Increased evidence has expanded the role of green tea from a traditional beverage to a source of bioactive ingredients with many health benefits. Green tea is rich in catechins comprised of more than eight polyphenolic compounds. According to different sources, the most abundant catechins in tea are (−)-epigallocatechin gallate (EGCG) and (−)-epigallocatechin (EGC) [1
]. In recent years, EGCG has attracted significant research interest due to its beneficial health effects including antioxidation [3
], anti-diabetes [4
], anti-inflammation [5
] and anti-tumorigenesis activity [8
]. Therefore, EGCG has recently gained the attention of scientists for implementation as a therapeutic alternative for treating some diseases.
There have been many in vitro studies showing that EGCG possesses antioxidant properties and exhibits favorable effects on gene expression, signal transduction and other cell functions [9
]. Numerous potential mechanisms have been proposed to explain the healthy benefits of tea catechins, including improving antioxidative activity, suppressing adipocyte differentiation, regulating the tumor-suppressor microRNAs, inhibiting hepatocyte growth factor receptor activity, inhibiting Iκb kinase activity, etc. [3
]. In vitro studies showed that the effective concentrations of EGCG ranged from 1 to 100 μmol/L. However, the peakplasma levels of tea catechins were usually in the sub-or low-micromolarrange in human subjects or animals following oraladministration of green tea catechins [14
], which was lower than the effective concentration of in vitro tests. Therefore, the therapeutic effect is limited, owing to poor stability in the gastrointestinal tract and limited membrane permeability across the intestine [16
]. Their therapeutic potential is limited by its poor systemic absorption following oral administration, including low absorption, poor pharmacokinetics and bioavailability, scarce biodistribution, first-pass metabolism, trivial penetration and low accumulation in the related tissues of the body, or low targeting efficacy. The inconsistency between catechins’ superior in vitro biological activity and low absorption in in vivo studies can also be attributed to its low stability, which lead to the formation of degradation products and pro-oxidant molecules [19
]. Catechins are unstable under physiologic conditions and they could be rapidly degraded or metabolized through interactions with the hydroxyl groups on the phenol rings [19
]. Even if administered intravenously, catechins were partially degraded before reaching the target tissues [20
]. EGCG needs to work at a relatively high concentration to target related molecules and to affect disease-related cellular processes [9
]. It is believed that taking green tea polyphenol products in amounts equivalent to the EGCG content in 8–16 cups of green tea daily may mitigate the poor bioavailability of EGCG [22
]. The systemic availability of EGCG increased at higher doses, possibly due to saturable pre-systemic elimination of orally administered green tea polyphenols (GTPs) [23
]. However, it is obviously not a good idea to use excessive dose of catechins for improving effectiveness. Studies from experimental animals and epidemiological surveys have shown that GTPs have a dose-dependent toxicology [24
]. Tea polyphenols are antioxidants, but they can also generate reactive oxygen species (ROS). It was observed that moderate doses of tea polyphenols induced finite amount of lower level of ROS which may also activates nuclear factor erythroid 2-related factor 2 (Nrf2) to activate antioxidant and detoxifying enzymes, and then attenuate oxidative stress, whilst excessive amounts of GTPs probably induced a pro-oxidant effect, resulting in induced toxicity effect [9
The present paper comprehensively reviews the mechanisms leading to low absorption, poor permeability and less stability of tea catechins and also describes the potential for improving the bioavailability of tea catechins through new techniques such as nanoparticle-based delivery systems, structurally modified molecule of catechins, co-administration with other drugs or bioactives. Furthermore, the challenges and future research directions are also discussed.
To collect the related references, computerized systematic literature searches were conducted inWeb of Science and Google Scholar databases to retrieve the pertinent studies and reviews. The search keywords used were tea catechins or tea polyphenolsor epigallocatechin gallate (EGCG) in combination with the terms absorption, bioavailability, metabolism, or nanoparticles, chitosan, prodrugs, peracetylate, and synergistic as well as the terms improvementand enhancement. The papers published in the English languagewere exclusively evaluated. No other limitations were applied. The literatures were combed and divided into four main categories: (a) pharmacokinetics of tea catechins, (b) drug delivery system, (c) molecular modification, and (d) synergistic effect with other drugs. Thus, the review is structured. First, into a discussion on the bioavailability of catechins, and then, to provide more thorough insights into the way and mechanism to improve.