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Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer.

ABSTRACT: This study aimed to clarify the bioavailability mechanism of theaflavins by using the Caco-2 monolayer in vitro model. Prior to the transport of theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3'-gallate (TF3'G), and theaflavin-3, 3'-digallate (TFDG), we found the cytotoxicity of theaflavins was in the order of TF3'G > TFDG > TF3G > TF, suggesting the galloyl moiety enhances the cytotoxicity of theaflavins. Meantime, the galloyl moiety made theaflavins unstable, with the stability in the order of TF > TFDG > TF3G/TF3'G. Four theaflavins showed poor bioavailability with the P_app values ranging from 0.44 × 10^-7 to 3.64 × 10^-7 cm/s in the absorptive transport. All the theaflavins showed an efflux ratio of over 1.24. And it is further confirmed that P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs) and breast cancer resistance protein (BCRP) were all shown to contribute to the efflux transport of four theaflavins, with P-gp playing the most important role, followed by MRPs and BCRP. Moreover, theaflavins increased the expression of P-gp, MRP1, MPR3, and BCRP while decreased the expression of MRP2 at the transcription and translation levels. Additionally, the gallated theaflavins were degraded into simple theaflavins and gallic acids when transported through Caco-2 monolayers. Overall, the structural instability, efflux transporters, and cell metabolism were all responsible for the low bioavailability of four theaflavins in Caco-2 monolayers.

SUBMITTER: Qu F

PROVIDER: S-EPMC8409943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Theaflavins, polyphenols of black tea, inhibit entry of hepatitis C virus in cell culture.

Project description:The treatment of hepatitis C virus (HCV) infection by combination of direct acting antivirals (DAA), with different mode of action, has made substantial progress in the past few years. However, appearance of resistance and high cost of the therapy is still an obstacle in the achievement of the therapy, more specifically in developing countries. In this context, search for affordable antivirals with new mechanisms of action is still needed. Tea, after water, is the most popular drink worldwide. Polyphenols extracted from green tea have already shown anti-HCV activity as entry inhibitors. Here, three different theaflavins, theaflavin (TF1), theaflavin-3'-monogallate (TF2), and theaflavin-3-3'-digallate (TF3), which are major polyphenols from black tea, were tested against HCV in cell culture. The results showed that all theaflavins inhibit HCV infection in a dose-dependent manner in an early step of infection. Results obtained with HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action. No effect on HCV replication was observed by using HCV replicon. Investigation on the mechanism of action of black tea theaflavins showed that they act directly on the virus particle and are able to inhibit cell-to-cell spread. Combination study with inhibitors most widely used in anti-HCV treatment regimen demonstrated that TF3 exerts additive effect. In conclusion, theaflavins, that are present in high quantity in black tea, are new inhibitors of HCV entry and hold promise for developing in therapeutic arsenal for HCV infection.

| S-EPMC6261387 | biostudies-literature

Simultaneous Determination of Black Tea-Derived Catechins and Theaflavins in Tissues of Tea Consuming Animals Using Ultra-Performance Liquid-Chromatography Tandem Mass Spectrometry.

Project description:The bioavailability, tissue distribution and metabolic fate of the major tea polyphenols, catechins and theaflavins as well as their gallated derivatives are yet to be precisely elucidated on a single identification platform for assessment of their relative bioefficacy in vivo. This is primarily due to the lack of suitable analytical tools for their simultaneous determination especially in an in vivo setting, which continues to constrain the evaluation of their relative health beneficiary potential and therefore prospective therapeutic application. Herein, we report a rapid and sensitive Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) based method for the simultaneous determination of the major catechins and theaflavins in black tea infusions as well as in different vital tissues and body fluids of tea-consuming guinea pigs. This method allowed efficient separation of all polyphenols within seven minutes of chromatographic run and had a lower limit of quantification (LLOQ) of ~5 ng/ml. Using this method, almost all bioactive catechins and theaflavins could be simultaneously detected in the plasma of guinea pigs orally administered 5% black tea for 14 days. Our method could further detect the majority of these polyphenols in the lung and kidney as well as identify the major catechin metabolites in the urine of the tea-consuming animals. Overall, our study presents a novel tool for simultaneous detection and quantitation of both catechins and theaflavins in a single detection platform that could potentially enable precise elucidation of their relative bioavailability and bioefficacy as well as true health beneficiary potential in vivo. Such information would ultimately facilitate the accurate designing of therapeutic strategies utilizing high efficacy formulations of tea polyphenols for effective mitigation of oxidative damage and inflammation in humans as well as prevention of associated diseases.

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Inhibition of pancreatic lipase by black tea theaflavins: Comparative enzymology and in silico modeling studies.

Project description:Few studies have examined the effect of black tea (Camellia sinensis) theaflavins on obesity-related targets. Pancreatic lipase (PL) plays a central role in fat metabolism and is a validated target for weight loss. We compared the inhibitory efficacy of individual theaflavins and explored the underlying mechanism. Theaflavin-3,3'-digallate (TFdiG), theaflavin-3'-gallate, theaflavin-3-gallate, and theaflavin inhibited PL with IC50 of 1.9, 4.2, 3.0, and >10?mol/L. The presence and location of the galloyl ester moiety were essential for inhibitory potency. TFdiG exhibited mixed inhibition with respect to substrate concentration. In silico modeling showed that theaflavins bind to Asn263 and Asp206, which form a pocket adjacent to the active site, and galloyl-containing theaflavins are then predicted to perturb the protonation of His264. These data provide a putative mechanism to explain the anti-obesity effects of tea.

| S-EPMC5228287 | biostudies-literature

Intestinal Absorption of Ergostane and Lanostane Triterpenoids from Antrodia cinnamomea Using Caco-2 Cell Monolayer Model.

Project description:Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5 (25R-antcin H), 6 (25S-antcin H) and 10 (25R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13 (dehydroeburicoic acid) and 14 (eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K (1-6 and 9-11) were absorbed via passive transcellular diffusion, and showed high P AB and P BA values (> 2.5 × 10(-5) cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid (8), 15?-acetyldehydrosulphurenic acid (12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human.

| S-EPMC4607679 | biostudies-other

Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea.

Project description:The aim of this work is to discover the inhibitory mechanism of tea peptides and to analyse the affinities between the peptides and the angiotensin-converting enzyme (ACE) as well as the stability of the complexes using in vitro and in silico methods. Four peptide sequences identified from tea, namely peptides I, II, III, and IV, were used to examine ACE inhibition and kinetics. The half maximal inhibitory concentration (IC50) values of the four peptides were (210.03±18.29), (178.91±5.18), (196.31±2.87), and (121.11±3.38) μmol/L, respectively. The results of Lineweaver-Burk plots showed that peptides I, II, and IV inhibited ACE activity in an uncompetitive manner, which requires the presence of substrate. Peptide III inhibited ACE in a non-competitive manner, for which the presence of substrate is not necessary. The docking simulations showed that the four peptides did not bind to the active sites of ACE, indicating that the four peptides are allosteric inhibitors. The binding free energies calculated from molecular dynamic (MD) simulation were -72.47, -42.20, -52.10, and -67.14 kcal/mol (1 kcal=4.186 kJ), respectively. The lower IC50 value of peptide IV may be attributed to its stability when docking with ACE and changes in the flexibility and unfolding of ACE. These four bioactive peptides with ACE inhibitory ability can be incorporated into novel functional ingredients of black tea.

| S-EPMC8284085 | biostudies-literature

Effect-Directed Profiling of Powdered Tea Extracts for Catechins, Theaflavins, Flavonols and Caffeine.

Project description:The antioxidative activity of Camelia sinensis tea and especially powdered tea extracts on the market, among others used as added value in functional foods, can considerably vary due to not only natural variance, but also adulteration and falsification. Thus, an effect-directed profiling was developed to prove the functional effects or health-promoting claims. It took 3-12 min per sample, depending on the assay incubation time, for 21 separations in parallel. Used as a fast product quality control, it can detect known and unknown bioactive compounds. Twenty tea extracts and a reference mixture of 11-bioactive compounds were investigated in parallel under the same chromatographic conditions by a newly developed reversed phase high-performance thin-layer chromatographic method. In eight planar on-surface assays, effect-directed tea profiles were revealed. Catechins and theaflavins turned out to be not only highly active, but also multi-potent compounds, able to act in a broad range of metabolic pathways. The flavan-3-ols acted as radical scavengers (DPPH? assay), antibacterials against Gram-positive Bacillus subtilis bacteria, and inhibitors of tyrosinase, ?-glucosidase, ?-glucosidase, and acetylcholinesterase. Further effects against Gram-negative Aliivibrio fischeri bacteria and ?-glucuronidase were assigned to other components in the powdered tea extracts. According to their specifications, the activity responses of the powdered tea extracts were higher than in mere leaf extracts of green, white and black tea. The multi-imaging and effect-directed profiling was not only able to identify known functional food ingredients, but also to detect unknown bioactive compounds (including bioactive contaminants, residues or adulterations).

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| S-EPMC8240975 | biostudies-literature

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Project description:Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI) delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient (Papp) values of BFL in free or BPDI form were over 1.0 × 10-6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the Papp values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL.

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