In the book “Yojokun” published in the Edo period, Ekiken Kaibara described that according to the ancient Chinese medical doctor, long-term drinking of green tea would result in a lean body by removing body fat. Evidence has accumulated to show that the ingestion of green tea and tea catechins leads to a reduction in body fat as described in recent reviews.86–88) The stimulation of hepatic lipid metabolism might be a factor responsible for the anti-obesity effects of tea catechins. Tea catechins are suggested to inhibit cell growth by suppressing lipogenesis in human MCF-7 breast cancer cells through down-regulation of fatty acid synthase gene expression in the nucleus and stimulation of cell energy expenditure in the mitochondria.89) The experimental data indicated that the suppression of fatty acid synthase gene expression by tea polyphenols may lead to down-regulation of EGFR/PI3K/Akt/Sp-1 signal transduction.
In addition to EGCG’s effects described above, we observed that oral administration of an EGCG-free green tea fraction reduced the hepatic gene expression of PEPCK and G6Pase.83) This fraction also reduced the hepatic gene expression of lipogenic enzymes such as fatty acid synthase, 4-hydroxymethylglutaryl CoA reductase, acetyl CoA carboxylase α, and ATP-citrate lyase in association with the reduced gene expression of sterol response element-binding factor (SREBF)-1 and SREBF-2, key transcription factors for the gene expression of lipogenic enzymes90) (Fig. (Fig.6).6). In accordance with the results for these changes in hepatic gene expression of lipogenic enzymes, the plasma levels of triglycerides and cholesterol of mice given a diet containing the EGCG-free fraction were significantly reduced90) (Table (Table1).1). The plasma glucose levels were not altered significantly, but tended to be reduced (Table (Table1).1). Thus, green tea contains some component(s) other than catechins which may have anti-obesity and anti-atherosclerotic effects.
Anti-atherosclerotic effects of catechins have often been reported. For example, Muramatsu et al.91) found that tea catechins decreased plasma total cholesterol, cholesterol ester, and total cholesterol-HDL-cholesterol (VIDL-+LDL-cholesterol) levels and lowered the atherogenic index (VLDL-+LDL-cholesterol/HDL-cholesterol), indicating that they exert a hypocholesterolemic effect, in cholesterol-fed rats. Catechins have been shown to prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression.92) The ability of green tea to prevent cell invasion and matrix degradation might contribute to its protective effect on atherosclerosis and cancer.
A recent report has revealed a potential role for green tea in the prevention of cardiovascular disease.93) A population-based, prospective cohort study initiated in 1994 among 40,530 Japanese adults aged 40 to 79 years without a history of stroke, coronary heart disease, or cancer at baseline indicated that over 11 years of follow-up, 4209 participants died, and over 7 years of follow-up, 892 participants died of cardiovascular disease and 1134 participants died of cancer. The results of statistical analyses indicated that green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease.
It was shown that EGCG suppressed experimental autoimmune encephalomyelitis induced by proteolipid protein 139–151 in mice.94) EGCG reduced clinical severity when given at initiation or after the onset of encephalomyelitis by both limiting brain inflammation and reducing neuronal damage. Mice given EGCG orally showed abrogated proliferation and TNF-α production in encephalitogenic T cells. Proposed models for signal transduction pathways modified by EGCG include: EGCG is capable of inhibiting both catalytic activities of the proteasome, including the activation of NF-κB, and the amount of ROS produced (Fig. (Fig.4).4). In lymphocytes, this leads to decreased proliferation and production of TNF-α, while in neurons, it results in less damage. Additionally, the antioxidative effects of EGCG on neurons might involve the NF-κB pathway as well, since an oxidative stress can induce production of NF-κB, which regulates the expression of a variety of factors contributing to cell proliferation, inflammation, and neuronal damage. Thus, a natural green tea constituent may open up a new therapeutic avenue for young disabled adults with inflammatory brain disease by combining, on the one hand, anti-inflammatory and, on the other, neuroprotective capacities.
Rezai-Zadeh et al.95) showed that EGCG modulated cleavage of the amyloid precursor protein and reduced cerebral amyloidosis in Alzheimer transgenic mice. Daily consumption of green tea catechins may delay memory regression in aged mice as shown by Unno et al.96) Thus, green tea catechins are expected to have beneficial effects on brain functions. A recent epidemiological study has indicated that consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.97)
Methylated EGCG ((−)-epigallocatechin 3-O-(3-O-methyl) gallate) was demonstrated to inhibit degranulation from cells that had been stimulated with the calcium ionophore A23187 in the human basophilic cell line KU812.8,98) This result indicates that methylation of EGCG may be an effective means of modifying catechins to inhibit degranulation from human basophils and prevent clinical symptoms. In addition, EGCG and methylated EGCG were shown to have the ability to down-regulate Fc epsilon RI expression, and this suppressive effect may be due to a reduction of FcεRIα and γ mRNA levels.8,99,100) However, caution is needed for human application since EGCG has been identified as a causative agent in patients with green tea-induced asthma.101)
Theanine and γ-aminobutyric acid are also characteristic components of green tea. Using an in vivo brain microdialysis method, Yamada et al.102) demonstrated that theanine affects the release of neurotransmitters in the rat striatum. Recently, theanine was reported to enhance the synthesis of nerve growth factor and neurotransmitters during a nerve maturing period and promote maturation of the central nervous system.103) Electroencephalograms of volunteers who received 200 mg of theanine revealed the generation of α wave activity suggesting relaxation. γ-Aminobutyric acid is perhaps the most important inhibitory neurotransmitter in the brain, and its intake will affect brain functions. Thus, effects on brain function are a very important target for future investigations of green tea.