Tea (Camellia sinensis): A Review of Nutritional Composition, Potential Applications, and Omics Research

Abstract

Tea (Camellia sinensis) is the world’s most widely consumed non-alcoholic beverage with essential economic and health benefits since it is an excellent source of polyphenols, catechins, amino acids, flavonoids, carotenoids, vitamins, and polysaccharides. The aim of this review is to summarize the main secondary metabolites in tea plants, and the content and distribution of these compounds in six different types of tea and different organs of tea plant were further investigated. The application of these secondary metabolites on food processing, cosmetics industry, and pharmaceutical industry was reviewed in this study. With the rapid advancements in biotechnology and sequencing technology, omics analyses, including genome, transcriptome, and metabolome, were widely used to detect the main secondary metabolites and their molecular regulatory mechanisms in tea plants. Numerous functional genes and regulatory factors have been discovered, studied, and applied to improve tea plants. Research advances, including secondary metabolites, applications, omics research, and functional gene mining, are comprehensively reviewed here. Further exploration and application trends are briefly described. This review provides a reference for basic and applied research on tea plants.

1. Introduction

Tea (Camellia sinensis), belonging to the Theaceae family, was extensively cultivated in Asian, African, Latin American, and Oceanian countries [1,2], which was believed to originate from northeast India, north Myanmar, and southwest China [3,4]. Tea trees are generally divided into three types: shrubs, arbors, and minor arbors. Wild tea trees can reach even 10 m high, and cultivated tea trees are short because they are pruned. The white flowers with a diameter of 4 cm occur singly or pairs, and they contain five sepals and five–nine petals for each flower. The brownish-green fruits contain one–four spherical or flattened seeds. The leaf size is varied in different tea varieties, ranging in length from 3.8 to 25 cm. Tea leaves may be serrated, bullate, or smooth, stiff or flabby; the leaf pose ranges from erect to pendant, and the degree of pubescence varies widely from plant to plant. Moreover, the buds and young leaves contain a considerable number of trichomes, which decrease significantly as the leaves mature. In the harvest season, the shoot removed usually includes the bud and the two youngest leaves (Figure 1).

Tea can grow from subtropical climates to tropical climates, usually requiring considerable humidity and rainfall during the growing season [5]. Almost all of the commercially managed tea plantations are located in the highlands and on hill slopes, where the natural drainage is good. The ideal relative humidity for tea planting was maintained above 70% during the growing season. High humidity, fog, and dew are suitable for the growth of buds and young leaves. Maintaining an average annual temperature of 18–21 °C was of great significance to the growth and development of tea. The cultivated taxa of tea are composed of three main natural hybrids: C. sinensis (L.) O. Kuntze (also named China type), C. assamica (Masters) (also named Assam type), and C. assamica subsp. lasiocalyx (Planchon ex Watt.) (also named Cambod or Southern type) [6]. Tea plants have often been classified into green, albino, yellow, and ‘Zijuan’, based on the content of chlorophyll and anthocyanin present. Moreover, six types of tea (black tea (BT), green tea (GT), oolong tea (OT), white tea (WT), dark tea (DT), and yellow tea (YT)) with different flavor and aroma profiles were created through different processing techniques [7]. Different types of tea could meet the individual needs of customers and promote tea industry.

Many benefits of tea on human health have been reported, such as promoting caloric expenditure, reducing body fat, reducing the risk of dying from chronic diseases, improving insulin sensitivity, lowering the risk of contracting Alzheimer’s disease and other neurodegenerative diseases, preventing cancer, improving oral health, boosting fertility, and beneficially modifying gut bacteria [8,9]. The rapid development of molecular biology and sequencing technology provide an opportunity to study the chemical composition and corresponding molecular regulatory mechanisms in tea plants. However, so far, there has been no available updated review that aims to include all aspects of these valuable woody plants. This motivated us to summarize and compile the data published on the phytochemistry, nutritional, and pharmacological properties, omics research, and functional gene mining of tea plants in the form of a comprehensive review.

2. Uses and Potential Applications of Tea

General

Tea is not only processed as a non-alcoholic beverage [10], but is also used as a food addition to improve the texture and diversity of food [11]. In addition, the potential application of tea plants in the food processing, cosmetic, pharmaceutical, and nanomaterials industries were also reviewed in this paper.

2.1. Food Products

Tea was processed into various products or additives used in food processing. Tea-flavored foods not only meet the demand of consumers for green foods, but also have the combinatory effects of nutrition improvement and human health. Tea powder or crushed tea can be directly processed into tea bags, both instant or ready-to-drink (RTD) [12]. Moreover, several studies have reported that tea extracts or powder have been widely used in Chinese steamed bread [13], dried white salted noodles [14], biscuits [15], and bread [16]. Further analysis revealed that green tea powder improved the stability and viscoelasticity of wheat dough and the textural properties of fresh noodles [17]. In addition, tea catechins protected α-tocopherol from lipid oxidation in long-term frozen stored meat [18,19]. Tea-based food products, as one of the most important applications, have played important roles in increasing the food safety and diversity.

2.2. Cosmetic Products

In addition to food processing, tea extracts are widely used in the cosmetics industry, such as in face masks, face cleansers, facial toners, sun lotions, toothpastes, mouthwashes, shaving creams, aftershave lotion, deodorant, shampoos, and hair detanglers [20]. The anti-radical substances in tea extracts used as raw materials in cosmetology are beneficial to human skin, such as polyphenols, flavonoids, catechins, and vitamin C [21]. Hong et al., (2014) revealed that tannase-converted green tea extracts enhanced the activity and stability of skin-related enzymes [22]. The application of tea extracts in the cosmetics industry deserves more in-depth research.

2.3. Folk Medicines

In the aspect of health benefits, historical records have indicated that tea plants had been used as folk medicines. Bi et al. (2020) reported that the L-theanine in tea inhibited the proliferation and migration of vascular smooth muscle cells (VSMC) induced by the platelet-derived growth factor [23]. Nisar et al. (2021) first grafted L-glutamic acid to chitosan using γ-radiation to form hydrogel beads, which were used as an effective carrier for anticancer drugs. Isoleucine regulates blood sugar levels by promoting glucose absorption and degradation [24], and the absorption of glycine before bedtime effectively alleviates the symptoms of insomnia [25]. Moreover, tea polyphenols enhanced the antibacterial and antioxidant activity of ultrahigh molecular weight polyethylene (UHMWPE) in an artificial joint [26], and drinks with added catechins and (-)-Epigallocatechin gallate (EGCG) effectively decreased obesity, hypercholesterolemia, and hyperglycemia [27]. In addition, recent studies have revealed that tea polysaccharide was associated with various ailments, including reducing obesity, protecting hyperlipidemia, and inhibiting colitis-associated colorectal cancer, as well as processing greater hypoglycemic and hypolipidemic effects on type 2 diabetes [28]. Kitagawa et al. (2016) reported that tea flower saponins had anti-proliferative effects on human digestive tract carcinoma cells by inducing apoptosis and cell cycle arrest [29]. Vc in tea plant prevented lifestyle-related diseases, such as cancer, scurvy, and the weakening of vascular walls [30]. Therefore, the molecular mechanism of tea extracts in human diseases needed to be further explored in the future.

3. Bioactive Compounds

Tea contains a wide diversity of bioactive compounds, such as carotenoids, phenolic acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins, and terpenoids, which are responsible for the flavor and taste of tea, and also play beneficial and protective roles in human health [31,32]. A comprehensive review of biological activity and chemical constituents in tea is summarized in

Table 1. The content and composition of bioactive compounds in different types of tea.

Compounds	Contents (mg/g Dry Weight, DW)
	White Tea	Oolong Tea	Green Tea	Yellow Tea	Black Tea	Dark Tea
EGC	5.9–10.7 a	19.4–29.2 a	21.91–37.46 g	12.3–24.1 a	3.5–8.3 a	4.1–10.89 p,r
C	0.9–3.3 a	0.5–10.0 a	0.47–1.46 g	0.5–1.3 a	0.1–0.5 a	1.69–2.2 p,r
EC	2.7–4.7 a	5.9–7.9 a	3.78–6.7 g	3.5–8.1 a	1.9–4.8 a	5.7–6.63 p,r
EGCG	32.4–58.4 a	37.6–61.8 a	58.02–119.68 g	41.7–67.5 a	3.9–13.1 a	0.8–19.25 p,r
ECG	12.9–26.3 a	9.2–14.4 a	12.06–25.49 g	16.9–27.9 a	4.2–9.2 a	0.5–6.54 p,r
TC	101.4–153.9	72.6–114.3	96.24–190.79	74.9–128.9	13.6–35.9	12.79–45.51
CAFF	34.3–43.1 a	17.1–28.5 a	21.3–47.47 g,h	29.8–38.0 a	20.58–24.22 m	19.7–36.3 a
TPS	1.30 b	1.799–1.95 e	0.9904–1.3 i	3.6 l	1.645–2.092 n	7.225 q
Flavonols	2.3–18.9 c	3.885–5.021 f	5.85–11.93 j	-	15–26 o	11.173 q
Asp	0.451–2.234 d	0.571–1.29 d	1.04–2.15 g	0.212–0.41 d	0.39–1.25 m	0.102 r
Glu	0.59–1.407 d	0.403–1.017 d	1.36–2.04 g	0.16–0.396 d	0.45–1.73 m	0.042 r
Asn	0.874–5.335 d	0.046–0.451 d	-	-	0.11–0.91 m	-
Gln	0.259–0.595 d	0.053–0.598 d	-	0.107–0.555 d	0.18–3.11 m	-
Ser	0.359–0.903 d	0.135–0.293 d	0.34–1.07 g	0.194–0.31 d	0.17–1.11 m	0.122 r
Arg	0.208–0.713 d	0.015–0.217 d	0.58–1.87 g	0.113–0.245 d	0.12–0.80 m	0.019 r
Gly	0.029 d	0.001–0.054 d	0.03–0.04 g	0.255–0.283 d	0.03–0.09 m	0.074 r
Thr	0.155–0.42 d	0.072–0.16 d	0.13–0.33 g	0.117–0.189 d	0.16–0.41 m	0.012 r
Ala	0.204–0.938 d	0.153–0.655 d	0.16–0.25 g	0.303–0.373 d	0.07–0.79 m	0.065 r
Thea	3.571–8.002 d	0.726–5.248 d	3.07–21.18 g	8.26–10.72 d	0.89–17.27 m	2.318 r
Pro	0.215–0.83 d	0.015–0.103 d	0.41–0.62 g	0.212–0.286 d	0.12–0.78 m	0.018 r
GABA	-	-	-	0.135–0.189 d	0.07–0.55 m	0.03 r
Val	0.296–1.124 d	0.04–0.198 d	0.08–0.29 g	0.361–0.369 d	0.12–0.58 m	0.032 r
Ile	0.311–1.172 d	0.042–0.154 d	0.07–0.26 g	0.171–0.191 d	0.14–0.84 m	-
Leu	0.309–1.06 d	0.034–0.165 d	0.11–0.34 g	0.392–0.422 d	0.12–0.42 m	-
Phe	0.444–1.161 d	0.06–0.296 d	0.13–0.49 g	0.277–0.353 d	0.08–0.81 m	0.013 r
Trp	0.143–0.39 d	0.063–0.149 d	-	-	0.10–0.36 m	-
His	0.066–0.248 d	0.007–0.057 d	0.29–0.52 g	0.001 d	0.047–0.81 m	0.027 r
Lys	0.132–0.507 d	0.015–0.098 d	0.14–0.33 g	0.175–0.227 d	0.15–0.48 m	0.105 r
TFAA	8.484–27.07 d	2.451–11.203 d	7.94–31.52 g	11.443–15.51 d	7.93–29.48 m	2.961 r
VC	-	-	0.0174–0.043 k	-	0.094–0.122 k	-

Note: EGC, (−)-Epigallocatechin; C, (+)-Catechin; EC, (−)-Epicatechin; EGCG, (−)-Epigallocatechin gallate; ECG, (−)-Epicatechin gallate; TC, Total catechins CAFF, Caffeine; TPS, tea polysaccharides; Asp, Aspartic acid; Glu, l-Glutamic acid; Asn, l-asparagine; Gln, l-Glutamine; Ser, l-Serine; Arg, l-Arginine; Gly, Glycine; Thr, l-Threonine; Ala, l-Alanine; Thea, l-Theanine; Pro, l(–)-Proline; GABA, γ-aminobutyric acid; Val, l-Valine; Ile, l-Isoleucine; Leu, l-Leucine; Phe, l-Phenylalanine; Trp, Tryptophan; His, l-Histidine; Lys, l-Lysine; TFAA, Total free amino acids; Vc, Vitamin C. ^a: [33]; ^b: [34]; ^c: [35]; ^d: [36]; ^e: [37]; ^f: [38]; ^g: [39]; ^h: [40]; ⁱ: [41]; ^j: [42]; ^k: [43]; ^l: [44]; ^m: [45]; ⁿ: [46]; ^o: [47]; ^p: [48]; ^q: [49]; ^r: [50].

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3.1. Polyphenol Compounds

Polyphenols, including catechins, gallic acids, theaflavins, tannins, and flavonoids, are the major bioactive ingredients present in tea [51]. The content of polyphenols is mainly affected by the following factors: different organs, developmental stages, and tea processing techniques. The total polyphenol content in young leaves (58.6 mg/g dry weight, DW) is significantly higher than in old leaves (21.5 mg/g DW) and stem (8.5 mg/g DW) [52], and the total polyphenol content in GT (210.2 ± 15.4 to 143.2 ± 4.5 mg/g DW) was higher than that in BT (176.2 ± 4.2 to 84.2 ± 5.5 mg/g DW) [53]. Catechins and flavonol glycosides, the main contributor to the bitterness and astringency, displayed similar distribution patterns as polyphenols. The total catechin content in leaves (101.96 ± 3.34 mg/g fresh weight, FW) was significantly higher than those in the stems (46.22 ± 0.63 mg/g FW) and roots (2.86 ± 0.06 mg/g FW), and gradually decreased from the bud to the fourth leaf (125.73 ± 4.92 to 101.96 ± 3.34 mg/g FW) [48]. The content of catechins in the buds and one leaf from the different types of tea also differed: GT (96.24–190.79 mg/g DW) > WT (101.4–153.9 mg/g DW) > YT (74.9–128.9 mg/g DW) > OT (72.6–114.3 mg/g DW) > DT (12.79–45.51 mg/g DW) > BT (13.6–35.9 mg/g DW) [33,34,48,50]. Previous research revealed that the catechin content of tea leaves in summer (52.5 ± 3.6 mg/g DW) was higher than that in spring (37.7 ± 3.6 mg/g DW) [52]. However, the content of flavonol glycosides in the tea samples was 2.32–5.67 g/kg DW (calculated as aglycones), and no significant differences for the total flavonol glycosides among green tea, oolong tea, and black tea were detected [38]. However, kaempferol glycosides are more abundant in green teas, while oolong tea has more quercetin and myricetin glycosides. In black tea, quercetin glycosides are most abundant. Different types of tea and different tissues of the same type of tea contain different polyphenol compounds. Therefore, it is necessary to study the changes of polyphenol content in different types of tea and different tissues of the same type of tea.

3.2. Amino Acids and Peptides

Amino acids in tea plants, including theanine, glutamine, glutamate, proline, and aspartic, were mainly synthesized in the roots, which were further transported to new shoots, which contribute greatly to the pleasant taste and multiple health benefits of tea [54]. Previous studies reported that the total amino acid content in different organs of tea plant or the different types of tea was different. The total amino acid content was decreased from the top leaf (414.22 ± 1.0 mg/g DW) to the sixth leaf (6.56 ± 0.4 mg/g DW) [55]. A comparative analysis of the amino acid content in six types of tea was performed, and the result showed that GT had the highest content of amino acids (7.94–31.52 mg/g DW), followed by BT (7.93–29.48 mg/g DW), WT (8.484–27.067 mg/g DW), YT (11.443–15.519 mg/g DW), OT (2.451–11.203 mg/g DW), and DT (2.961 mg/g DW) [36,39,45,50]. Thus, the content and composition of amino acids were used to distinguish the raw materials or the different types of tea. Moreover, different types of amino acids in different organs of tea plants or the different types of tea have been reported [56]. The contents of Gln, Glu, and L-Theanine in the roots and stems were higher than those in the leaves and flowers [57]. GT has a high content of Asp, Glu, and L-Theanine, and WT processes high contents of Gly, Ser, Thr, and Pro. In addition, the total amino acid content was affected by various environmental factors, such as light quality and temperature [58]. Yellow light had the greatest effect on the amino acid contents, followed by purple light, orange light, and green light [59,60]. The contents of 13 individual amino acids, including Tyr, Ala, Arg, Cys, His, Ile, Leu, Lys, Phe, Ser, Thr, Val, and GABA, increased as the temperature rose from 15 °C to 25 °C [61]. Thus, the content and composition of amino acids was affected by the different organs, different varieties, field management, environment factors, and process conditions.

3.3. Alkaloids

Tea is one of the most important sources of alkaloids, generally found as purine alkaloids (e.g., caffeine, theobromine, and theophylline), which can be transformed into flavo-alkaloids [62]. Tea caffeine was the most widely consumed central nervous system stimulant [63]. The highest levels of caffeine (38.26 ± 1.19 mg/g DW) were found in the buds, followed by one bud with one leaf (37.57 ± 2.18 mg/g DW), one bud with two leaves (33.65 ± 0.55 mg/g DW), and one bud with three leaves (30.95 ± 0.91 mg/g DW) [64]. Another study revealed that WT contained the highest caffeine (36.2 mg/g DW), followed by YT (31.8 mg/g DW), BT (27.9 mg/g DW), OT (27.7 mg/g DW), GT (23.5 mg/g DW), roasted maté tea (11.3 mg/g DW), and maté tea (10.2 mg/g DW) [65]. In addition, some dimeric imidazole alkaloid metabolites of caffeine were found in black tea, which suggests that the opening of pyridine ring could occur during the manufacturing of black tea [66].

3.4. Aroma Compounds

Aroma compounds are important factors of sensory evaluation and quality, mainly including hexanoic acid, linalool, 2-phenylethanol. Doubtlessly, there are quite large variations among different kinds of tea, with respect of their volatile compound concentrations and profiles. A total of 168 volatile compounds have been identified in the tea infusions [67]. The concentration of aroma compounds in OT, WT, and BT ranged from 91 to 710 µg/g, which was higher than those in YT and DT (55–81 µg/g DW). However, GT had the lowest concentration of 20 µg/g DW aroma compounds. Moreover, Shao et al. (2021) have summarized the metabolite changes in fresh tea leaves under environmental and artificial stress conditions during preharvest and postharvest processing [68]. At pre-harvest, insect herbivory promotes aroma compounds. On the other hand, at postharvest, leaf wounding, drying, and low-temperature stress can effectively affect tea aroma. From the perspective of tea, this provides a novel view for utilizing stress for plant stress research, and proposes the controlled introduction of stress application for leaf-crop plants quality enhancement.

3.5. Saponins

Tea saponins mainly include sapogenins, glycosides, and organic acids. Around 90 saponins have been identified in different tissues of C. sinensis, including leaves (12 saponins), flowers (24 saponins), seeds (58 saponins), and wood tissues (19 saponins) [69]. The saponin contents accounted for 19% (dry weight %, DW %) in the freshly mature seeds and 7% (DW %) in flower buds, and decreased as the fruit ripeness and flower blooming progressed [69]. Wu et al. (2019) have quantified the total saponin content in the crude extract, and the purified saponin fraction of C. sinensis seeds were 19.57 ± 0.05% (DW %) and 41.68 ± 0.09% (DW %) using the UPLC–PDA method, respectively [70]. At present, there are few studies on saponins in various types of processed tea, and more research is needed.

3.6. Polysaccharides

Polysaccharides, the main bioactive components in tea, can reduce the risk of type 2 diabetes, obesity, and other metabolic diseases [28]. The polysaccharide content varied significantly among the different tissues of tea plants or the different type of tea. The polysaccharide content in tea flowers (2.7–22.78 mg/g DW) was lower than that in leaves (0.56–24.32 mg/g DW), and also lower than that in seeds (14.32–68.9 mg/g DW) [28,71]. The polysaccharide content was increased as the leaves matured [71]. The OT had the highest content of tea polysaccharides (TPS) (5.57–63.11 mg/g DW), followed by GT (6.53–54.4 mg/g DW), and BT (0–16.1 mg/g DW) [28]. It is of great significance to systematically study the content of polysaccharides in different tea varieties and their role in disease resistance.

4. Pharmacological Properties

Clinical and epidemiological studies have shown that drinking tea negatively correlates with the prevalence of chronic diseases [72]. Tea-drinking has been reported to exhibit anti-cardiovascular properties, antioxidant properties, anti-bacterial activity, anti-cancer and anti-diabetic properties, digestive health benefits, and immunomodulatory effects [73]. The corresponding functions of the main substances in tea are shown in

Table 2. The biological functions of main secondary metabolites in tea.

	Polyphenols	Free Amino Acids	Caffeine	Polysaccharides
Function	Antitumorigenesis A	Sleep peacefully, relieve tension G	Anti-fatigue L	Scavenging free radicals Q
	Antioxidant activity B	Decrease blood pressure H	Cardiotonic agent M	Antioxidant R
	Anti-cancer C,D	Promote relaxation, concentration and learning ability I	Vasodilation N	Immunostimulatory activity S
	Anticardiovascular disease E	Reduce hypertension J	Improve attention O	Anticancer T,U
	AntioxidantsxxxxxPrevent oxidative stress, modulate carcinogen metabolism F	Anti-obesity K	Improve physical endurance and cognitive function P	Antidiabetes V
	-	-	-	Antiobesity W

Note: ^A: [74]; ^B: [75]; ^C: [76]; ^D: [77]; ^E: [78]; ^F: [79]; ^G: [80]; ^H: [81]; ^I: [82]; ^J: [83]; ^K: [84]; ^L: [85]; ^M: [86]; ^N: [87]; ^O: [88]; ^P: [89]; ^Q: [90]; ^R: [91]; ^S: [92]; ^T: [93]; ^U: [94]; ^V: [95]; ^W: [46].

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4.1. Antioxidant Properties

Polyphenols have been shown to improve the health of mammals, owing to their high level of antioxidants [96]. Experiments conducted in vivo indicated that tea polyphenols elevated the contents of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and decreased the level of malondialdehyde (MDA) in rat serum [97]. Oral tea polyphenols improved ileal injury and intestinal flora disorder in mice infected with Salmonella typhimurium by resisting inflammation, enhancing antioxidant activity, and preserving tight junctions [98]. Moreover, EGCG reduced the generation of reactive oxygen species (ROS) and apoptosis, and partially decreased the phosphorylation of JNK1 and c-Jun following UVB irradiation [99]. ECG enhances the cellular antioxidant activity by increasing the level of expression of mitogen-activated protein kinase (MAPK) and antioxidant response element genes [100]. BT extracts displayed a dose-dependent protection against the 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced erythrocytes during oxidative hemolysis and copper-induced plasma oxidation [101]. The Pu-erh extracts activated the hepatic antioxidant system and reversed lipid peroxidation, regulating glucose levels by enhancing the glycogen synthesis and protein kinase (PK) activity, and preventing people from contracting liver disease [102] In a later study, isolation of more antioxidant compounds was conducted, and the roles in regulating the human diseases were further investigated.

4.2. Anti-Cardiovascular and Anti-Cancer Properties

Previous studies revealed that tea consumption is inversely associated with the development of cardiovascular disease by reducing cardiovascular risk factors, such as hyperlipidemia, hypertension, and hyperglycemia [103]. Decaffeinated GT extracts significantly decreased the ROS formation and NADPH oxidase activity in the vascular system, stimulated the phosphorylation of endothelial nitric oxide synthase (eNOS) and Akt in the immunoblotting of aortas, and improved endothelium-dependent relaxations in the thoracic aorta of Otsuka Long–Evans Tokushima Fatty (OLETF) rats [104]. The procyanidins (dimer and hexamer) and epigallocatechin in tea significantly inhibited the activity of angiotensin converting enzyme(ACE) to decrease the blood pressure [105]. The GT EGCG inhibited ileal apical sodium bile acid transporter activity, and increased the hepatic low-density lipoprotein receptor in rats [106].

Tea polyphenols reduce the risk of skin cancer [107]. EGCG inhibited oral cancer by producing mitochondrial ROS and dysfunction [108]. Ingesting a dosage of EGCC significantly improved the efficacy of radiotherapy in patients [109]. Moreover, the therapeutic effect of the combination of tea polyphenols and other drugs was investigated [110]. Tea polyphenol with taurine can reduce the level of lipopolysaccharides in rats and protect the liver [111]. Tea polyphenols and Trolox inhibit gene mutations, base detachment, and breaks in DNA strands caused by an excessive number of oxygen free radicals [96]. In addition, tea also exhibited anticancer activity in vivo. Calgarotto et al. (2018) found that GT possessed anticancer effects in HL-60 human leukemia xenograft mice, reduced tumor growth via mediation of the G1 phase cell cycle arrest, promoted apoptosis via the regulation of caspase-3, Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma extra large), Bax (Bcl-2-associated X protein), MCL-1, LC3-I, and LC3-II, and initiated autophagic progression via the activation of autophagy proteins [112]. The GT catechins inhibited the proliferation of human colon cancer cells (HCT-116 and SW-480) [113]. Tea played an important role in anti-cardiovascular and anti-cancer activities, which laid solid foundations for the applications of tea extracts in medicine.

4.3. Anti-Obesity and Antidiabetic Properties

Tea polyphenols influence the neuroendocrine regulation of appetite, reduce the emulsion and absorption of lipids and proteins, promote digestion, inhibit the differentiation and proliferation of preadipocytes, reduce lipid production, and promote lipolysis and lipid metabolism [114]. Previous studies revealed that tea consumption reduced the risk of diabetes mellitus (DM) [115,116], decreased the amount of fasting blood sugar, and controlled obesity [117]. Mareau et al. (2009) revealed that EGCG promoted the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), inhibited the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes, prevented cytokine-induced β-cell damage, and regulated the pattern of expression of genes involved in the insulin signal transduction pathways and glucose uptake [118]. Theaflavins reduced the risk of impaired glucose tolerance [119], blocked α-glucosidase activity, and decreased glucose production in the intestine [120]. Due to the effects of tea on obesity, the investigation of molecular mechanism of tea extracts in anti-obesity was imperative.

4.4. Neuroprotective Effects of Tea

Epidemiologic study revealed that tea consumption greatly decreased the risk of Parkinson’s disease and Alzheimer’s disease (AD) [80,121]. The neuroprotective effects of theanine were mainly due to its ability to block the binding of L-glutamic acid to glutamate receptors in the brain and regulate the extracellular concentration of glutamine [80]. Caffeine and theaflavins inhibited the adenosine A2A receptor and increased the antioxidant properties [122]. The neuroprotective action of EGCG was involved in regulating the calcium homeostasis, maintaining the activities of extracellular mitogen-activated protein kinases (MAPK), protein kinase C (PKC), and antioxidant enzymes [121]. Weinreb et al. (2007) shed some light on the antioxidative-iron chelating activities of EGCG underlying its neuroprotective/neurorescue mechanism of action [123].

4.5. Antimicrobial Properties

The tea catechins, including EGCG, ECG, EGC, and EC, possess antimicrobial effects which damage the bacterial cell membrane, inhibit fatty acid synthesis, and block enzyme activity [124]. ECG, EGC, and EGCG possess broad-spectrum antibacterial effects [62]. Shi et al. (2018) found that tea tree oil exhibited good antibacterial activities against two food-borne pathogenic bacteria by damaging the bacterial cell membrane [125]. Nakayama et al. (2012) reported that GT extracts interacting with bacterial cell wall-associated proteins form high-molecular weight complexes inhibited the uptake and secretion of substrates, and inhibited enzyme activity [126].

5. Omics Research

5.1. Genomics Research

With the advent of sequencing technology, functional genomics has become fundamental in the biological research of tea plants. A comprehensive genomic and transcriptomic database of tea plants (TPIA, tea plant information archive) has been constructed, which is an indispensable resource for studying tea plants [127]. The draft genome sequence of “Yunkang 10” and “Shuchazao” cultivars, which produced a ~3.02 Gb and 2.94 Gb genome assembly, respectively, were constructed [128,129], and further analysis revealed that the Chinese cultivated tea plants originated from the southwest, and later spread to west Asia through introduction. Zhang et al. (2020) constructed a high-quality chromosome-scale reference genome for an ancient tea tree (DASZ), clarified the pedigree of tea cultivars, and revealed the key contributors in the breeding of Chinese tea in combination with the RNA-Seq data of 217 diverse tea accessions [130]. In addition, whole-genome resequencing of 139 tea accessions around the world revealed that, during domestication, the selection for disease resistance and flavor in the C. sinensis (CSS) populations was stronger than those in the C. sinensis (CSA) populations. Niu et al. (2019) performed the genotyping-by-sequencing (GBS) of 415 tea accessions from Guizhou Plateau, and further analysis revealed that 415 tea accessions were classified into four groups: pure wild type, admixed wild type, ancient landraces, and modern landraces [131]. Thus, the whole-genome sequencing and resequencing become effective tools to investigate the origin of tea plants, mine functional genes, and identify the difference among the different tea varieties.

5.2. Transcriptomics Research (RNA-Seq)

The RNA-Seq data can be involved in many aspects, including sequence information, gene expression profiles, and gene function prediction [132]. Transcriptome analysis revealed that epigenetic mechanism, phytohormone signaling, and callose-related cellular communication may be involved in bud dormancy [133], and the gravitropism response and polar auxin transport were associated with the formation of zigzag-shaped shoots in tea plants [134]. Moreover, transcriptome analysis of self- and cross-pollinated pistils of “Fudingdabai” and “Yulv” cultivars revealed that three genes (UGT74B1, MCU2, and RLK) were involved in regulating the SI process of tea plants [135]. A transcriptome analysis of “Zijuan” tea plant reported the genes associated with several primary metabolic pathways, including flavonoid, theanine, and caffeine biosynthesis [136]. The molecular mechanism of theacrine metabolism of bitter tea (Kucha, C. sinensis) was revealed by transcriptome analysis [137]. RNA-Seq technology was not only used to explore the regulatory mechanism of growth and development, but also to reveal the response mechanism of tea plants to environmental stresses, including cold acclimation [138], drought stress [139], shade [140], thermal stress [141], and simulated acid rain [142]. In addition, transcriptome analysis was also used to reveal the molecular mechanism of the different nitrogen form-induced oxidative stress [143], nitrogen uptake [144], selenium accumulation [145], fluorine absorption and transportation [146], and the molecular mechanism of aluminum tolerance and accumulation in tea plants [147]. Aside from this, transcriptome analysis was also used to analyze the defense mechanism of plants against various biotic stresses, including the identification of candidate genes involved in blister blight defense [148], genes associated with resistance to Colletotrichum camelliae [149], and the defense mechanism of tea plants induced by Helopeltis theivora [150]. Although transcriptomics was widely used to study the plant growth and development and stress response, the identification of molecular mechanisms of tea extracts in human health using transcriptome analysis was very rare.

5.3. Metabolomics

Tea is rich in secondary metabolites, including flavonoids, theanine, and caffeine, which are the primary sources of the rich flavors, fresh taste, and health benefits of tea [151]. Metabolomic analysis was widely used to detect the number, composition, and content of the metabolites, and identify the differential metabolites in various organs, the different type of tea and different processing technologies [152,153,154]. A total of 527 non-volatile and 184 volatile metabolites have been identified by non-targeted metabolomics method in tea leaves during green tea processing [155], and 782 metabolites have been identified in tea leaves during oolong tea processing, 46 of which were used as biomarkers [156]. The identification of 68 differential metabolites in 6 different organs of Oolong tea cultivar was performed based on non-targeted metabolomic analysis, and further analysis revealed that 3 compounds (tricoumaroyl, spermidine, and dicoumaroyl putrescine) were specifically distributed in tea flowers [157]. Comparative metabolic analysis of WT, GT, and BT processed by the same fresh tea leaves showed that there were significant differences in the content of amino acids, catechins, dimeric catechins, flavonol, and flavone glycosides, as well as aroma precursors [56]. Moreover, 98 compounds were identified in 6 Chinese dark teas (CDTs), and further analysis revealed that dark teas from Yunnan and Guangxi provinces could be classified into one group, and other CDTs belonged to the other cluster [158]. Furthermore, the content and composition of the different metabolites was associated with processing time, temperature, and the microorganism in question. Tea samples with various fermentation durations identified 61 differential phenolic compounds, including catechins, dimeric catechins, flavonol glycosides, amino acids, phenolic acids, alkaloids, and nucleosides [159]. Non-targeted metabolomics analysis revealed that the first stage of PF (pile-fermentation) was crucial in transforming the original secondary metabolites, whereas long-term PF decreased the contents of flavan-3-ols and gallic acid [160]. LC–MS-based metabolomics revealed that the thermally induced degradation and epimerization of catechins, as well as the formation of N-ethyl-2-pyrrolidinone, substituted flavan-3-ols during large-leaf yellow tea roasting [161]. Metabolomics analysis of tea leaves fermented by Aspergillus niger, Aspergillus tamarii, and Aspergillus fumigatus showed that the composition of flavonoids, glycerophospholipids, organo-oxygen compounds, and fatty acids resulting from Aspergillus fermentation had changed [162]. Apart from above these, metabolomics analysis was also used to explore the effect of environmental factors on metabolites in tea leaves, such as nitrogen [163], excessive calcium [164], fluorine [165], anaerobic treatment [166], cold stress [167], drought stress [168], UV radiation [169], blue light [170], shading [171], and storage and harvest time [172,173]. The effect of tea plants–soybean/Chinese chestnut intercropping on the secondary metabolites of tea plants was performed based on metabolomics analysis [174].

6. Function Genes

6.1. House-Keeping Genes

House-keeping genes play important roles in maintaining basal cell functions, which are constitutively expressed in different organs or at different stages [175]. The selection of appropriate reference genes is critical for gene expression analyses. Previous studies reported that three genes (CsACT, CsPPA2, and CsTBP) were selected as reference genes during the turnover and withering treatments of tea leaves [176]. A study of reference genes in tea plants treated with different biotic stresses reported that CLATHRIN1 and GAPDH1 were the best reference genes for jasmonic acid treatment, ACTIN1 and UBC1 for leaves infested with the camellia aphid (Toxoptera aurantia), UBC1 and GAPDH1 for leaves infested with the tea green leafhopper (Empoasca onukii), and SAND1 and TBP1 for leaves treated with regurgitant from the tea geometrid (Ectropis obliqua) [177].

6.2. Stress-Related Genes

Plants, as sessile organisms, have evolved a complex mechanism to adapt to various environmental stresses, such as drought, mechanical damage, and high and low temperatures [178,179]. Overexpression of CsCOR1 (encoding cold-regulated proteins) and CsHSP17.2 (encoding heat shock protein) genes in transgenic tobacco and Arabidopsis enhanced drought tolerance, salt tolerance, and thermotolerance, respectively [180,181]. The expression level of HXKs (hexokinase-encoding genes), FRKs (fructokinase-encoding genes), CsGolS1 (gactinol-synthase-encoding genes), and two CsF3Hs (flavonoid 3-hydroxylase-encoding genes) was increased after abiotic stresses [182,183,184]. Recent studies have reported that UGT91Q2 (glucosyltransferase-encoding gene), CsWRKY26, and CsbZIP18 from C. sinensis were involved in the modulation of cold stress tolerance, drought tolerance, and negatively regulate freezing tolerance, respectively [185,186,187]. In total, three CsCAD genes (CsCAD1-3), encoding cinnamyl alcohol dehydrogenases, were upregulated after mechanical damage and insect attack [188].

Insect and disease are damaging stressors that threaten the cultivation of tea plants. The expression level of CsHPL (hydroperoxide lyase-encoding gene) and CsGolS genes were significantly increased after insect attack and tea inchworms eating the crop [183,189]. The genes encoding lipoxygenase (LOX) and phenylalanine ammonia lyase (PAL) were isolated from tea plants as pathogen-induced genes [190]. Overexpression of CsTLPs from C. sinensis encoding thaumatin-like proteins in transgenic potato (Solanum tuberosum) displayed greater fungal resistance by upregulating the transcripts of StPAL and StLOX genes [191,192]. Liu et al. (2021) reported that transcription factor WRKY14 mediates the resistance of tea plants to blister blight [193]. Environmental factors significantly affect plant growth and the biosynthesis of secondary metabolites. Mining more stress-specific genes is an effective way to enhance resistance using modern biotechnologies.

6.3. Metabolism-Related Genes

A considerable number of genes involved in metabolite biosynthesis were isolated and identified from tea plants. The CsF3H gene was cloned from tea plants, and transgenic Arabidopsis plants overexpressing CsF3H genes significantly increased the flavonoid content in the seeds [184]. Su et al. (2018) reported the UGT73A17 gene was involved in the biosynthesis of flavonoid glucosides [194], and CsGSTF1 encoding phi (F) class glutathione transferase positively regulated the anthocyanins biosynthesis [195]. Previous studies revealed that MYB family genes were associated with flavonoid biosynthesis [196]. CsMYB4a negatively regulates the biosynthesis of phenylpropanoid and anthocyanins [196], while CsMYB6A and CsMYB75 positively regulate anthocyanins biosynthesis, respectively [195,197]. Wang et al. (2018) also reported that the overexpression of CsMYB5b in transgenic tobacco significantly increased the content of catechin monomers and polymers in transgenic tobacco lines, compared with WT [198]. Moreover, MYB interacting with bHLH and WD40 form ternary WBM complexes in tea plants, and these regulated flavan-3-ols biosynthesis [199]. A total of three CsLARa-c genes encoding leucoanthocyanidin reductase and transcription factor CsHB1 significantly increased the catechin content [200,201]. In addition, an Arabidopsis mutant (tds4-2) that overexpresses the CsANS gene significantly increased the epicatechin content in seeds [186]. Wang et al. (2021) reported that CsDOF regulates glutamine metabolism in tea plants [202]. Although many metabolic genes were identified in tea plants, the functions of most genes were still unclear. Thus, the functions of most genes should be investigated in model plants using the genetically modified method.

Tea aroma is one of the most critical aspects of tea quality. Beta-primeverosidase from tea plants specifically hydrolyze aroma precursors of beta-primeverosides to produce numerous aromatic compounds [203]. The CsSAMT gene, encoding salicylic acid carboxyl methyltransferase, catalyzes SA to generate MeSA with floral aromas [204]. Theanine also plays an important role in tea flavor and quality [205,206]. A comparative genomics analysis suggests that the glutamine synthase (GS) family of genes differentiates into theanine synthase (TS) genes [207]. Sasaoka and Kito (1964) purified and identified TS for the first time [208]. Overall, two genes (TS1, DD410896 and TS2, DD410895) were amplified from the tea plant cDNA library. Further analysis showed that the sequence similarity between TS1 and GS3 is as high as 99%, and the sequence similarity between TS2 and GS1 is as high as 97%. Liu et al. (2017) revealed that the glutamine:2-oxoglutarate aminotransferase (CsGOGAT) gene played important roles in regulating the theanine content in the postharvest leaves of tea plants treated under different temperatures and shade conditions [140]. So far, there are few studies on aroma-related genes. In the future, mining aroma-related genes should be intensified using the omic analysis.

7. Conclusions and Future Perspectives

Tea is the widely consumed non-alcoholic beverage in the world with essential economic and health benefits, since its leaves contain polyphenols, catechins, caffeine, theanine, saponin, and volatile oils. In this review, we summarized the content and distribution of main secondary metabolites in different types of tea and different organs of tea plants, such as polyphenol compounds, amino acids, alkaloids, aroma compounds, saponins, and polysaccharides. Moreover, the application of these secondary metabolites in food processing, cosmetics industry, and pharmaceutical properties were comprehensively investigated and summarized. Omics analysis, including genomics analysis, transcriptomics analysis, and metabolomics analysis, were reviewed in this study. The aim of this review was to systematically compare the differences of secondary metabolites in six different types of tea, and the molecular mechanisms regulating the biosynthesis and metabolism of main secondary metabolites was explored to identify the key structure genes and transcription factors.

Omics analyses, including genome, transcriptome, proteome, and metabolome, provide effective tools to mine functional genes and important regulatory factors, since they constitute a substantial amount of gene information involved in regulating the molecular mechanisms of different biological process in the new plant variety. A combined multi-omics analysis established relationships between differential metabolites and differentially expressed genes, which was used to reveal the molecular mechanisms of metabolite accumulation. Identification of a large number of functional genes can help us to understand the growth and development of tea plants, control importance traits, reveal the molecular mechanisms of secondary metabolites, and improve stress resistance, which provides a molecular basis for breeding. In addition, the sample extraction techniques severely restrict the identification and isolation of individual secondary metabolites in tea plant. Moreover, the pharmacological mechanisms of some bioactive ingredient in tea are still unclear due to the lack of animal studies and clinical trials. With the innovation of new technology and the development of molecular biology, the research on bioactive ingredients mainly focuses on the isolation and extraction, structural analysis, metabolic pathway analysis, and molecular mechanism.