Inhibitory Effect Of Tannic Acid Research Articles

Discovery of a C-S lyase inhibitor for the prevention of human body malodor formation: tannic acid inhibits the thioalcohol production in Staphylococcus hominis.

Human body odor is a result of the bacterial biotransformation of odorless precursor molecules secreted by the underarm sweat glands. In the human axilla, Staphylococcus hominis is the predominant bacterial species responsible for the biotransformation process of the odorless precursor molecule into the malodorous 3M3SH by two enzymes, a dipeptidase and a specific C-S lyase. The current solutions for malodor, such as deodorants and antiperspirants are known to block the apocrine glands or disrupt the skin microbiota. Additionally, these chemicals endanger both the environment and human health, and their long-term use can influence the function of sweat glands. Therefore, there is a need for the development of alternative, environmentally friendly, and natural solutions for the prevention of human body malodor. In this study, a library of secondary metabolites from various plants was screened to inhibit the C-S lyase, which metabolizes the odorless precursor sweat molecules, through molecular docking and molecular dynamics (MD) simulation. In silico studies revealed that tannic acid had the strongest affinity towards C-S lyase and was stably maintained in the binding pocket of the enzyme during 100-ns MD simulation. We found in the in vitro biotransformation assays that 1 mM tannic acid not only exhibited a significant reduction in malodor formation but also had quite low growth inhibition in S. hominis, indicating the minimum inhibitory effect of tannic acid on the skin microflora. This study paved the way for the development of a promising natural C-S lyase inhibitor to eliminate human body odor and can be used as a natural deodorizing molecule after further in vivo analysis.

Inhibitory effect of tannic acid on the growth of Apiospora arundinis and 3-Nitropropionic acid production.

This study aimed to investigate the inhibitory effect of tannic acid (TA) on the growth of Apiospora arundinis and 3-Nitropropionic acid (3-NPA) production. To investigate the antifungal mechanism, the effects of TA on the hypha growth, electrical conductivity, hypha morphology, defense-related enzymes, and 3-NPA production of A. arundinis were studied. TA concentrations of 640 and 1280 μg ml-1 exhibited strong antifungal activity against A. arundinis. The results of scanning electron microscopy and transmission electron microscopy showed that the hypha of the A. arundinis was severely deformed after TA treatment, and the cell membrane was blurred and thin, vacuoles were obviously shrunken and smaller, and most of the organelles were decomposed into irregular fragments. The increased electrical conductivity and malondialdehyde content indicated that TA caused peroxidation of unsaturated fatty acids and damaged the structure of the cell membrane. The decrease of intracellular ATPase and succinate dehydrogenase content indicated that TA damaged the function of mitochondria, and participated in the inhibition of respiratory metabolism. In addition, TA significantly reduced 3-NPA production and completely inhibited 3-NPA production at 640 and 1280 μg ml-1. TA effectively inhibited both growth of A. arundinis in vitro and 3-NPA production.

α-Amylase Changed the Catalytic Behaviors of Amyloglucosidase Regarding Starch Digestion Both in the Absence and Presence of Tannic Acid

The courses of starch digestion with individual α-amylase (AA), amyloglucosidase (AMG), and AA/AMG bi-enzyme system were performed and analyzed by first-order-reaction equations in the absence and presence of tannic acid (TA). An antagonistic effect between AA and AMG occurred at the digestion phase of readily-digestible starch due to the higher catalytic efficiency of AMG for starchy-substrates with more complex structures. This effect caused a faster rate of glucose production with AMG than with AA/AMG bi-enzyme system at this phase both in the absence and presence of TA. TA had a higher binding affinity to AA than to AMG as accessed by several methods, such as inhibition kinetics, fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking. Besides, differential scanning calorimetry (DSC) indicated that the change in the thermal and structural stabilities of enzymes in the presence of TA was related to the enzyme residues involved in binding with TA, rather than the inhibitory effects of TA. The binding characters of TA to both enzymes resulted in more “free” AMG without TA binding in AA/AMG bi-enzyme system than that in individual AMG. This binding property caused more and faster rate of glucose production at the digestion phase of slowly digestible starch (SDS) in the bi-enzyme system.

Co-Application with Tannic Acid Prevents Transdermal Sensitization to Ovalbumin in Mice.

Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic stromal lymphopoietin and thymus and activation-regulated chemokine are also involved. In this study, we investigated the suppressive effect of tannic acid (TA) on transdermal sensitization using ovalbumin (OVA), a major egg-white allergen. We also analyzed the mechanisms associated with the inhibitory effects of TA. The results showed that the co-application with TA prevents transdermal sensitization to OVA. As possible mechanisms, its anti-inflammatory and astringent effect on the skin and binding ability with the protein were considered. These results indicate that TA could be applied to cosmetics and lotions, which could suppress the transdermal sensitization to allergens.

Effects of dietary crude protein and tannic acid on rumen fermentation, rumen microbiota and nutrient digestion in beef cattle

ABSTRACTThe objectives of the trial were to study the effects of dietary crude protein (CP) and tannic acid (TA) on rumen fermentation, microbiota and nutrient digestion in beef cattle. Eight growing beef cattle (live weight 350 ± 25 kg) were allocated in a 2 × 2 crossover design using two levels of dietary CP [111 g/kg dry matter (DM) and 136 g/kg DM] and two levels of TA (0 and 16.9 g/kg DM) as experimental treatments. Each experimental period lasted 19 d, consisting of 14-d adaptation and 5-d sampling. The impacts of dietary CP and TA on ruminal microbiota were analysed using high-throughput sequencing of 16S rRNA gene. Results indicated that no interactions between dietary CP and TA were found on rumen fermentation and nutrient digestibility. Increasing dietary CP level from 111 to 136 g/kg DM increased the ruminal concentrations of ammonia nitrogen (NH3-N) (p < 0.01) and improved the CP digestibility (p < 0.001). Adding TA at 16.9 g/kg DM inhibited rumen fermentation and decreased the digestibility of dietary CP (p < 0.001), DM (p < 0.05) and organic matter (p < 0.01). Increasing the dietary CP level or adding TA did not affect the relative abundances of the major bacteria Firmicutes and Proteobacteria at the phylum level and Prevotella_1 and Christensenellaceae_R-7_group at the genus level, even though adding TA increased the Shannon index of the ruminal bacterial community. TA was partly hydrolysed to pyrogallol, gallic acid and resorcinol in rumen fluid and the inhibitory effects of TA on rumen fermentation and nutrient digestibility could have been resulted from the TA metabolites including pyrogallol, gallic acid and resorcinol as well as the protein-binding effect.

Tannic acid affects the phenotype of Staphylococcus aureus resistant to tetracycline and erythromycin by inhibition of efflux pumps

The widespread use of antibiotics created selective pressure for the emergence of strains that would persist despite antibiotic toxicity. The bacterial resistance mechanisms are several, with efflux pumps being one of the main ones. These pumps are membrane proteins with the function of removing antibiotics from the cell cytoplasm. Due to this importance, the aim of this work was to evaluate the inhibitory effect of tannic acid against efflux pumps expressed by the Staphylococcus aureus RN4220 and IS-58 strains. The efflux pump inhibition was assayed using a sub-inhibitory concentration of efflux pump standard inhibitors and tannic acid (MIC/8), observing their capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. The MICs of EtBr and antibiotics were significantly different in the presence of tannic acid, indicating the inhibitory effect of this product against efflux pumps of both strains. These results indicate the possible usage of tannic acid asan inhibitor and an adjuvant in the antibiotic therapy against multidrug resistant bacteria (MDR).

Systematic studies of the interactions between a model polyphenol compound and microbial β-glucosidases.

Lignin is a major obstacle for cost-effective conversion of cellulose into fermentable sugars. Non-productive adsorption onto insoluble lignin fragments and interactions with soluble phenols are important inhibition mechanisms of cellulases, including β-glucosidases. Here, we examined the inhibitory effect of tannic acid (TAN), a model polyphenolic compound, on β-glucosidases from the bacterium Thermotoga petrophila (TpBGL1 and TpBGL3) and archaeon Pyrococcus furiosus (PfBGL1). The results revealed that the inhibition effects on β-glucosidases were TAN concentration-dependent. TpBGL1 and TpBGL3 were more tolerant to the presence of TAN when compared with PfBGL1, while TpBGL1 was less inhibited when compared with TpBGL3. In an attempt to better understand the inhibitory effect, the interaction between TAN and β-glucosidases were analyzed by isothermal titration calorimetry (ITC). Furthermore, the exposed hydrophobic surface areas in β-glucosidases were analyzed using a fluorescent probe and compared with the results of inhibition and ITC. The binding constants determined by ITC for the interactions between TAN and β-glucosidases presented the same order of magnitude. However, the number of binding sites and exposed hydrophobic surface areas varied for the β-glucosidases studied. The binding between TAN and β-glucosidases were driven by enthalpic effects and with an unfavorable negative change in entropy upon binding. Furthermore, the data suggest that there is a high correlation between exposed hydrophobic surface areas and the number of binding sites on the inhibition of microbial β-glucosidases by TAN. These studies can be useful for biotechnological applications.

Comparative evaluation of tannic acid inhibiting α-glucosidase and trypsin

In this work, the inhibitory effects of tannic acid on the α-glucosidase and trypsin were systematically evaluated by comparing with the clinical diabetes healer acarbose and the soybean-derived trypsin inhibitor using fluorescence spectroscopy and enzymatic kinetics methods. We showed that the anti-α-glucosidase activity of tannic acid (IC50=0.44μg/mL) was higher than that of acarbose (IC50>0.60μg/mL), while its anti-trypsin activity (IC50=0.79mg/mL) was significantly lower than that of the trypsin inhibitor from soybean (IC50<0.20mg/mL). Enzymatic kinetics measurements confirmed that the inhibitory pattern of tannic acid toward two tested enzymes was a mixed competitive and noncompetitive inhibition. Tannic acid could bind the enzymes to form new complexes, presenting a strong static fluorescence quenching. The presence of tannic acid led to the hypsochromic shift of the maximum fluorescence in trypsin, but not in α-glucosidase. The thermodynamic parameters indicated that the main driving force between tannic acid and both the enzymes was the hydrophobic interaction followed by the electrostatic interaction. Our work suggests that tannic acid is a strong anti-α-glucosidase natural inhibitor with a low inhibitory activity for trypsin, thus its roles in functional food and medicinal plants should be re-recognized.

Inhibitory effects of tannic acid in the early stage of 3T3-L1 preadipocytes differentiation by down-regulating PPARγ expression.

Obesity is a medical condition of excess body fat negatively influencing morbidity and mortality via non-communicable disease risks. Adipogenesis, the process in which preadipocytes differentiate into adipocytes, plays a pivotal role in obesity. Our previous study proved that tannic acid (TA) showed anti-adipogenesis effect in 3T3-L1 preadipocytes. However, the precise mechanism involved in the inhibition in adipocytes differentiation by TA is unclear, and thus this is the subject of the present investigation. In this study, we determined the effect of TA on different stages of 3T3-L1 preadipocytes differentiation, and found that when treating in the early stage of differentiation, TA reduced lipid accumulation significantly. However, TA did not reduce lipid accumulation when treating in mid- and late-stages of adipocyte differentiation. To further study which gene TA had an impact on in the early stage of differentiation, we identified a number of genes associated with lipid metabolism. The results showed that compared to the control group, the mRNA levels of FAS, C/EBPα, and PPARγ were significantly decreased (p < 0.05), whereas the mRNA levels of adipsin, ap2 were increased (p < 0.05). However, TA had no effect on mRNA levels of ACC1 and ACC2. Western blot results showed that TA down-regulated the expression of PPARγ, which is a major factor in preadipocyte differentiation. In addition, TA did not affect the PI3 K/AKT pathway. These results indicate that the anti-adipogenesis effect of TA involves down-regulation of PPARγ in the early stage of 3T3-L1 preadipocyte differentiation. Some potential limitations of this study should be considered. All the results in this study were based on cell experiments. However, the human bioavailability of TA is not clear. In the present study, the concentration of TA was 5 μM; therefore, there were concerns about whether oral intake of TA could reach the effective concentrations. This important point needs to be clarified in vivo.

Effects of tannic acid on Haemonchus contortus larvae viability and immune responses of sheep white blood cells in vitro

Direct inhibitory effects of tannic acid on Haemonchus contortus viability were studied in vitro using the larval migration inhibition (LMI) assay. Sheep white blood cells (WBC) were preincubated with 5 and 50 lg/mL tannic acid or not followed by whole H. contortus antigen (WHA). Cells were harvested at 24 h post-incubation to test host immune responses. Concentrations of 50, 100, 500, 1000, 3000 and 5000 lg/mL tannic acid inhibited larvae migration by 19.8, 42.4, 46.3, 92.0, 93.7 and 100%, respectively, within 96 h post-incubation (P < 0.001). The relative mRNA levels of interferon (IFN)-c, interleukin (IL)-2, IL-4 and IL-10 were increased by WHA stimulation without tannic acid. However, the increased effects on IFN-c and IL-2 were inhibited by tannic acid preincubation (P < 0.001), while the increases in IL-4 and IL-10 were greatly enhanced by tannic acid preincubation (P < 0.001). Changes in protein levels of all cytokines essentially paralleled the changes in their corresponding mRNA levels. In conclusion, tannic acid is directly harmful to larvae in a dose- and time-dependent manner and modulates immune responses of sheep WBC stimulated by H. contortus antigen by inhibiting Th1 cytokines and increasing Th2 cytokine expression in vitro.

Inhibitory effects of tannic acid on fatty acid synthase and 3T3-L1 preadipocyte

Tannic acid is a hydrolyzable tannin that exists in many widespread edible plants with a variety of biological activities. In this study, we found that tannic acid potently inhibited the activity of fatty acid synthase (FAS) in a concentration-dependent manner with a half-inhibitory concentration value (IC50) of 0.14μM. The inhibition kinetic results showed that the inhibition of FAS by tannic acid was mixed competitive and noncompetitive manner with respect to acetyl-CoA and malonyl-CoA, but uncompetitive to NADPH. Tannic acid prevented the differentiation of 3T3-L1 pre-adipocytes, and thus repressed intracellular lipid accumulation. In the meantime, tannic acid decreased the expression of FAS and down-regulated the mRNA level of FAS and PPARγ during adipocyte differentiation. Further studies showed that the inhibitory effect of tannic acid did not relate to FAS non-specific sedimentation. Since FAS was believed to be a therapeutic target of obesity, these findings suggested that tannic acid was considered having potential in the prevention of obesity.

Molecular Hairpin: A Possible Model for Inhibition of Tau Aggregation by Tannic Acid

Inhibition of anomalous aggregation of tau protein would be an attractive therapeutic target for Alzheimer's disease (AD). In this study, tannic acid (TA), a polymeric plant polyphenol, and its monomer, gallic acid (GA), were introduced as the references to afford a molecular framework that integrates tau binding properties and inhibitory effects. Using a thioflavin S fluorescence assay and electron microscopy, we demonstrated that TA could competently inhibit the in vitro aggregation of tau peptide R3, corresponding to the third repeat unit of the microtubule-binding domain, with an IC50 of 3.5 μM, while GA's inhibition was comparatively piddling (with an IC50 of 92 μM). In the isothermal titration calorimetry experiment, we found that TA could strongly bind to R3 with a large amount of heat released. Circular dichroism spectra showed TA dose-dependently suppressed the conformational transition of R3 from a random coil structure to a β-sheet structure during the aggregation process. Finally, a structural model was built using molecular docking simulation to elucidate the possible binding sites for TA on the tau peptide surface. Our results suggest that TA recognizably interacts with tau peptide by forming a hairpin binding motif, a key framework required for inhibiting tau polymerization, in addition to hydrogen bonding, hydrophilic-hydrophobic interactions, and static electrical interactions, as reported previously. The inhibitory effect of TA on human full-length tau protein (tau441) was also verified by electron microscopy. This finding hints at the possibility of TA as a leading compound of anti-AD drugs and offers a new stratagem for the rational molecular design of a tau aggregation inhibitor.

Effects of polyphenol oxidation onin vitroiron availability in faba bean (Vicia fabaL.) flour

Tannic acid (TA) and green tea extract (GTE) were added to faba bean flour, before and after incubation with polyphenol oxidase (mushroom tyrosinase), and the effect on in vitro iron availability was investigated. The inhibitory effect of TA and GTE was dose dependent, and the in vitro iron availability decreased from 64.5% in the pure faba bean flour to 9.8% (P < 0.05) with the addition of 1 mg of TA 1 g−1 to faba bean flour. The addition of 5 mg of GTE resulted in low in vitro iron availability as after the addition of 10 mg of TA (11.6% against 10.3% for 1 mg TA). Incubation of the polyphenols with tyrosinase before addition to the faba bean flour significantly increased the in vitro iron availability. The increase in iron availability was significant (P < 0.05) when amounts of 0.2, 0.5 or 1 mg g−1 TA or GTE added to faba bean flour, respectively, were oxidised, even with the lowest amount of tyrosinase (150 u). Oxidation of 1 mg TA or GTE with 150 u tyrosinase increased the in vitro iron availability from 10.3% to 15.5% and from 19.2% to 26.1%, respectively. At the 300-u level, the addition of higher amounts of enzyme (from 600 to 900 u) did not have any effect. The results from the study therefore suggest that the oxidation of polyphenols may be a promising way to increase the availability of iron in polyphenol-containing legume foods.

Evidence for an Enhancing Effect of Alginate on Iron Availability in Caco-2 Cells

The potential use of alginates as a vehicle for water-soluble (bioavailable) iron for fortifying food products was examined using a Caco-2 cell model system. Cell monolayers were exposed to alginates with various mannuronic to guluronic acid ratios at three different concentrations, and cellular ferritin was measured as a surrogate marker of iron uptake into the cell. Ferritin concentrations were significantly higher when the cells were treated with ferric ammonium citrate and 0.5 and 1% w/v (but not 0.1%) alginate, but were unaffected by mannuronic/guluronic acid ratios. The enhancing effect of ascorbic acid was maintained with 0.1% alginate and significantly increased with 0.5 and 1% alginate, whereas the inhibitory effect of tannic acid was significantly reduced with 0.5% alginate. Alginate beads delivered available iron to Caco-2 cells, indicating that they are a promising vehicle for soluble iron with potential use in food fortification programs.

Tannic Acid Down-Regulates the Angiotensin Type 1 Receptor Through a MAPK-Dependent Mechanism

In the present study, we investigated the effects of tannic acid (TA), a hydrolysable polyphenol, on angiotensin type 1 receptor (AT1R) expression in continuously passaged rat liver epithelial cells. Under normal conditions, exposure of cells to TA resulted in the down-regulation of AT1R-specific binding in concentrations ranging from 12.5-100 μg/ml (7.34-58.78 μm) over a time period of 2-24 h with no change in receptor affinity to angiotensin II (AngII). The inhibitory effect of TA on AT1R was specific and reversible. In TA-treated cells, we observed a significant reduction in AngII-mediated intracellular calcium signaling, a finding consistent with receptor down-regulation. Under similar conditions, TA down-regulated AT1R mRNA expression without changing the rate of mRNA degradation, suggesting that TA's effect is mediated through transcriptional inhibition. Cells expressing recombinant AT1R without the native promoter show no change in receptor expression, whereas a pCAT reporter construct possessing the rat AT1R promoter was significantly reduced in activity. Furthermore, TA induced the phosphorylation of MAPK p42/p44. Pretreatment of the cells with a MAPK kinase (MEK)-specific inhibitor PD98059 prevented TA-induced MAPK phosphorylation and down-regulation of the AT1R. Moreover, there was no reduction in AngII-mediated intracellular calcium release upon MEK inhibition, suggesting that TA's observed inhibitory effect is mediated through MEK/MAPK signaling. Our findings demonstrate, for the first time, that TA inhibits AT1R gene expression and cellular response, suggesting the observed protective effects of dietary polyphenols on cardiovascular conditions may be, in part, through inhibition of AT1R expression.

Studies on collagen-tannic acid-collagenase ternary system: Inhibition of collagenase against collagenolytic degradation of extracellular matrix component of collagen

We report the detailed studies on the inhibitory effect of tannic acid (TA) on Clostridium histolyticum collagenase (ChC) activity against degradation of extracellular matrix component of collagen. The TA treated collagen exhibited 64% resistance against collagenolytic hydrolysis by ChC, whereas direct interaction of TA with ChC exhibited 99% inhibition against degradation of collagen and the inhibition was found to be concentration dependant. The kinetic inhibition of ChC has been deduced from the extent of hydrolysis of N-[3-(2-furyl) acryloyl]-Leu-Gly-Pro-Ala (FALGPA). This data provides a selective competitive mode of inhibition on ChC activity seems to be influenced strongly by the nature and structure of TA. TA showed inhibitor activity against the ChC by molecular docking method. This result demonstrated that TA containing digalloyl radical possess the ability to inhibit the ChC. The inhibition of ChC in gaining new insight into the mechanism of stabilization of collagen by TA is discussed.

Tannic Acid Specific Inhibition of Angiotensin Type 1 Receptor in Rat Liver Epithelial Cells

Previous studies have shown that plant‐derived polyphenols appear to provide protection from hypertension. However, the target or mechanism of protective effects of polyphenols remains unclear. In the present study, we investigated the effects of tannic acid on angiotensin type 1 receptor (AT1R) expression. Exposure of rat liver epithelial cells to tannic acid resulted in significant down‐regulation of [3H]angiotensin II specific binding (81432±1981 to 40399±1952 dpm/mg protein) and AT1R protein (55%) and mRNA (60%) expression in a concentration and time dependent manner. The inhibitory effect of tannic acid on AT1R was specific and reversible. Under similar conditions, we observed increased phosphorylation of both MAP‐kinases (MAPK) p42 &amp; p44. Pretreatment of cells with MAPK specific inhibitor prevented tannic acid induced MAPK phosphorylation and down regulation of the AT1R suggesting that the observed inhibitory effect is mediated through MAPK signaling intermediate(s). Our studies demonstrate for the first time that tannic acid inhibits the AT1R gene expression and illustrate that dietary polyphenols blunt hypertension, in part through inhibition of AT1R. Supported by NIH Grant DK072140

Effect of tea phenolics on iron uptake from different fortificants by Caco-2 cells

Abstract The in vitro effects of tea phenolics on Fe uptake from different fortificants (FeSO4, FeCl3, FeEDTA) by Caco-2 cells were compared. Cell cultures were exposed to catechin, tannic acid, green or black tea solutions, added within Fe-containing solution, or used to pre-treat cell cultures before Fe-exposure. Cell ferritin formation was used as a measure of Fe uptake. Reverse phase chromatography was used to identify specific phenolics in tea solutions, and the Fe-binding catechol and galloyl groups were determined spectrophotometrically. The results showed a positive effect of catechin on Fe uptake only from dissociable Fe sources, and a marked inhibitory effect of tannic acid regardless of the Fe source. Tea phenolics exhibit similar inhibitory patterns on Fe uptake from FeCl3 and FeEDTA solutions; however, the Fe uptake from FeSO4 solutions was significantly less affected. These data improve the understanding of interactions by which tea phenolics affect Fe uptake at the intestinal level.

The inhibitory effect of tannic acid on cytochrome P450 enzymes and NADPH-CYP reductase in rat and human liver microsomes

Tannic acid has been shown to decrease mutagenicity and/or carcinogenicity of several amine derivatives and polycyclic aromatic hydrocarbons in rodents. The purpose of this study was to evaluate the effect of tannic acid on cytochrome P450 (CYP)-catalyzed oxidations using rat liver microsomes (RLM) and human liver microsomes (HLM) as the enzyme sources. In RLM, tannic acid showed a non-selective inhibitory effect on 7-methoxyresorufin O-demethylation (MROD), 7-ethoxyresorufin O-deethylation (EROD), tolbutamide hydroxylation, p-nitrophenol hydroxylation and testosterone 6β-hydroxylation activities with IC 50 values ranged from 14.9 to 27.4 μM. In HLM, tannic acid inhibited EROD, MROD and phenacetin O-deethylation activities with IC 50 values ranged from 5.1 to 7.5 μM, and diclofenac 4-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and testosterone 6β-hydroxylation with IC 50 values ranged from 20 to 77 μM. In baculovirus-insect cell-expressed human CYP 1A1 and 1A2, the IC 50 values of tannic acid for CYP 1A1- and 1A2-catalyzed EROD activities were 23.1 and 2.3 μM, respectively, indicating that tannic acid preferably inhibited the activity of CYP1A2. Tannic acid inhibited human CYP1A2 non-competitively with a Ki value of 4.8 μM. Tannic acid was also found to inhibit NADPH-CYP reductase in RLM and HLM with IC 50 values of 11.8 and 17.4 μM, respectively. These results suggested that the inhibition of CYP enzyme activities by tannic acid may be partially attributed to its inhibition of NADPH-CYP reductase activity.

Inhibitory effect of tannic acid on iron–dextran‐augmented and 7,12‐dimethyl benz(a)anthracene‐initiated skin carcinogenesis

AbstractTannic acid (TA) is naturally occurring polyphenol present in fruits and vegetables. In this study we report that TA inhibits the carcinogenic effect of 7,12‐dimethylbenz(a)anthracene (DMBA) in normal and iron‐overloaded mice skin. Albino Swiss mice were given iron–dextran and pretreated with a single topical application of tannic acid; after 1 h, tumors were initiated by multiple topically application of DMBA. Appearance, number, and percent tumor incidence were recorded. When compared with the control group, the pretreated groups showed a significantly higher inhibition of tumor incidence. The induction of [3H]thymidine incorporation in cutaneous DNA and lipid peroxidation was inhibited in TA‐pertreated animals as compared with the normal control group. Based on this study, we propose that TA significantly inhibits the augmentation potential of iron–dextran. A depletion in lipid peroxidation levels in TA‐pretreated groups indicates that excessive generated oxidants in the mice skin tissues may be quenched by TA and because of the chelation of redox active iron and its faster elimination from the body. In conclusion, our data suggest that TA may be an effective chemopreventive agent and may offer protection against iron mediated skin cancer. J. Trace Elem. Exp. Med. 17:21–29, 2004. © 2004 Wiley‐Liss, Inc.