Green Tea Catechins: Biologic Properties, Proposed Mechanisms of Action, and Clinical Implications

Botanicals have dominated pharmacopoeias across the globe for thousands of years and continue to serve as a valuable source of therapeutic compounds because of their vast biosynthetic capacity.¹ They are not only an important source of new pharmaceuticals, but also have a long history of safe human use. Botanicals were among the first pharmaceuticals to be used in the United States.² In the 1800s, for example, herbalists, midwives, and physicians of all types were explicitly trained in the use of plants as medicinal agents. However, the use of botanicals has steadily declined since the early 1900s (Figure 1). This decline was largely triggered by the Flexner Report of 1910, commissioned by the American Medical Association and the Carnegie Foundation, which suggested that only trained physicians should be permitted to prescribe medications. Moreover, Flexner allegedly doubted the validity of all forms of therapy other than those based on extensive scientific research, including direct examination of a treatment's effect on human physiology and biochemistry; he deemed training in any other approach to medicine as tantamount to quackery. Thus, many training institutions that stressed the use of what would now be called complementary or alternative medical disciplines were closed down. Concurrent with the loss of training institutions as champions of such agents as botanical derivatives, an increasingly more challenging regulatory environment followed the establishment of the precursor to the US Food and Drug Administration (FDA) in 1906, as well as numerous legal restrictions on the use of nonpatent medications (eg, the Food, Drug, and Cosmetic Act of 1938). In this milieu, the myriad of unknown information related to botanical products conceivably translated to the low prescription botanical drug availability in the United States compared with other nations.^3-5 Despite published guidelines by the FDA and support from several agencies, including the World Health Organization, the Office of Dietary Supplements, and the National Center for Complementary and Alternative Medicine, development of botanical drugs continues to be a challenging process.^6-9 In fact, only about 25% of prescription drugs used today are derived directly from plants.¹

Green tea is recognized worldwide for its wide array of health benefits, most of which are attributed to the polyphenols or flavonoids.¹⁰ Catechins are the major flavonoids in green tea leaves, comprising approximately 30% to 40% of the dry leaf weight.^10-12 During the fermentation process, green tea leaves are quickly heated after harvesting to inactivate the main oxidizing enzyme, polyphenol oxidase. This procedure prevents oxidation and preserves most of the constituent catechins.^13,14 Epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC) are the four major catechins found in green tea (Table 1).¹⁴Among these, EGCG is present in the highest concentration and considered the principal therapeutic agent of green tea leaves. Even though the beneficial effects of catechins are most frequently attributed to EGCG, the various catechins may work in synergy to efficiently modulate complex biologic pathways. In cultured human cervical carcinoma cell lines (HeLa cells), the amount of EGCG required to prevent cell growth and inhibit a cancer-associated, cell surface-located nicotinamide adenine dinucleotide phosphate oxidase was reduced 10 times by combination with EC, EGC, or ECG, thus supporting the synergistic activity between several catechins.¹⁵

Catechins are well-known for their antioxidant properties and primarily characterized by their ability to scavenge reactive oxygen species.^10,13 They may also function indirectly as antioxidants through their effects on several transcription factors and