Phytochemistry

: Any product generated from food sources that offer additional health advantages over and above the essential nutritional content present in foods is referred to as a nutraceutical under the broad umbrella term. The catechins in Camellia sinensis (Theaceae) namely (-)-epicatechin, (-)-epicatechin-3-gallate, (-)- epigallocatechin, and (-)-epigallocatechin-3-gallate (EGCG), which can be used as nutraceuticals in food or as a component of food items has been discussed. Catechins being polyphenols and antioxidants are found to have a wide range of therapeutic application like weight loss, anticancer, anti-inflammatory, and a few more therapeutic applications, through various mechanisms like stimulating AMP-activated protein kinase, enhanced apoptosis, decreased expression of interleukin (IL)-6 and IL-8. The most recent method for extracting catechins include combining the extraction processing of PEF or IPL with Subcritical water extraction. Food additives have been mixed with green tea extracts to develop a desired formulation like chewing gum and capsule. As green tea catechins are a beneficial phytoconstituents to improve overall health, its prospects include formulation of a gelatin gummy formulation which will improve its palatability by masking the bitter taste. Gelatin gummy formulation can be carried conveniently and will provide easy access to the consumer as compared to green tea. Furthermore, we found a scope to develop an analytical method for EGCG and carry out its validation by HPLC which will be more reliable and cost-efficient in comparison to the existing UHPLC methods for EGCG.


Introduction
Nutraceuticals are defined as "specially tailored formulations" created to meet certain dietary needs and/or provide preventive healthcare. Dr. Stephen De Felice coined the phrase "nutraceutical" in 1989, combining the words "nutrition" and "pharmaceutical." These are foods or components of foods that have a variety of health advantages, such as the ability to treat and/ or prevent disease (1).
The classification of Nutraceuticals is given in Figure 1. The transition to nutraceuticals is being driven by a number of factors such as:  More and more people are worried about the cost of healthcare (2).

Figure 1 Classification of nutraceuticals
The last ten years have seen a surge in interest in the antioxidant properties of dietary plant polyphenols as we can see the classification of antioxidants in Figure 2. Long-term intake of diets high in plant polyphenols may protect against the onset of malignancies, cardiovascular disease, diabetes, osteoporosis, and neurological illnesses, according to epidemiological research and related meta-analyses (5).
The dietary sources of polyphenols have drawn a lot of interest. Particularly, the polyphenolic elements in various tea brews have been thoroughly investigated. After water, tea is the beverage that is consumed most frequently. Due to the strong correlation between drinking tea and having positive health effects, tea polyphenols have drawn a lot of public interest. Epigallocatechin-gallate (EGCG), epigallocatechin (EGC), epicatechin-gallate (ECG), and epicatechin (EC) are among the catechins found in green tea extract. The most abundant polyphenol in green tea is EGCG (6). One of the most numerous and extensively dispersed classes of natural compounds in the plant kingdom is dietary phenolics, often known as polyphenols. Almost 4000 flavonoids have been discovered among more than 8000 phenolic structures currently known. While being classified chemically as substances having phenolic structural characteristics, polyphenols are a wide class of natural products that include many subgroups of phenolic substances. Rich sources of polyphenols include fruits, vegetables, whole grains, and various types of meals and beverages like tea, chocolate, and wine (7).

Biological Source
Epigallocatechin gallate is the major polyphenolic component of dried C. sinensis belonging to the family Theaceae. EGCG is the biologically active catechin accounting for at least 50% of the total catechin content in C. sinensis leaves (9).

Geographical Indications
The tea tree, C. sinensis, is thought to have started in an evergreen forest. According to the report, largescale tea tree cultivation is concentrated mostly in the plateau sections of Japan's Kyushu and Honshu Islands.
China accounts for over 73% of the global output of green tea. The production of green tea in Vietnam and Indonesia, which together account for about 5% of global production, is especially noteworthy. India is one of the world's top producers of green tea (10).

Extraction of green tea
The development of an appropriate method for the extraction, separation, and stability of catechin concerns scientists and industry very much. Several key factors have a considerable impact on catechin extraction, including pH, temperature, frequency, and timing of extractions, and the type of solvent employed.
This is a discussion of some popular methods for extracting catechin from green tea leaves (12).
The efficiency of pulsed electric field (PEF) and Intense Pulsed Light (IPL) as a pre-treatment method for improving the extraction of tea catechins from green tea leaves was confirmed by Hee-Jeong Hwang et al.
SWE is a technique for retaining water in a liquid condition for extraction at a temperature between 100 °C (the boiling point of water) and 374 °C (the critical point of water) while elevating the boiling point of water in a high-pressure environment (about 10 MPa) (14). Similar to organic solvents, the polarity of water shifts from polar to nonpolar as the temperature rises, making it easier to dissolve non-polar and moderately polar compounds (13).
The PEF technique involves submerging a sample with two electrodes in water or solvents and delivering high-voltage electric pulses for a brief period time. PEF has historically been employed primarily as a nonthermal sterilization technique, however, it is currently used as an extraction technique in and of itself or to increase extraction effectiveness (15).
One of the newer non-thermal disinfection techniques that use intense, brief bursts of light is called IPL. However, current research from multiple studies has shown that after IPL treatment of the plant surface, the extraction efficiency of health-promoting chemicals from plants is boosted (16).
Even while numerous catechins are found in trace amounts, EGCG is by far the most prevalent green tea polyphenol by weight. It consists of a pyrogallol ring (ring A), a benzenediol ring (ring B), a galloyl group, and a tetrahydropyran moiety (ring C) (with the B ring) (18,19) as shown in Figure 4. The other catechins present are ECG, which lacks a hydroxyl group on the pyrogallol B ring, and EGC (20).

Pharmacokinetics of Green Tea Catechins
EGCG is quickly absorbed by the intestinal system, disseminated, metabolized in the liver and colon, and can be reabsorbed from the gut by enterohepatic re-circulation, according to studies on ADME in rats and dogs. The resultant metabolites are eliminated by the urine and biliary systems. However, after oral delivery, only minute amounts of EGCG are found in the urine (8). Green tea catechins mostly enter the body through the jejunum and ileum, where they are diffused through epithelial cells in a para-cellular manner (27).
After absorption, EGCG is present in plasma in a significant amount (>75%) in a free form (28).

Pharmacology of Green Tea Catechins
Green tea catechins (GTC) work by lowering oxidative stress, preventing inflammatory events, reducing platelet aggregation, and stopping the growth of vascular smooth muscle cells to prevent atherosclerosis, hypertension, endothelial dysfunction, ischemic heart diseases, cardiomyopathy, cardiac hypertrophy, and congestive heart failure by raising NO levels (29), GTC also had anti-atherosclerotic effects on smokers' defective vasculature (30). Several in vitro and in vivo experimental investigations have demonstrated the effectiveness of tea's bioactive components in preventing cardiovascular diseases. More than one cup of green tea every day lowers the risk of coronary heart disease by 10% (31). EGC decreased the synthesis of IL-8 in human ECs, which can lessen the atherosclerosis brought on by inflammation (32).
According to the study conducted by Antonello M., et. al. (2007). Male Sprague Dawley rats aged 13 were given a vehicle, a high (700 g/kg/d) or a low (350 g/kg/d) Angiotensin II dose for 13 days and were randomly allocated to drink water with or without green tea extract which likely inhibited superoxide anion production or scavenged it to prevent hypertension and target organ damage brought on by a high Angiotensin II dosage (33).
In mice, GTC and EGCG delayed the tail bleeding time, reduced death from pulmonary thrombosis, and inhibited human platelet aggregation in vitro and ex vivo (34).
A total of 12 weeks of treatment with high doses of green tea extract helped women with central obesity lose considerable amounts of weight, shrink their waistlines, and consistently lower their levels of LDL and total cholesterol in their blood (35).
According to the study conducted by Li The dextran sulfate sodium (DSS)-treated mice model of ulcerative colitis was used to study the effects of EGCG. For three days, only EGCG (3.2 mg/g) was consumed. Treatment with EGCG reduced spleen and colon lengthening brought on by DSS. When compared to DSS-treated controls, EGCG also reduced the levels of the proteins IL-1, IL-6, and tumor necrosis factor, as well as colonic lipid peroxides (38).

Pharmaceutical Formulations of Green Tea Catechins
Food additives such as vitamin C, xylitol, sucrose, citric acid, butylated hydroxytoluene, dibutyl hydroxytoluene, and ethylenediamine tetraacetic acid have been mixed with green tea extracts and extracted EGCG. Also, they were diluted in milk, soy, and rice beverages, as well as citrus juices like orange, grapefruit, lemon, and lime (39).

Pharmaceutical Analysis of Green Tea Catechins
Several detection methods have been developed for tea catechin analysis, which is largely based on liquid chromatography (LC) methods like High-Pressure Liquid Chromatography, High-Performance Thin Layer Chromatography, and Ultra High-Pressure Liquid Chromatography for getting a good separation, identification, and quantification of the catechins.

HPLC estimation of green tea catechins
HPLC methods according to previous work has been listed in Table 3.

UHPLC estimation of green tea catechins
UHPLC methods according to previous work have been listed in Table 4.

Conclusion
The most commonly consumed beverage is tea. Due to the strong correlation between drinking tea and having positive health effects, tea polyphenols have drawn a lot of public interest. In this review article pharmacognosy, pharmacological action, phytochemistry, analytical work, and pharmaceutical formulations of green tea catechins have been listed by carrying out a literature review on reported studies. As green tea catechins are believed to improve overall health, we recommend the formulation of a gelatin gummy which will improve its palatability by masking the bitter taste, carry conveniently, and have easy access as compared to green tea. Furthermore, we found the scope to develop an analytical method for EGCG and carry out its validation by HPLC which will be more reliable and cost-efficient as only UHPLC methods exist for EGCG.