Food Reviews International

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Insight into Tea Flavonoids: Composition and

Chemistry

Hua-Feng He, Kang Wei, Junfeng Yin & Yang Ye

To cite this article: Hua-Feng He, Kang Wei, Junfeng Yin & Yang Ye (2020): Insight
into Tea Flavonoids: Composition and Chemistry, Food Reviews International, DOI:
10.1080/87559129.2020.1721530

To link to this article: https://doi.org/10.1080/87559129.2020.1721530

Published online: 23 Feb 2020.

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FOOD REVIEWS INTERNATIONAL
https://doi.org/10.1080/87559129.2020.1721530

Insight into Tea Flavonoids: Composition and Chemistry

Hua-Feng He, Kang Wei, Junfeng Yin, and Yang Ye
Tea Research Institute, Chinese Academy of Agricultural Sciences, HangZhou, China

ABSTRACT KEYWORDS
Tea is a popular beverage over the world for centuries. It is well Flavonoids; tea; category;
known that tea has various health benefits such as anti-tumor, anti- constituents
oxidation, antiphlogosis as well as prevention of cardiovascular dis-
ease, etc. Phytochemicals in tea leaves are the contributors to the
excellent bioactivities of tea. Therein, flavonoids were the most
potent compounds. Thousands of pioneer work had been made to
investigate the potential of tea flavonoids as candidates. This review
sorted the literature published in recent 5 years. In view of processing
method, basic manufacturing procedures for the traditional types of
tea were described. Research progress and functionality of tea flavo-
noids were discussed according to chemical structures. Fruitful
research results about tea flavonoids were summarized and refined,
and in-depth cognition of tea flavonoids would be obtained. We also
point out the forthcoming orientation for the study on tea flavonoids
based on our own understanding and consideration.

Introduction
Phytochemicals, abundantly present in nature, are potent candidates for new drugs, due to
their high accessibility, excellent bioactivities, good biocompatibility, low cost and relatively
low toxicity compared with synthetic drugs. Thereinto, flavonoids with the characteristic
structure consisting of two phenyl rings (A and B) and a pyranoid ring C are widely present in
plants. Flavonoids are classified into flavanols, flavonols, anthocyanidins, flavones, flavanones,
isoflavones, based on the position of ring B as well as the oxidative degree and cyclic state of
ring C. Multiple bioactive hydroxyl groups in the molecular structures of flavonoids make
them promising natural antioxidants for both food and human body.
Generally, linked with oxhydryl, methoxyl and glucoside, flavonoids showed prominent
activities in anti-inflammation, antimicrobial, anti-oxidation, anti-tumor and so on.
Flavonoids exert multiple benefits in the prevention of commonly encountered diseases,
e.g., periodontics disease.[1] As a natural therapeutic adjuvant for cancer, flavonoids play
a role in maintaining the cellular redox balance against canceration.[2] In terms of
attenuating neurodegeneration, Parkinson’s disease (PD),[3] Alzheimer’s disease (AD),
etc., flavonoids possessed the potential to down-regulate the nitric oxide (NO) production,
suppress lipid peroxidation, inhibit inflammatory mediators, and activate antioxidant
enzymes.[4] Recently, flavonoids were reported to have the potential of regulating non-
shivering thermogenesis, which would be conducive to prevent abnormal fat
accumulation.[5] Structure activity relationship (SAR) revealed that mixed-type inhibitory

CONTACT Kang Wei weikang@tricaas.com; Yang Ye yeyang@tricaas.com Tea Research Institute, Chinese
Academy of Agricultural Sciences, HangZhou 310008, China
© 2020 Taylor & Francis
2 H.-F. HE ET AL.

capacity of flavonoids and their congener was related with the number and position of
hydroxyl groups in the structures of flavonoids.[6] Binding of flavonoids to the active site
of α-amylase resulted in the inhibition on the enzymatic activity.[7]
Tea, originated in the Yunnan-Guizhou Plateau of China, was regarded to possess
excellent free radical scavenging capacity and multiple physiological functions owing to
the high levels of flavonoids in its leaves. As one of the most popular beverages all over the
world, second only to water, tea is the optimal source of dietary flavonoids that cannot be
synthesized by human body.[8] On the other hand, tea attracts substantial research interest
as nutraceuticals owing to their multi-benefits on human health problems.[9–14] In nature,
flavonoids present in tea paid most of the bill for these distinct bioactivities. Herein,
constituent function as well as perspective of flavonoids distributed in tea need
a systematic review in order to achieve more extensive recognition and new insight for
the utilization of tea flavonoids.

Tea flavonoids: chemical structure and their function

It is well known daily drinking of tea would be benefit for human health. Negative relationship
was showed between dietary intake of tea and the prevalence of some chronic diseases,
diabetes, for instance.[15] Substantially, intake of phytochemicals, such as catechins,
L-theanine, caffeine, etc., lay the chemical foundation for the advantage, and among them,
flavonoids were most critical. These phenolic compounds contained in tea participated in the
metabolism of human body. Interacted with gut microbiota, new active metabolites would be
generated from tea flavonoids, which possess potential beneficial effects.[16] Participated in the
regulation of cytochrome P450 (CYP) and phase II enzymes, tea flavonoids also exhibited
xenobiotic effects.[17] In the prevention and treatment of obesity, tea flavonoids constitute the
oldest and most extensive form of alternative treatments.[18]
Based on the skeleton of molecule, flavonoids distributed in tea leaves were primarily
present in forms of flavanols, flavonols, and anthocyanins, as well as bioflavonoids,
theaflavins (TFs).[19] Limit to the content in tea and actual role, research about tea
resourceful flavonoids concentrated mainly on catechins, TFs, and so on such several
characteristic molecules. Herein, pioneer research would be combed sequentially accord-
ing to the popularity degree in the field of research about tea.

Catechins
Catechins were regarded as the pharmacodynamic material basis of tea, which accounts
for 60 ~ 80% of total tea polyphenols. Therefore, catechin was the most often mentioned
and representative member. Typically, being a member of flavan-3-ols family, 3-oxhydryl
substituted chroman (ring A and C) and aryl at the 2-poision (ring B) were existed in the
skeleton of catechins (as shown in Fig. 1). [20,21] As the iconic component, most attention
of tea researchers were paid to catechins.[22] Research on regulation of genetic expression,
secondary metabolism, functional application as well as clinical drug evaluation about
catechins has been hotspot for decades. Difference in the substituted groups and stereo-
chemistry, 16 isomers were present in nature theoretically. Actually, EC, EGC, ECG and
Epigallocatechin gallate (EGCG) were the most common catechins isolated from tea.
Particularly, EGCG was dominant, content of which could be up to 50% of the flavanols
 FOOD REVIEWS INTERNATIONAL 3

Figure 1. Structure of catechins.

in tea. As a result, research on the bioactivity of catechins was carried out focusing on
EGCG mostly. According to literatures, antioxidant ability was directly bound up with
hydroxyl group. Compared with the other catechins, with the presence of up to eight-
hydroxy groups in its skeleton, EGCG possessed the most outstanding potential for
antioxidation and free radical scavenging.[23]
Besides the direct affection on organoleptic quality of tea,[24] catechins, especially EGCG,
showed excellent activities on human health coupled with other molecules in tea, L-theanine,
caffeine, etc.[25] Daily drinking of tea, the absorption of catechins in essence, exhibited
antiobesity effect in a certain extent.[10,26] Long-term intake of catechins displayed therapeutic
effect for chronic disease. For instance, in vitro and animal trial verified EGC possessed blood
anticoagulation and antiplatelet activity.[27] As one of micronutrients, catechins could be
seemed to be cardioprotective.[28] Also, in prevention of cancer, human prostate cancer (PCa)
in particular, catechins exerted ideal antagonism clinically.[29] Meanwhile, catechins would be
promising molecule for neurodegenerative disorders, PD, AD, etc.[30,31] By the way, through
suppressing the activity of P450, catechins participated in the liver metabolism and detox-
ification process.[32] Epidemiologic study demonstrated catechins would be a benefit to
prevention of influenza infection.[33] However, daily intake dose of catechins should be
cautious. For instance, the suggested dose of EGCG as a food supplement was under
800 mg/day released by the European Food Safety Authority (EFSA).[34]

Theaflavins
Isolated from tea by Roberts firstly, TFs were the first one proved to be pharmacological active
explicitly. As a bipolymer of catechin, TFs consist of two chromanes and a benzotropolone
skeleton, which oxidized from B ring of catechins (as shown in Fig. 2). TFs exert comparable
or even better pharmacological effect as catechins, in terms of antioxidation, cancer adjuvant
therapy, anti-obesity effect, etc.[35] In addition to these conventional efficacies, TFs showed
remarkable activates on anti-mutagenicity and hypolipidemic.[36] Through depressing the
automatic phosphorylation of proteins, signalling pathway of transcription factor was blacked.
TFs play defending roles in preventing DNA damage.
Besides, for prevention and regulation of mental disorders, such as anxiety disorder and
depression, consumption of TFs is associated with the increase of dopamine (DA) turn-
over in the frontal cortex. In other words, TFs could induce anxiolytic effects via activation
of the dopaminergic system.[37] TFs were reported to have skin rejuvenation effects
4 H.-F. HE ET AL.

Figure 2. Structure of theaflavins.

through induction of the subcutaneous adipogenesis.[38] Silico molecular docking and

molecular simulation studies indicated TF as well as EGCG exhibited a high XP dock
score, which could be screened as candidates for gp120-CD4 binding inhibitor.[39]

Anthocyanins
Typically, anthocyanins were taken into consideration for investigation when purple tea
was mentioned.[40] Resourceful utilization of them was mainly in other plants, blueberry,
cabbage, black bean and so on. Anthocyanins, present in petal, contribute to the multi-
colour of flowers that are pH-dependent. From a chemical perspective, the molecular
structure of anthocyanins containing hydroxyl substituted six-membered ring oxocarbe-
nium ion enables its sensitivity to pH value.
In tea, cyanidin (Cy), pelargonidin (Pg), delphinidin (Dp) were familiar (showed in Fig. 3).
Obviously, the difference was embodied in the number of hydroxyl groups in the B ring.
Genetically, CsMYB75 coupling with CsGSTF1 were pointed to be associated with anthocya-
nin hyperaccumulation in purple tea, Zijuan, Ziyan, etc.[41] Taking tea as substrate, antho-
cyanin could be produced by Lactococcus lactis in cell factories to afford the bio-utilization.[42]
Owing to the presence of anthocyanin, pH-sensitive and antioxidant packaging films could be
prepared for food packaging.[43] Incubated with Dulbecco’s modified Eagle’s medium
(DMEM), stability of 10 of the most common anthocyanins was evaluated.[44] And the result
showed glycosylation as well as methylation would be benefit for enhancement of stability of
anthocyanins.

Leucoanthocyanidins
As shown in Fig. 3, with the extra oxhydryl located at the 4-position on ring C, leucoantho-
cyanidins could be seemed as hydroxylated derivative of catechins. By the same token, the
stabilities of leucoanthocyanidins were significantly lower than those of catechins. Under
oxidative condition, the colourless leucoanthocyanidins are transformed to coloured matter,
such as anthocyanidins. Nevertheless, Zhang et al. demonstrated no cyanidin was produced
 FOOD REVIEWS INTERNATIONAL 5

Figure 3. Chemical structure of primary flavonoids distributed in tea.

with the natural cis isomer of leucocyanidin under the catalysis of anthocyanidin synthase
from Vitis vinifera (VvANS). In other words, other substrate was needed for the in vivo
formation of anthocyanidins.[45]
Research about leucoanthocyanidins in tea was most focused on expression of relative
gene as well as the reductase on the synthesis of catechins. Leucoanthocyanidin reductase
(LAR) was pronounced closely related to the biosynthesis as well as epimerization of
catechins.[46] In prevention of nonalcoholic fatty liver disease (NAFLD), there is a special
place for leucoanthocyanidin.[47]

Flavonols
There are three major types of flavonols in tea leaves, such as kaempferol, quercetin and
myricetin with different numbers of hydroxyl groups on the ring B (shown as in Fig. 3).
Flavonols are mainly present in the forms of glycosides in tea leaves, and glycosylation
level of flavonol could be the indicator for the discrimination of the processing suitability
of tea varieties.[48] Coincidentally, high levels of flavonol were found in onions, citrus
fruits, berries, asparagus and leafy vegetables.[49] Even so, beneficial effect exerted by
flavonols may be superior to flavanols in tea.[50] Due to diverse physiological health
effects, quercetin was developed as regulator for multiple dysfunction.[51,52] Regulating
iron metabolism genes, quercetin could inhibit duodenal non-haem iron absorption in
6 H.-F. HE ET AL.

systemic iron metabolism, which could lead to development of new effective ways of
preventing and treating iron-deficiency anaemia.[53] Simultaneous encapsulation of EGCG
with quercetin could enhance their effectiveness and stability.[54] Kaempferol might dis-
play an anti-obesity effect through inhibiting adipogenesis and increasing lipolysis.[55] An
endothelium-independent vasorelaxation could be induced by kaempferol.[56]

Other flavonoids in tea

Generally linked with glycosyl moiety, flavonoids consist of a variety of derivatives. For
example, dimerized from catechins, theasinensins (TSs) could be seemed as a competitor
of TFs in the process of enzymatic oxidation during tea processing.[57] Due to the
comparable biological activity to TFs, more and more attention was paid to TSs.[58]
Administration of TSs was associated with hepatoprotective effect.[59]
Other flavonoids like apigenin and patuletin were trace-level in tea, which were rarely
studied in tea research area. Tea was not the traditional superior resources of these
compounds. Hence, research about them would not be described here.

Perspective for utilization of tea flavonoids

There are diverse flavonoids existed naturally in tea, which offered a wealth of possibilities
for utilization in pharmacology. Acting as scavengers for free radicals, tea flavonoids
demonstrated potential pharmaceutical activities, particularly in cardioprotective
effects.[60] Medicinal efficacies of tea flavonoids as antibacterial, hepatoprotective, anti-
inflammatory, anticancer, and antiviral agents had been well established. On the other
hand, with the development of instrument and technology, more flavonoids with new
structure and activity would be isolated from tea. Different flavonoids possess their own
physical, chemical, and physiological properties. However, natural compounds cannot be
a panacea, especially when taking differences between biological settings in health and
disease into account. First of all, bioavailability of tea flavonoids should be enhanced.
Meanwhile, factors that had impact on the metabolic accumulation in tea remained to be
further clarified.

Modification of the chemical structure of tea flavonoids

Regular intake, simply as drinking of tea daily, would be the ideal acquisition of phyto-
chemical. Considering the low natural contents as well as impenetrable absorption, the
orally intake dose of tea flavonoids, mainly through drinking of tea, could reach the
systemic circulation at trace level. As a result, opportune modifications of tea flavonoids
were desirable to enhance their bioavailability.[6] Cai[61] and co-worker reviewed the
advances in bioavailability studies involving absorption and metabolic biotransformation
of tea catechins. Techniques, nanostructure-based drug delivery system, molecular mod-
ification, co-administration of catechins with other bio-actives, etc., introduction of which
would be benefit for improving the bioavailability of tea catechins, were also discussed.
Coincidentally, Liu, et al. reported grafting of flavonoids onto polysaccharides significantly
improve the antioxidant, antimicrobial, antitumor, hepatoprotective and enzyme inhibi-
tion properties of polysaccharides.[62] Conjugated with catechin, ovotransferrin (OTF)
 FOOD REVIEWS INTERNATIONAL 7

showed improved antioxidant activity.[63] Both of these researches directed tea flavonoids
can be developed as adjuvant for nutraceutical delivery.
Still and all, purification of absolute structural tea flavonoids and verification of
pharmacokinetic study was hysteretic. Stability of the polyhydroxyl structure of tea
flavonoids in vivo, especially in the stomach acid environment, should be taken into
account. As complementary and alternative medicines, compatibility and synergistic effect
of tea flavonoids deserves to be carefully weighed. To more effectively target, there is still
a long way to go before therapeutic use of tea flavonoids.

Isolation of new novel structured tea flavonoids

Chemically, flavonoids are benzo-γ-pyrone derivatives that most present in forms of glyco-
sides when mentioned in tea. Mediated under glucoside hydrolase, dissociation of tea flavo-
noids occurred throughout the process of tea plant growth and tea processing. With 1000
varieties of tea trees as well as characteristic processing technology, both of which could exert
influence on the constituent of flavonoids, separation and screening for new structural
flavonoids from tea appears especially important. Particularly, development of analytical
instrument and technology in recent decades endowed more measures for exploration of
tea flavonoids. By means of nuclear magnetic resonance (NMR) and high-performance liquid
chromatography with diode array detection and electrospray ionization mass spectrometry
(HPLC-DAD–ESI/MS) analysis, marker compounds of Chinese dark tea, 8-C N-ethyl-2pyr-
rolidinone substituted flavan-3-ols were specified.[64] Cheng[65] and Guo[66] identified novel
structural flavonoids from Xi-Gui and Pu-erh tea separately. Li et al. isolated four novel
flavoalkaloids (−)-6-(5”’-S)-N-ethyl-2-pyrrolidinone-epigallocatechin-O-gallate, (−)-6-(5”’-
R)-N-ethyl-2-pyrrolidinone-epigallocatechin-O-gallate, and (−)-8-N-ethyl-2-pyrrolidinone-
epigallocatechin-O-gallate from white tea.[67] From fuzhuan brick tea, one kind of dark tea,
two quercetin acylglycosides and two kaempferol acylglycosides were isolated.[68] Also, the
metabolomics research would be another topic for detail understanding of the metabolic
mechanism of tea flavonoids.[69,70] In addition, higher extraction efficiency as well as solvents
with more environmental friendliness would be the pursuit for green extraction of tea
flavonoids.

Affection on the biosynthesis of tea flavonoids

In term of affection to the metabolism of flavonoids in tea, nutrition and cultivation were
indispensable. Phosphate[71], nitrogen,[72] also other elements essential in growth of tea
trees would be influential in the accumulation of tea flavonoids. When it turns to genetic
affection on biosynthesis of flavonoids, Zhu and co-worker investigated the regulatory
function of alternative splicing (AS).[73] Wang et al. declared two MYB transcription
factors (CsMYB2 and CsMYB26) were regulators of flavonoid biosynthesis in plants.[74]
Simultaneously, effect of illumination on the accumulation of flavonoids in tea was
noteworthy. Regulating on the genic expression, blue and green light could stimulate
the formation of anthocyanins, catechins and procyanidin differently.[75] Furthermore,
interplay between flavonoids and other pigments in the biosynthesis in tea trees is still
unclear.
8 H.-F. HE ET AL.

Conclusion
In a word, as one of the most favourable beverages, tea would be the rich source of
flavonoids for daily intake. Drawn nourishment from pioneer research, structure elucida-
tion of tea flavonoids, catechins, TFs, anthocyanins, leucoanthocyanidins, flavonols and
other non-primary flavonoids was released sequentially. Interacting with standard che-
motherapeutics synergistically, tea flavonoids are becoming complementary and alterna-
tive medicines. Thereby, modification of tea flavonoids for higher bioavailability, isolation
of more new structural tea flavonoids and explication of factors that affect the accumula-
tion of flavonoids in tea plant would be the objective for the upcoming orientation of
study on tea flavonoids. All these aspirations would be inducement to lucubrate tea
resourceful flavonoids.

Funding
This work was financially supported by the Central Public-interest Scientific Institution Basal
Research Fund [No.1610212016020] and the Science and Technology Innovation Program of the
Chinese Academy of Agricultural Sciences [CAAS-ASTIP-TRICAAS].

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