BACKGROUND
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 Catechins
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
