Quercetin Pentaacetate Research Articles

Design of a sustainable light-up flavonol probe for dual-ratiometric fluorescent sensing and visual differentiating ammonia and hydrazine.

Ammonia (NH3) and hydrazine (N2H4) present potential risks to human health, food and environmental safety. A sustainable flavonol-based probe, quercetin pentaacetate (QPA, weak blue emission 417nm), was fabricated for dual-ratiometric fluorescent sensing and visual differentiating NH3 and N2H4. Excited state intramolecular proton transfer-on products with green (487nm) and yellow (543nm) emissions occurred as meeting with NH3 and N2H4, respectively, for their different nucleophilicities. Such a promising response offered a great opportunity of QPA to discriminatively detect NH3 and N2H4 with large Stokes shifts (>122nm), high sensitivity (limit of detection: 35.4μM and 0.70ppm for NH3 solution and gas; 0.26μM for N2H4 solution), excellent accuracy (spiked recoveries from 98.6 % to 105 %), and superior selectivity. Importantly, QPA was utilized for monitoring NH3 vapor in fish spoilage procedures and detecting N2H4 in water samples for food and environmental safety evaluation.

The Immunomodulatory Aspect of Quercetin Penta Acetate on Th17 Cells Proliferation and Gene Expression in Multiple Sclerosis.

The function of Th17 cells in the neuroinflammatory process in multiple sclerosis (MS) has been previously clarified. It has been suggested that Quercetin can influence MS due to a variety of anti-inflammatory effects. The present study aimed to examine in vitro immunomodulatory aspects of Quercetin Penta Acetate as a modified compound on Th17 cells of MS patients and also to compare its effects with Quercetin. In this experimental study, peripheral blood mononuclear cell (PBMCs) were isolated and stained with CFSE then, half-maximal inhibitory concentration (IC50) values were determined using different doses and times for Quercetin Penta Acetate, and Methyl Prednisolone Acetate. Th17 cell proliferation was analyzed by flow cytometry and the expression levels of IL-17 and RORc genes were assessed by real-time polymerase chain reaction (PCR) method. The results showed that IL-17 gene expression was inhibited by Quercetin Penta Acetate (P=0.0081), but Quercetin Penta Acetate did not have a significant inhibitory effect on Th17 cells proliferation (P= 0.59) and RORc gene expression (P=0.1), compared to Quercetin. Taken together, our results showed some immunomodulatory aspects of Quercetin Penta Acetate on Th17 cells are more effective than Quercetin and it could be considered in the treatment of MS.

From LC-MS/MS metabolomics profiling of Kanchanara Guggulu to molecular docking and dynamics simulation of quercetin pentaacetate with aldose reductase.

Kanchanara Guggulu (KG) is an important traditional medicine that is prescribed by the Ayurveda physicians for the treatment of swellings in various organs such as the thyroid, and lymph nodes. High-resolution mass-spectrometry-based metabolomics found metabolites in KG. LC-MS/MS-based metabolomics analysis of KG identified 2,579 compounds including quercetin and kaempferol derivatives. The molecular docking and dynamics analysis of quercetin pentaacetate with aldose reductase is documented for further consideration in drug discovery.

Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative.

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion

Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. Natural products show exceptional structural diversity and they have played a vital role in drug research. Several investigations focused on applied structural modification of natural products to improved metabolic stability, solubility and biological actions them. Quercetin is a flavonoid that presents several biological activities, including anti-hRSV role. Some works criticize the pharmacological use of Quercetin because it has low solubility and low specificity. In this sense, we acetylated Quercetin structure and we used in vitro and in silico assays to compare anti-hRSV function between Quercetin (Q0) and its derivative molecule (Q1). Q1 shows lower cytotoxic effect than Q0 on HEp-2 cells. In addition, Q1 was more efficient than Q0 to protect HEp-2 cells infected with different multiplicity of infection (0.1–1 MOI). The virucidal effects of Q0 and Q1 suggest interaction between these molecules and viral particle. Dynamic molecular results suggest that Q0 and Q1 may interact with F-protein on hRSV surface in an important region to adhesion and viral infection. Q1 interaction with F-protein showed ΔG= -14.22 kcal/mol and it was more stable than Q0. Additional, MTT and plate assays confirmed that virucidal Q1 effects occurs during adhesion step of cycle hRSV replication. In conclusion, acetylation improves anti-hRSV Quercetin effects because Quercetin pentaacetate could interact with F-protein with lower binding energy and better stability to block viral adhesion. These results show alternative anti-hRSV strategy and contribute to drug discovery and development.

Molecular Docking Studies Of Natural Phenolic Compound and Derivates With Phospholipase A2

The enzyme phospholipase A2 (PLA2) catalyzes the conversion of membrane phospholipids in the inflammatory mediators, such as prostaglandins and leukotrienes. Because of this role, substances with inhibitory activity of PLA2 enzyme, has gained prominence in the scientific community like possible anti-inflammatory. Several studies have shown that phenolic compounds such as flavonoids, phenolic acids and other, has, among various biological activities, anti-inflammatory activity by inhibition of the enzyme PLA2. Based on this context, this study aimed to conduct a molecular docking study of various natural phenolic compounds and some of their derivatives forward to the enzyme PLA2. The crystallographic structure of PLA 2 was obtained from Target Database Protein Data Bank [PDB ID: 1KPM] and the ligands were obtained from PubChem Database. The docking was performed using the AutoDock 4.0 software. It was observed that among the phenolic compounds included in the study, those with better interaction with the enzyme were rosmarinic acid 3'-O-beta-glucoside, 4-nerolidylcatechol, rosmarinic acid methyl ester, quercetin 3-O-malonylglucoside, quercetin pentaacetate and rosmarinic acid, respectively. The present study provides a better understanding of the inhibition of PLA2 by phenolic compounds, which may contribute to the development of new anti-inflammatories. DOI: http://dx.doi.org/10.17807/orbital.v10i6.981

Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae)

Ethnopharmacological relevanceHeterotheca ineuloides Cass (Asteraceae), popularly known as árnica mexicana, is widely used in Mexican traditional medicine to treat bruises, dermatological problems, rheumatic pains, and other disorders as cancer. The major constituents in H. inuloides are cadinane type sesquiterpenes, flavonoids and phytosterols. Compounds with a cadinane skeleton have been proved to possess cytotoxic activity against human-tumor cell lines and brine shrimp, and display toxic effects in different animal species. Although this plant has been widely used, there is little available information on the safety and toxicity especially of pure compounds. Aim of this studyEvaluate the potential toxicity of the natural products isolated from H. inuloides and some semisynthetic derivatives. Materials and methodsThe toxic aspects of the following natural products isolated from dried flowers of H. inuloides: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), (1R,4R)-1-hydroxy-4H-1,2,3,4- tetrahydrocadalen-15-oic acid (4), D-chiro-inositol (5), quercetin (6), quercetin-3,7,3′-trimethyl ether (7), quercetin-3,7,3′,4′-tetramethyl ether (8), eriodictyol-7,4′-dimethyl ether (9), α-spinasterol (10), caryolan-1,9β-diol (11) and 7-(3,3-dimethylallyloxy)-coumarin (12) as well as the toxic aspects of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (13), 7-benzoxy-3,4-dihydrocadalene (14), 7-acetoxycadalene (15), 7-benzoxycadalene (16), quercetin pentaacetate (17), 7-hydroxycalamenene (18), 3,8-dimethyl-5-(1-methylethyl)-1,2-naphthoquinone (19), and 4-isopropyl-1,6-dimethylbenzo[c]oxepine-7,9-dione (20). Toxic activities of compounds were determined by sulforhodamine B (SRB) assay, Artemia salina assay, RAW264.7 macrophage cells. Additionally, the acute toxicity in mouse of compound 1, the major natural sesquiterpene isolated from the acetone extract, was evaluated. ResultsThe best cytotoxicity activity was observed for mansonone C (19) on K562 cell line with IC50 1.45±0.14μM, for 7-hydroxycadalene (2) on HCT-15 cell line with IC50 18.89±1.2μM, and for quercetin pentaacetate (17) on MCF-7 cell line with IC50 22.57±2.4μM. Sesquiterpenes mansonone C (19) and 7-hydroxy-3,4-dihydrocadalene (1) caused the strongest deleterious effects against A. salina with IC50 39.4±1.07, and 45.47±1.74μM, respectively. The number of viable RAW 264.7 cells was reduced with sesquiterpenes 1 and 2 by more than 90%. In addition, the acute study of 1 revealed no lethal effects at 300mg/kg body weight, however, a reduction in the body weight of mice, morphological changes in the tissues of the liver and kidney and toxic signs were observed at very high doses (2000mg/kg). ConclusionThe results provided evidence for the cytotoxicity of Mexican arnica (H. inuloides) metabolites and may be correlated with one of the popular uses of this plant, in traditional Mexican medicine, as anticancer remedy. Among the active compounds contained in the acetone extract, the cytotoxic activity is mainly ascribable to cadinene type sesquiterpenes. In addition, evidence of acute toxicity suggests that 7-hydroxy-3,4-dihydrocadalene (1) may lead to toxicity at very high doses.

How Sorbitan Monostearate Can Increase Drug-Loading Capacity of Lipid-Core Polymeric Nanocapsules.

Lipid-core polymeric nanocapsules are innovative devices that present distinguished characteristics due to the presence of sorbitan monostearate into the oily-core. This component acted as low-molecular-mass organic gelator for the oil (medium chain triglycerides). The organogel-structured core influenced the polymeric wall characteristics disfavoring the formation of more stable polymer crystallites. This probably occurred due to interpenetration of these pseudo-phases. Sorbitan monostearate dispersed in the oily-core was also able to interact by non-covalent bonding with the drugs increasing the drug loading capacity more than 40 times compared to conventional nanocapsules. We demonstrated that the drug-models quercetin and quercetin pentaacetate stabilized the organogel network probably due to interactions of the drug molecules with the sorbitan monostearate headgroups by hydrogen bonding.

In vitro activity of ‘Mexican Arnica’ Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis

Giardiasis is a gastrointestinal disease that affects humans and other animals caused by parasitic protists of the genus Giardia. Giardia intestinalis (Syn. Giardia lamblia; Giardia duodenalis) infections can cause acute or chronic diarrhoea, dehydration, abdominal discomfort and weight loss. Metronidazole is the most widely used drug for treating giardiasis. Although effective, metronidazol has undesirable secondary effects. Plants used in traditional medicine as antidiarrhoeals or antiparasitics may represent alternative sources for new compounds to treat giardiasis. Heterotheca inuloides Cass. (Asteraceae/Compositae) plant is widely used in Mexican traditional medicine. The following secondary metabolites were isolated from H. inuloides flowers: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), 1R,4R-hydroxy-1,2,3,4-tetrahydrocadalen-15-oic acid (4), quercetin (5), quercetin-3,7,3'-trimethyl ether (6), quercetin-3,7,3',4'-tetramethyl ether (7) and eriodictyol-7,4'-dimethyl ether (8). The activity of these compounds against Giardia intestinalis trophozoites was assessed in vitro as was the activity of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (9), 7-benzoxy-3,4-dihydrocadalene (10), 7-acetoxycadalene (11), 7-benzoxycadalene (12), quercetin pentaacetate (13) and 7-hydroxycalamenene (14). Among these, 7-hydroxy-3,4-dihydrocadalene (1) and 7-hydroxycalamenene (14) were the most active, whereas the remaining compounds showed moderate or no activity. The G. intestinalis trophozoites exposed to compound 1 showed marked changes in cellular architecture along with ultrastructural disorganization. The aim of this study was to evaluate the giardicidal activity of selected H. inuloides metabolites and some semisynthetic derivatives using an in vitro experimental model of giardiasis.

A new approach to the design of antioxidants derived from 3,5,7,3′,4′-pentahydroxyflavone

Quercetin pentaacetate (Qu(OAc)5) was obtained by the acylation of quercetin by method (5) and then reduced with sodium metal in ethanol. The features of the electronic structure of the quercetin pentaacetate reduction product were studied by analyzing the ESR spectra of ketyl resulting from the dissociation of the corresponding pinacolate. Figure 1 shows the ESR spectrum of the sodium ketyl of acetylated quercetin. The calculation of the spin density distribution using the Priroda software allowed us to assign a doublet with а Н = 2 G in the spectrum of quercetin ketyl to the

Radical-scavenging and rat liver mitochondria lipid peroxidative inhibitory effects of natural flavonoids from traditional medicinal herbs

Baicalein (a), baicalin (b), daidzein (c), myricetin (d), oroxylin A (e), quercetin (f), quercetin pentaacetate (g), quercitrin (h), and wogonin (i) were isolated from regular anti-inflammatory Chinese herbs which contain many flavonoids compounds, also the radical-scavenging and liver mitochondrial lipid peroxidation (LPO) inhibitory capabilities were elucidated. The 50% inhibitory concentrations (IC50) for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capability of (a), (b), (d), (f), and (g) were 3.61, 3.28, 2.41, 2.16, and 3.74 μg/ml, and for LPO inhibition were 9.32, 9.52, 19.63, 16.15, and 20.22 μg/ml, respectively. The antioxidant capacities of (d), (f), (g), (h), (b), and (a) were 20.46, 16.42, 14.46, 13.98, 12.74, and 8.13 μMTrolox equivalents, respectively. To compare with the structure-activity relationships of the flavonoids, two flavones of baicalein and baicalin which have 5,6-hydroxy group which contain ortho-hydroxyl group characteristic reveal better LPO inhibitory activity, and two flavonols of myricetin, quercetin which have 5,7-trihydroxy group have more DPPH activity and ferrous chelating ability. The hydroxyl groups might play a role in increasing the activity of the flavonoids and exhibit potent antioxidant activities. In view of these results, five of the nine natural flavonoids (baicalein, baicalin, myricetin, quercetin and quercetin pentaacetate) can be lead compounds for preventing liver damage and related iron-overload disease. Key words: Anti-inflammatory Chinese herbs, ferrous ion, flavonoids, lipid peroxidation.

In silico study of the binding parameters of various antioxidants with human Paraoxonase 1

Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates. Human Paraoxonase 1 is synthesized in liver and secreted into blood, where it is associated exclusively with High Density Lipoproteins and may protect against the development of atherosclerosis. Paraoxonase was identified as a genetic risk factor for cardiovascular disease. An enhancement of Paraoxonase 1 activity by well-known anti oxidant flavonols like Quercetin and its derivatives are therefore of interest. The aim of this study is to investigate the binding parameters of Quercetin and its derivatives such as Quercetin dihydrate, Quercetin pentaacetate and Quercetin -3-methylether with Paraoxonase. Human Paraoxonase 1 was modeled using Modeller and binding parameters were studied using Arguslab software. The interactions show the differences in their binding and will throw light on new ways of effecting High Density Lipoprotein content and action. The docking studies helped in understanding the binding parameters thereby giving a direction for future anti-atherosclerotic treatment options. Key words: Paraoxonases, quercetin, anti-oxidant, high density lipoproteins (HDL), atherosclerosis.

Anti-inflammatory and Antioxidant Activity of a Methanolic Extract of Phyllanthus orbicularis and its Derived Flavonols

In order to validate the use of Phyllanthus orbicularis (Phyllantaceae) in the traditional medicine of Cuba as an anti-inflammatory remedy, the methanolic (MeOH) extract has been evaluated in vivo for anti-inflammatory activity on 12-O-tetradecanoyl-13-acetate phrobol (TPA) assay in mouse and in vitro for the antioxidant activity on Ferric Reduction Antioxidant Power assay. This extract exerted in vivo a significant anti-inflammatory activity. Subsequent fractionation and analysis of the extract has led to the isolation and characterization as major constituents of apigenin (1), rutin (quercetin 3-O—L-rhamnopyranosyl-(1->6)—D-glucopyranoside) (2) and quercetin (3) and of rutin decaacetate (4) and quercetin pentaacetate (5) from acetylated methanolic extract. Their structures were elucidated by spectral methods. The bioassay-directed analysis of flavonols 1–3 indicated that rutin (2) and quercetin (3) were the most active compounds, whereas apigenin showed no significant activity. The acetylation process increased the anti-inflammatory activity but decreased the antioxidant activity. The MeOH extract and all of flavonoids tested did not show in vitro significant cytotoxic effect in J774.A1 macrophage cell line. [Editor's note: The five compounds under discussion are denoted throughout this paper by bolded number (1, 2, etc.). This should not be confused with the referenced ancillary texts, denoted in non-bolded font and within parentheses.]

Prevention of benzene-induced genotoxicity in bone marrow and lung cells: superiority of polyphenolic acetates to polyphenols

Previous investigations carried out in our laboratory have highlighted that 7,8-diacetoxy-4-methylcoumarin demonstrates a mechanism-based inhibition of cytochrome P450 (Cyt-P450) activities such as microsome-mediated aflatoxin B1 (AFB1) epoxidation, dealkylation of alkylated resorufin, and toxicokinetics of benzene. 7,8-Diacetoxy-4-methylcoumarin, quercetin pentaacetate, and ellagic acid peracetate were also found to be effective in giving the protection of AFB1-induced genotoxicity in rat's bone marrow and lung cells possibly due to acetylation of Cyt-P450 apoprotein mediated by acetoxy drug: protein transacetylase. Later, this transacetylase was identified as calreticulin, and the acetyltransferase function of calreticulin was appropriately termed calreticulin transacetylase. In this communication, we have focused on the superiority of several classes of polyphenolic acetates to polyphenols in the modification of Cyt-P450-linked mixed function oxidases (MFOs) such as 7-ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-dealkylase (PROD). Special attention has also been focused on benzene-induced genotoxicity in bone marrow and lung cells. Results clearly indicated that polyphenolic acetates demonstrated time-dependent inhibition of Cyt-P450-linked MFOs, while parent polyphenols failed to demonstrate the same. Polyphenolic acetates were found to be more superior to polyphenols in preventing benzene-induced micronuclei formation. The pattern of inhibition of Cyt-P450-dependent MFOs and benzene-induced micronuclei formation by polyphenolic acetates was found in tune with their specificities to calreticulin transacetylase. These results further substantiated that inhibition of Cyt-P450-linked MFOs and benzene-induced genotoxicity in bone marrow and lung cells by polyphenolic acetates are mediated by the action of calreticulin transacetylase that catalyzes the acetylation of concerned proteins.

Cytotoxic Activities of Flavonoid Glycoside Acetates from Consolida oliveriana

The flavonoids kaempferol, quercetin, trifolin, hyperoside 2''- and 6''- acetates, 7-glucotrifolin, biorobin and robinin were isolated from the aerial parts of Consolida oliveriana. Their derivatives kaempferol tetraacetate, quercetin pentaacetate, trifolin heptaacetate and hyperoside octaacetate exhibited significant cytotoxicity IN VITRO against three human cell lines HL-60, U937 and SK-MEL-1 while hyperoside 2''-acetate, hyperoside-6''-acetate, glucotrifolin decaacetate and heptamethyltrifolin were inactive.

Ellagic acid peracetate is superior to ellagic acid in the prevention of genotoxicity due to aflatoxin B1in bone marrow and lung cells

Earlier observations carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins and quercetin pentaacetate in preventing the genotoxicity of aflatoxin B1 (AFB1). We have extended the observation to an acetoxy biscoumarin i.e. ellagic acid peracetate (EAPA), which unlike ellagic acid (EA) has demonstrated time-dependent inhibition of liver microsomes catalysed AFB1-epoxidation as measured by AFB1 binding to DNA. EAPA was more potent than EA in preventing bone marrow and lung cells from AFB1-induced genotoxicity. EAPA was acted upon by microsomal acetoxy drug:protein transacetylase (TAase) leading to modulation of the catalytic activity of certain functional proteins (cytochrome P450, NADPH cytochrome c reductase and glutathione S-transferase), possibly by way of protein acetylation.

Effect of flavonoids and Vitamin E on cyclooxygenase-2 (COX-2) transcription

Cyclooxygenase-2 (COX-2)-catalysed synthesis of prostaglandin E2 plays a key role in inflammation and its associated diseases, such as cancer and cardiovascular disease. There are numerous reports demonstrating that flavonoids inhibit COX-2 activity. However, transcriptional regulation of COX-2 can also be important. Nobiletin, amentoflavone, quercetin, quercetin penta-acetate, flavone, resveratrol, apigenin, chrysin, kaempferol, galangin, and genistein have been reported to modulate COX-2 transcription in a wide variety of systems. Here, we briefly review the literature on regulation of COX-2 transcription by flavonoids, and report some new preliminary data on Vitamin E and quercetin conjugates. Quercetin, quercetin 3-glucuronide, quercetin 3′-sulfate and 3′methylquercetin 3-glucuronide reduced COX-2 mRNA expression in both unstimulated and interleukin-1β stimulated colon cancer (Caco2) cells. Quercetin and quercetin 3′-sulfate, unlike quercetin 3-glucuronide and 3′methylquercetin 3-glucuronide, also inhibited COX-2 activity. In contrast, tocopherols (α-tocopherol, α-tocopherol acetate, and γ-tocopherol at 10 μM) did not affect COX-2 mRNA expression in unstimulated Caco2 cells. However, the tocopherols inhibited COX-2 activity showing that the tocopherols act post-transcriptionally on activity, whereas quercetin and some quercetin conjugates affect both the transcription and activity of COX-2. Flavonoid modulation of COX-2 transcription may therefore be an important mechanism in anti-carcinogenesis.

Comparison of the Prevention of Aflatoxin B 1-Induced Genotoxicity by Quercetin and Quercetin Pentaacetate

Earlier work carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins in preventing the genotoxicity of aflatoxin B 1 (AFB 1). We have in this report extended the observations to quercetin pentaacetate (QPA), which unlike quercetin (Q) has demonstrated time-dependent inhibition of liver microsome catalysed AFB 1 epoxidation as measured by AFB 1 binding to DNA. The action of QPA is similar to that of the acetoxy 4-methylcoumarins in that they are acted upon by microsomal transacetylase leading to modulation of catalytic activities of certain enzymes (such as P-450 enzymes, NADPH cytochrome C reductase and glutathione S-transferase) possibly by way of protein acetylation. In the present work, we have documented the transacetylase-mediated action of QPA in preventing genotoxicity due to AFB 1.

Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages.

Several natural flavonoids have been demonstrated to perform some beneficial biological activities, however, higher-effective concentrations and poor-absorptive efficacy in body of flavonoids blocked their practical applications. In the present study, we provided evidences to demonstrate that flavonoids rutin, quercetin, and its acetylated product quercetin pentaacetate were able to be used with nitric oxide synthase (NOS) inhibitors (N-nitro-L-arginine (NLA) or N-nitro-L-arginine methyl ester (L-NAME)) in treatment of lipopolysaccharide (LPS) induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions in a mouse macrophage cell line (RAW 264.7). The results showed that rutin, quercetin, and quercetin pentaacetate-inhibited LPS-induced NO production in a concentration-dependent manner without obvious cytotoxic effect on cells by MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide as an indicator. Decrease of NO production by flavonoids was consistent with the inhibition on LPS-induced iNOS gene expression by western blotting. However, these compounds were unable to block iNOS enzyme activity by direct and indirect measurement on iNOS enzyme activity. Quercetin pentaacetate showed the obvious inhibition on LPS-induced PGE2 production and COX-2 gene expression and the inhibition was not result of suppression on COX-2 enzyme activity. Previous study demonstrated that decrease of NO production by L-arginine analogs effectively stimulated LPS-induced iNOS gene expression, and proposed that stimulatory effects on iNOS protein by NOS inhibitors might be harmful in treating sepsis. In this study, NLA or L-NAME treatment stimulated significantly on LPS-induced iNOS (but not COX-2) protein in RAW 264.7 cells which was inhibited by these three compounds. Quercetin pentaacetate, but not quercetin and rutin, showed the strong inhibitory activity on PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS co-treated RAW 264.7 cells. These results indicated that combinatorial treatment of L-arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS-induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX-2 genes.

Mutagenic Activity of Quercetin and Related Compounds

The mutagenic activities of several flavonoids and flavonoid metabolites were examined by means of Salmonella typhimurium mutants that reveal base-pair substitution and frameshift mutagens. Of the compounds tested (naringin, rutin, neohesperetin, hesperetin, dihydroquercetin, quercetin, quercetin pentaacetate, permethylquercetin, m-hydroxyphenylacetic acid, and m,p-dihydroxyphenylacetic acid), only quercetin was mutagenic without microsomal activation. With activation, however, the mutagenic activity of quercetin was increased significantly and that of quercetin pentaacetate was revealed. The health implications of these findings and aspects of flavonoid structural requirements for mutagenic activity are discussed.