Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme

Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3′-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC50 = 0.2–0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC50 = 1.8 μM) with higher potency vs. 6-MP oxidation (IC50 = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC50 = 0.2–0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC50 = 7.0 μM), and induced more potent inhibition compared to quercetin (IC50 = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin–drug interactions (e.g., with 6-mercaptopurin or azathioprine).

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Identification of chemical constituents from the bark of Larix kaempferi and their tyrosinase inhibitory effect

Holzforschung ◽

10.1515/hf-2018-0267 ◽

2019 ◽

Vol 73 (7) ◽

pp. 637-643 ◽

Cited By ~ 2

Author(s):

Yuya Kakumu ◽

Kosei Yamauchi ◽

Tohru Mitsunaga

Keyword(s):

Chemical Constituents ◽

Inhibitory Effect ◽

Positive Control ◽

Hydroxyl Group ◽

Larix Kaempferi ◽

Tyrosinase Inhibition ◽

Ionization Time ◽

Flight Mass Spectrometry ◽

Potent Inhibition ◽

Forestry Production

Abstract Most of the wood bark produced by the forestry production is discarded in spite of containing many kinds of the phytochemical ingredients. The aim of the present study was to identify secondary metabolites from the bark of Larix kaempferi generated as waste material and evaluate their potential as cosmetic agents. Eighteen compounds, including a novel phenanthrene, 4,6,7-trihydroxyphenanthrene-2-O-β-D-glucopyranoside (16), were isolated from the bark of L. kaempferi and identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance (NMR). In addition, the tyrosinase inhibitory activity of these compounds was evaluated. Procyanidin B7 (18) exhibited the most potent inhibition with IC50 values of 31.0 μM and 61.8 μM when using L-tyrosine and L-dopa as the substrate, respectively, which were similar to those of the positive control, kojic acid. Interestingly, quercetin-3-O-α-L-rhamnopyranoside (10) was shown to possess the tyrosinase inhibition although the other series of 3-glycoylated flavonols were not active, suggesting that the rhamnosyl group at C-3 and the hydroxyl group at C-3ʹ played an indispensable role in the anti-tyrosinase activity. These findings indicate that a number of constituents from L. kaempferi bark may have potential as additives in cosmetics.

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Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment, counteract the strong inhibitory effect of polyphenols from brown sorghum on the absorption of fortification iron in young women

British Journal Of Nutrition ◽

10.1017/s0007114513002705 ◽

2013 ◽

Vol 111 (3) ◽

pp. 481-489 ◽

Cited By ~ 22

Author(s):

Colin I. Cercamondi ◽

Ines M. Egli ◽

Christophe Zeder ◽

Richard F. Hurrell

Keyword(s):

Ascorbic Acid ◽

Polyphenol Oxidase ◽

Young Women ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Fe Isotopes ◽

Absorption Studies ◽

Oxidase Enzyme ◽

Strong Inhibitory Effect

In addition to phytate, polyphenols (PP) might contribute to low Fe bioavailability from sorghum-based foods. To investigate the inhibitory effects of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe absorption studies in fifty young women consuming dephytinised Fe-fortified test meals based on white and brown sorghum varieties with different PP concentrations. Fe absorption was measured as the incorporation of stable Fe isotopes into erythrocytes. In study 1, Fe absorption from meals with 17 mg PP (8·5 %) was higher than that from meals with 73 mg PP (3·2 %) and 167 mg PP (2·7 %;P< 0·001). Fe absorption from meals containing 73 and 167 mg PP did not differ (P= 0·9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167 mg PP) was higher than that from the same meals fortified with FeSO4(4·6v.2·7 %;P< 0·001), but still it was lower than that from FeSO4-fortified meals with 17 mg PP (10·7 %;P< 0·001). In study 3, laccase treatment decreased the levels of PP from 167 to 42 mg, but it did not improve absorption compared with that from meals with 167 mg PP (4·8v.4·6 %;P= 0·4), whereas adding AA increased absorption to 13·6 % (P< 0·001). These findings suggest that PP from brown sorghum contribute to low Fe bioavailability from sorghum foods and that AA and, to a lesser extent, NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect of PP and improve Fe absorption from sorghum foods.

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The Inhibitory Effect ofPrunella vulgarisL. on Aldose Reductase and Protein Glycation

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/928159 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Hong Mei Li ◽

Jin Kyu Kim ◽

Jai Man Jang ◽

Sang Oh Kwon ◽

Cheng Bi Cui ◽

...

Keyword(s):

Aldose Reductase ◽

Inhibitory Effect ◽

Protein Glycation ◽

Prunella Vulgaris ◽

Inhibitory Effects ◽

Advanced Glycation ◽

High Concentration ◽

Potent Inhibition ◽

Glycation End Products

To evaluate the aldose reductase (AR) enzyme inhibitory ability ofPrunella vulgarisL. extract, six compounds were isolated and tested for their effects. The components were subjected toin vitrobioassays to investigate their inhibitory assays using rat lens aldose reductase (rAR) and human recombinant AR (rhAR). Among them, caffeic acid ethylene ester showed the potent inhibition, with the IC50values of rAR and rhAR at3.2±0.55 μM and12.58±0.32 μM, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, this compound showed noncompetitive inhibition against rhAR. Furthermore, it inhibited galactitol formation in a rat lens incubated with a high concentration of galactose. Also it has antioxidative as well as advanced glycation end products (AGEs) inhibitory effects. As a result, this compound could be offered as a leading compound for further study as a new natural products drug for diabetic complications.

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Efficacy of Arabic Coffee and Black Tea in Reducing Halitosis: A Randomized, Double-Blind, Controlled, Crossover Clinical Trial

Healthcare ◽

10.3390/healthcare9030250 ◽

2021 ◽

Vol 9 (3) ◽

pp. 250

Author(s):

Hamad Alzoman ◽

Ahmed Alzahrani ◽

Khaled Alwehaiby ◽

Waleed Alanazi ◽

Mohammed AlSarhan

Keyword(s):

Clinical Trial ◽

Cetylpyridinium Chloride ◽

Black Tea ◽

Inhibitory Effect ◽

Positive Control ◽

Negative Control ◽

Inhibitory Effects ◽

Breath Sample ◽

Double Blind ◽

Pre Treatment

The aim of the study was to objectively evaluate the short-term effect of Arabic coffee and black tea on oral halitosis. This study was a single-center, randomized, double-blind, placebo-controlled, crossover clinical trial on 17 healthy individuals. During the initial visit, pre-treatment breath samples were collected from each subject and analyzed using portable gas chromatography (OralChroma™). Four interventions were evaluated, with Arabic coffee and black tea as the test intervention tools, mouthwash containing a solution (0.05% chlorhexidine, 0.05% cetylpyridinium chloride, and 0.14% zinc lactate (CHX-CPC-Zn)) as a positive control, and drinking water as a negative control. Halitosis was induced by rinsing with 10 mL solution of L-cysteine for 30 s. Twenty minutes later, a breath sample was taken to record the baseline volatile sulfur compounds (VSC) levels (T0). Then, the participants were asked to rinse with 10 mL of a randomly-assigned solution for 30 s. Sixty minutes later, another breath sample was recorded (T1). Finally, after 120 min, the final breath sample was recorded (T2). It was found that rinsing with Arabic coffee decreased the level of H2S both in the first hour (T1) and the second hour (T2). The reduction was significantly greater at T1 (p = 0.017). There was a similar result after the volunteers rinsed with black tea. At T2, Arabic coffee showed a substantially greater reduction in H2S (p < 0.001). On the contrary, using CHX-CPC-Zn showed a significant and continuous decrease in H2S values in the breath throughout the experiment (p < 0.001). Water showed no significant impact on the level of VSC (p = 0.71). This study demonstrates that black tea and Arabic coffee had inhibitory effects on halitosis that was greater in the first hour and was not sustained over a long period. Additionally, Arabic coffee had a greater inhibitory effect on halitosis than black tea.

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Inhibition of Xanthine Oxidase-Catalyzed Xanthine and 6-Mercaptopurine Oxidation by Flavonoid Aglycones and Some of Their Conjugates

International Journal of Molecular Sciences ◽

10.3390/ijms21093256 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3256

Author(s):

Violetta Mohos ◽

Eszter Fliszár-Nyúl ◽

Miklós Poór

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Positive Control ◽

Acid Formation ◽

Limited Information ◽

Inhibitory Effects ◽

Flavonoid Aglycones ◽

Natural Phenolic Compounds ◽

The Impact

Flavonoids are natural phenolic compounds, which are the active ingredients in several dietary supplements. It is well-known that some flavonoid aglycones are potent inhibitors of the xanthine oxidase (XO)-catalyzed uric acid formation in vitro. However, the effects of conjugated flavonoid metabolites are poorly characterized. Furthermore, the inhibition of XO-catalyzed 6-mercaptopurine oxidation is an important reaction in the pharmacokinetics of this antitumor drug. The inhibitory effects of some compounds on xanthine vs. 6-mercaptopurine oxidation showed large differences. Nevertheless, we have only limited information regarding the impact of flavonoids on 6-mercaptopurine oxidation. In this study, we examined the interactions of flavonoid aglycones and some of their conjugates with XO-catalyzed xanthine and 6-mercaptopurine oxidation in vitro. Diosmetin was the strongest inhibitor of uric acid formation, while apigenin showed the highest effect on 6-thiouric acid production. Kaempferol, fisetin, geraldol, luteolin, diosmetin, and chrysoeriol proved to be similarly strong inhibitors of xanthine and 6-mercaptopurine oxidation. While apigenin, chrysin, and chrysin-7-sulfate were more potent inhibitors of 6-mercaptopurine than xanthine oxidation. Many flavonoids showed similar or stronger (even 5- to 40-fold) inhibition of XO than the positive control allopurinol. Based on these observations, the extremely high intake of flavonoids may interfere with the elimination of 6-mercaptopurine.

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In Vitro Anti-inflammatory and Xanthine Oxidase Inhibitory Activity of Tephrosia purpurea Shoot Extract

Natural Product Communications ◽

10.1177/1934578x1100601006 ◽

2011 ◽

Vol 6 (10) ◽

pp. 1934578X1100601 ◽

Cited By ~ 5

Author(s):

Shivraj H. Nile ◽

Chandrahasy N. Khobragade

Keyword(s):

Xanthine Oxidase ◽

Inhibitory Activity ◽

Positive Control ◽

Inflammatory Activity ◽

Cow Milk ◽

Diene Conjugate ◽

Tephrosia Purpurea ◽

Oxidase Enzyme ◽

Anti Inflammatory

The methanolic extract of Tephrosia purpurea (Leguminosae) shoots was evaluated in-vitro for its anti-inflammatory and xanthine oxidase inhibitory activity. Anti-inflammatory activity was measured by the Diene-conjugate, HET-CAM and β-glucuronidase methods. The enzyme inhibitory activity was tested against isolated cow milk xanthine oxidase. The average anti-inflammatory activity of T. purpurea shoot extract in the concentration range of 1-2 μg/mL in the reacting system revealed significant anti-inflammatory activities, which, as recorded by the Diene-conjugate, HET-CAM and β-glucuronidase assay methods, were 45.4, 10.5, and 70.5%, respectively. Screening of the xanthine oxidase inhibitory activity of the extract in terms of kinetic parameters revealed a mixed type of inhibition, wherein the Km and Vmax values in the presence of 25 to 100 μg/mL shoot extract was 0.20 mM/mL and 0.035, 0.026, 0.023 and 0.020 μg/min, while, for the positive control, the Km and Vmax values were 0.21 mM/mL and 0.043 μg/min, respectively. These findings suggest that T. purpurea shoot extract may possess constituents with good medicinal properties that could be exploited to treat the diseases associated with oxidative stress, xanthine oxidase enzyme activity and inflammation.

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In-vitro assessment of CYP3A4 and CYPC29 inhibition potential of Lupeol using human liver microsomes

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i2.2562 ◽

2019 ◽

Vol 9 (2) ◽

pp. 231-236

Author(s):

LAXMAN DATTU KHATAL ◽

Harinath More

Keyword(s):

Drug Interactions ◽

Human Liver ◽

Biological Activities ◽

Liver Microsomes ◽

Inhibitory Effect ◽

Positive Control ◽

Human Liver Microsomes ◽

Metabolite Formation ◽

Physiological Concentration

Background: Lupeol is a dietary triterpene, possesses numerous biological activities. Lupeol is currently under development for chemotherapy and chemoprevention. The aim of present study was to determine the potential inhibitory effect of Lupeol on cytochrome P450 (CYP3A4 and CYP2C9 isozymes) activities in human liver microsomes (HLM). Methods: The inhibition studies were conducted using testosterone 6β-hydroxylase (CYP3A4), and diclofenac 4’-Hydroxylase (CYP2C9) activity assay using positive control Ketoconazole and Sulphaphenazole, respectively. Inhibition study was performed by incubating lupeol (0 to 20 μM) with human liver microsomes, and the metabolite formation was analyzed by liquid chromatography-Tandem Mass Spectrometry (LC-MS/MS). Results: Luepol did not inhibit CYP3A4 and CYP2C9 isozymes mediated activities in human liver microsomes up to a maximum tested concentration of 20µM based on solubility under tested invitro conditions. Conclusions: Lupeol is not an inhibitor of the CYP3A4 and CYP2C9 isozymes. IC50 is greater than highest tested concentration as well as physiological concentration, where effect was measured with confidence. Therefore, clinically relevant pharmacokinetic herb-drug interactions are unlikely to occur between Lupeol and co-administered substrates of these CYP isozymes. Looking at the spectrum of biological activities and CYP inhibition potential of Lupeol; Lupeol can be used as adjuvant/ chemotherapy agent/ chemopreventive agent in therapy. Keywords: Lupeol, HLM, CYP3A4 and CYP2C9, Inhibition, herb–drug interactions

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Inhibitory Effect of Japanese Traditional Kampo Formula Frequently Prescribed in Gynecological Clinics on CYP3A4

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4259603 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Hao Ni ◽

Takashi Matsumoto ◽

Junko Watanabe ◽

Toshiaki Makino

Keyword(s):

Small Intestine ◽

Drug Interaction ◽

Grapefruit Juice ◽

Drug Information ◽

Herbal Medicines ◽

Inhibitory Effect ◽

Positive Control ◽

Inhibitory Effects ◽

Number Of Patients

Recently, the use of herbal medicines has become popular, and information on drug interactions between herbal medicines and chemical drugs is needed in clinics. In Japan, the number of patients taking Japanese traditional Kampo medicines has been increasing, and the proper drug information about herb-drug interaction is highly demanded. The most established herb-drug interaction is the case of grapefruit juice (GFJ) via the inhibition on CYP3A4 expressed in the small intestine. In the present study, we compared the inhibitory titer on CYP3A4 between the target Kampo products and GFJ used as positive control. We evaluated the inhibitory effects of GFJ and three extracts of Kampo formulas frequently used in gynecological clinics on CYP3A4 in vitro and calculated the related titer of one-time dosage of Kampo formulas to GFJ in order to predict its effect on clinics. Although the extracts of these three Kampo formulas and the most of crude drug components in the formulas exhibited the inhibitory effects on CYP3A4 in some levels, the possibilities of tokishakuyakusan and keishibukuryogan to cause drug interaction can be quite low; however, it is possible that the excessive dosage of kamishoyosan may cause drug interaction with the substrate of CYP3A4 in clinics.

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Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000652 ◽

2020 ◽

pp. 1-9

Author(s):

Pınar Ercan ◽

Sedef Nehir El

Keyword(s):

Inhibitory Activity ◽

Digestive Enzymes ◽

Positive Control ◽

Anthocyanin Content ◽

Inhibitory Effects ◽

Total Anthocyanin ◽

Total Anthocyanin Content ◽

Before And After ◽

Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

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In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646570 ◽

1989 ◽

Vol 61 (02) ◽

pp. 254-258 ◽

Cited By ~ 21

Author(s):

Margaret L Rand ◽

Peter L Gross ◽

Donna M Jakowec ◽

Marian A Packham ◽

J Fraser Mustard

Keyword(s):

Cyclic Amp ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Inhibitory Effects ◽

Low Concentrations ◽

Rabbit Platelets ◽

High Concentrations ◽

In Vitro Effects ◽

Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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