Influence of Delivery Systems on the Absorption and Transport of Theaflavins in Caco-2 Cell Model

Abstract

Abstract: Theaflavins (TFs), as functional polyphenols in black tea, exhibit extremely low bioavailability, which severely limits their application in functional foods. Previous studies have shown that water-in-oil (W/O) emulsions can significantly improve the bioaccessibility of TFs. Building on this, the present study investigated the effects of digested aqueous solutions, oil-water mixtures and water-in-oil emulsions on the cellular uptake and cellular transport of TFs based on the Caco-2 cell model. The results demonstrated that the cellular uptake rate of TFs in the W/O emulsion reached 11.02%, which was 3.13 times and 2.50 times higher than that of the aqueous solution (3.52%) and the oil-water mixture (4.41%), respectively. After 4 h of incubation, TF, TF3G, TF3'G, and TFDG from the emulsion were all taken up by the cells, with uptake rates of 5.83%, 1.36%, 2.63%, and 1.21%, respectively. In contrast, only TF was detected in the oil-water mixture and aqueous solution groups. The cellular secretion rate assay revealed that, the secretion rates of TFs in the oil-water mixture and aqueous solution increased gradually within the 1 to 4 h,whereas the W/O emulsion exhibited a linear increase. After 4 h of incubation, the cellular secretion rate of TFs in the W/O emulsion reached 28.72%, which was 3.6 times and 2.5 times higher than that of the aqueous solution and the oil-water mixture, respectively. Only two monomers, TF and TF3G, were detected in the secretion from the aqueous solution group, whereas all four TFs monomers were identified in both the emulsion and oil-water mixture groups. The secretion rates of TF, TF3G, TF3'G, and TFDG from the emulsion were 16.32%, 2.15%, 3.97%, and 6.28%, respectively, corresponding to 2.39-fold, 1.90-fold, 1.78-fold, and 4.49-fold increases compared to the oil-water mixture. The bioavailability of TFs in the W/O emulsion was 22.95%, representing an 11.3-fold and 4.4-fold enhancement compared to the aqueous solution and oil-water mixture, respectively. This study demonstrates that W/O emulsion significantly improves both the cellular absorption and bioavailability of TFs, providing an important theoretical foundation for their application in the functional food industry.

Key words: Water-in-oil emulsion, Theaflavins, Caco-2 cell model, Bioavailability

CLC Number:

TS201.4

Yu-Ting LU larkin liu. Influence of Delivery Systems on the Absorption and Transport of Theaflavins in Caco-2 Cell Model[J]. FOOD SCIENCE.

References

[1]SANG S, LAMBERT J D, TIAN S, et al.Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and cytotoxic activities[J].Bioorganic & medicinal chemistry, 2004, 12(2):459-67
[2]SHARMA V, RAO L J M.A Thought on the Biological Activities of Black Tea[J].Critical Reviews in Food Science and Nutrition, 2009, 49(5):379-404
[3]BHUYAN L P, BORAH P, SABHAPONDIT S, et al.Spatial variability of theaflavins and thearubigins fractions and their impact on black tea quality[J].Journal of Food Science and Technology-Mysore, 2015, 52(12):7984-93
[4]ITOH N, KUROKAWA J, ISOGAI Y, et al.Functional Characterization of Epitheaflagallin 3-O-Gallate Generated in Laccase-Treated Green Tea Extracts in the Presence of Gallic Acid[J].Journal of Agricultural and Food Chemistry, 2017, 65(48):10473-81
[5]屠幼英, 杨子银, 东方.红茶中多酚类物质的抗氧化机制及其构效关系 [J]. 中草药, 2007, (10): 1581-5.
[6]SHI M, LU Y T, WU J L, et al.Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome [J]. International Journal of Molecular Sciences, 2022, 23(14).[J].International Journal of Molecular Sciences,, , :-
[7]MULDER T P, VAN PLATERINK C J, WIJNAND SCHUYL P J, et al.Analysis of theaflavins in biological fluids using liquid chromatography-electrospray mass spectrometry[J].Journal of chromatography B, Biomedical sciences and applications, 2001, 760(2):271-9
[8]李光华.口服药物吸收的研究进展[J].天津药学, 2014, 26(02):69-71
[9]HB A, MB B, CT A, et al.Encapsulation of probiotics in whey protein isolate and modified huauzontle' s starch: An approach to avoid fermentation and stabilize polyphenol compounds in a ready-to-drink probiotic green tea - ScienceDirect [J]. LWT, 124:109031.
[10]YIN Z Y, ZHENG T, HO C T, et al.Improving the stability and bioavailability of tea polyphenols by encapsulations: a review[J].Food Science and Human Wellness, 2022, 11(3):537-556
[11]YU X, CAI X H, LI S, et al.Studies on the interactions of theaflavin-3, 3 ' -digallate with bovine serum albumin: Multi-spectroscopic analysis and molecular docking [J]. Food Chemistry, 2022, 366.
[12]YE Q, LI T, LI J, et al.Development and evaluation of tea polyphenols loaded water in oil emulsion with zein as stabilizer[J].Journal of Drug Delivery Science and Technology, 2020, 56(5):101528-
[13]HU J, YANG J, GUO H, et al.Effect of Theaflavin on Inflammatory and Remolding of Airway in the Asthma Mice[J].Journal of Biomaterials and Tissue Engineering, 2021, 11(6):1091-8
[14]DING Y, ZOU L, LU C, et al.In situ enzymatic synthesis and purification of theaflavin-3,3 '-digallate monomer and incorporation into nanoliposome[J].International Journal of Food Science and Technology, 2018, 53(11):2552-9
[15]SRIVASTAVA A K, BHATNAGAR P, SINGH M, et al.Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage [J]. International Journal of Nanomedicine, 2013, 8: 1451-62.
[16]JIANG Y K, ZHENG T, JIN W P, et al.Enhancing Intestinal Permeability of Theaflavin-3,3 '-digallate by Chitosan-Caseinophosphopeptides Nanocomplexes[J].Journal of Agricultural and Food Chemistry, 2022, 70(6):2029-41
[17]LU Y T, WU Y J, LIU Y J, et al.Stability and gastrointestinal digestion behaviour of theaflavins encapsulated in W/O Pickering emulsions [J]. Lwt-Food Science and Technology, 2024, 207.
[18]YEE S.In vitro permeability across caco-2 cells can predict in vivo absorption in man - fact or mythpdf[J].Pharmaceutical Research (New York), 1997, 14(6):763-6
[19]谢艳兰, 郭昊蔚, 郑羡慕.细胞模型在茶叶生物活性成分研究中的应用[J].茶叶科学, 2012, 32(6):9-
[20]OJEDA-SERNA I E, ROCHA-GUZMAN N E, GALLEGOS-INFANTE J A, et al.Water-in-oil organogel based emulsions as a tool for increasing bioaccessibility and cell permeability of poorly water-soluble nutraceuticals[J].Food Research International, 2019, 120(JUN.):415-24
[21]LIANG Q, CHALAMAIAH M, REN X, et al.Identification of New Anti-inflammatory Peptides from Zein Hydrolysate after Simulated Gastrointestinal Digestion and Transport in Caco-2 Cells[J].Journal of agricultural and food chemistry, 2018, 66(5):1114-20
[22]BHUSHANI J A, KURREY N K, ANANDHARAMAKRISHNAN C.Nanoencapsulation of green tea catechins by electrospraying technique and its effect on controlled release and in-vitro permeability[J].Journal of Food Engineering, 2017, 199(APR.):82-92
[23]MA J J, HUANG X N, YIN S W, et al.Bioavailability of quercetin in zein-based colloidal particles-stabilized pickering emulsions investigated by the in vitro digestion coupled with caco-2 cell monolayer model [J]. Food Chemistry, 2021, (7): 130152.
[24]LUO Y, TENG Z, WANG T T Y, et al.Cellular Uptake and Transport of Zein Nanoparticles: Effects of Sodium Caseinate[J].Journal of Agricultural & Food Chemistry, 2013, 61(31):7621-9
[25]YEE S.In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth[J].Pharmaceutical research, 1997, 14(6):763-6
[26]SHAN Z, NISAR M F, LI M, et al.Theaflavin Chemistry and Its Health Benefits [J]. Oxidative medicine and cellular longevity, 2021, 2021: 6256618-.
[27]SKOTNICKA M, CHOROSTOWSKA-WYNIMKO J, JANKUN J, et al.The black tea bioactivity: an overview[J].Central European Journal of Immunology, 2011, 36(4):284-92
[28]VERSTRAETEN S V, KEEN C L, SCHMITZ H H, et al.Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and disruption of the bilayer structure[J].Free Radical Biology & Medicine, 2003, 34(1):84-92
[29]REIS A, SOARES S, SOUSA C F, et al.Interaction of polyphenols with model membranes: Putative implications to mouthfeel perception [J]. Biochim Biophys Acta Biomembr, 2020, (2).
[30]QU F, AI Z, LIU S, et al.Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer[J].Drug Delivery, 2021, 28(1):1737-1747
[31]HO C K.Tea polyphenols : absorption, bioavailability and potential toxicity [J]. CAB Reviews Perspectives in Agriculture Veterinary Science Nutrition and Natural Resources, 2017, 12(2).
[32]MUJTABA, DOU, Q.P. Black tea polyphenols inhibit tumor proteasome activity[J].In Vivo: International Journal of In Vivo Research, 2012, 26(2):197-202
[33]LIU Y, XIA H, GUO S, et al.Development and characterization of a novel naturally occurring pentacyclic triterpene self-stabilized pickering emulsion [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2022, 634.
[34]YA LUN S, LAI KWOK L, YU H, et al.Stability of tea theaflavins and catechins[J].Food Chemistry, 2003, 83(2):189-195
[35]HU Y Y, MA C G, ZHOU T L, et al.Enzymatic synthesis of hydrophilic phytosterol polyol esters and assessment of their bioaccessibility and uptake using an in vitro digestion/Caco-2 cell model [J]. Food Chemistry, 2022, (Feb.15): 370.[J].Food Chemistry, , :-
[36]QU F F, AI Z Y, LIU S Y, et al.Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer[J].Drug Delivery, 2021, 28(1):1737-47
[37]CHENG X H, XIONG Y Q.Absorption and transport mechanism of ursolic acid across Caco-2 monolayer model[J].Chinese Pharmacological Bulletin, 2009, 25(8):11189-