% to 603.3 mg/L±4.64% with reference to quercetin and rutin, respectively. The relative standard deviations (RSD) for parallel measurements for the calibration curves of quercetin dehydrate and rutin trihydrate were in the range of 0.51% to 9.39% and 5.02% to 19.91%, respectively. The RSD for parallel measurements for the extracts with reference to quercetin dihydrate and rutin trihydrate were in the range of 0.23% to 11.64% and 4.64% 19.33%, respectively. The total flavonoid content mainly depended on a ratio of bee bread to 50% ethanol and technology of obtaining bee bread. The significant differences between results were statistically confirmed. The best antibacterial activity of bee bread extracts was found against Bacillus cereus CCM 2010, Clostridium perfringens CCM 4435, and Staphylococcus aureus subsp. aureus CCM 4223. The activity of the bee bread extracts against Gram negative bacteria, Aspergillus and Penicillium genera was lower with moderate anticandidal activity. The obtained results indicated that it was very important to employ extracts with a high content of bee bread in 50% ethanol (1:5, 1:10). According to the results of this study, bee bread is a product which is rich in flavonoids and with good antibacterial activity against Gram positive bacteria and can be considered as a raw material for development of diet supplements and antimicrobial medicinal products
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Red amaranth (Amaranthus cruentus) and quinoa (Chenopodium quinoa ) are pseudocereals with particularly highly regarded nutritional value. Because of the high biological significance of the flavonoids and phenolic acids in these plants, qualitative and quantitative analysis has been performed by HPLC. Extracts from the seeds of two amaranth varieties (A. cruentus v. Rawa and v. Aztek) and quinoa seeds, and their sprouts grown in natural conditions and in the dark were analyzed. The main phenolic acid found both in seeds and sprouts was gallic acid. p -Hydroxybenzoic acid, vanillic acid, p -coumaric acid, caffeic acid, and cinnamic acid were also found in the seeds and p -coumaric acid, syringic acid, and ferulic acid in the sprouts. The main flavonoid found in the sprouts was rutin. Vitexin, isovitexin, and morin were also detected in the sprouts, and orientin, vitexin, isovitexin, morin, and traces of hesperidin and neohesperidin in the seeds. Although sprouting conditions (daylight or darkness) had no effect on gallic acid content, light caused an increase in the amount of rutin and darkness resulted in increased amounts of isovitexin and vitexin.
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Oxytropis falcata Bunge, known as the “king of herbs” in Tibetan medicine, is used for treatment of hyperpyrexia, pain, wounds, inflammation, and anthrax. However, it is difficult to efficiently isolate compounds with high purity from O. falcata because of the complexity of traditional Tibetan medicines. In this study, the 80% ethanol elution fraction from extract by AB-8 macroporous resin column chromatography was demonstrated to have anticancer activity on human hepatoma SMMC-7721 cells in vitro. Then, a high-speed counter-current chromatography (HSCCC) method was successfully established for separation of compounds by using hexane–ethyl acetate–methanol–water (10:4:10:10, v/v/v/v) as the solvent system. Five flavonoids (7-hydroxyflavonone [1], 5,7-dihydroxy-4′-methoxy flavonol [2], 5,7-dihydroxyflavanone [3], 2′,4′-dihydroxychalcone [4], and 2′,4′-dihydroxydihydrochalcone [5]) were obtained in one-step separation with purities of 97.7%, 98.1%, 98.3%, 99.0%, and 98.3%, respectively. Finally, anticancer activities against the growth of SMMC-7721 cells of 5 flavonoids were confirmed. The IC50 values of the separated compounds were 213.45 μg/mL, 197.74 μg/mL, 375.16 μg/mL, 17.44 μg/mL, and 136.83 μg/mL in 24 h, respectively. The present study provided a basis for further development and utilization of this medicinal herb as a source of a new potential anticancer agent.
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Scutellaria L. is a diverse genus of the Lamiaceae (Labiatae) family of over 300 herbaceous plants commonly known as skullcaps. Various species of Scutellaria are used as ethnobotanical herbs for the treatment of ailments like cancer, jaundice, cirrhosis, anxiety, and nervous disorders. Scutellaria incana L., commonly known as the Hoary skullcap, is a traditional medicinal plant used by native Americans as a sedative for nervousness or anxiety. S. incana metabolites were identified by comparing their high-performance liquid chromatography (HPLC) retention times and mass spectra with those of the corresponding authentic standards. Where standards were unavailable, the structures were characterized on the basis of their tandem mass spectrometry (MS/MS) spectra following collision-induced dissociation (CID) and the accurate masses of the corresponding deprotonated molecules [M-H]− (mass accuracy ± 5 ppm). A total of 40 flavonoids, including two phenolic glycosides, were identified from leaves, stems, and roots of S. incana. Differences in the flavonoid composition between leaves, stems, and roots in S. incana were observed although the flavonoid profile of S. incana is consistent with other Scutellaria species. Further work should focus on assessing the potential of S. incana as a source of these bioactive metabolites.
Purpose: Glycosaminoglycans (GAGs) and proteoglycans (PG) in addition to collagen are the main components of extracellular matrix (ECM). They play an important role in intercellular communication and interactions between cells and ECM. The biological changes in ECM that occur during aging are induced by decrease in GAG biosynthesis. The purpose of this study was to evaluate the effect of selected flavonoids isolated from Cirsium palustre (L.) Scop. on GAG content in human skin fibroblasts. Materials and methods: Human skin fibroblasts were treated with eriodictyol 7-O-glucoside (C1), 6-hydroxyluteolin 7-O-glucoside (C2), scutellarein 7-O-glucoside (C3) and pedalitin (C4) at 1, 20 and 40 μM for 24 h. Concentration of GAGs in the medium was assayed using method based on their ability to bind the cationic dye 1,9- dimethylmethylene blue (DMMB). Results: C1, C2 and C4 at concentration of 20 and 40 µM significantly increased content of sulphated GAGs in the medium. In contrast, treatment of cells with compound C3 did not have a statistically significant impact on GAG level. Ascorbic acid used as a positive control at 50 µM showed no effect on GAG concentration and increased their content at 100 µM but to a much lower extent than flavonoids. Conclusion: Flavonoids C1, C2 and C4 showed greater than ascorbic acid stimulatory impact on GAGs in healthy human skin fibroblasts, demonstrating their therapeutic potential in the aging.