Neuroprotective and cognitive-enhancing potentials of herbal remedies: Focus on St. John's wort, green tea, and Ashwagandha.

Reading the Tea Leaves: Anticarcinogenic Properties of (-)-Epigallocatechin-3-Gallate

Reading the Tea Leaves: Anticarcinogenic Properties of (-)-Epigallocatechin-3-Gallate

We examined the anti-allergic effect of epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3″Me) and epigallocatechin-3-O-(4-O-methyl) gallate (EGCG4″Me) isolated from Japanese or Taiwanese tea (Camellia sinensis L.) leaves. These O-methylated catechins strongly inhibit mast cell activation and histamine release after Fc epsilon RI cross-linking through the suppression of tyrosine phosphorylation of cellular protein kinase (Lyn) and the suppression of myosin light chain phosphorylation and high-affinity immunoglobulin E (IgE) receptor expression via binding to the 67 kDa laminin receptor. A double-blind clinical study on subjects with Japanese cedar pollinosis or perennial allergic rhinitis was carried out. At 11 weeks after starting ingestion, during the most severe cedar pollen scattering period, symptoms (i.e. nose blowing and itchy eyes) were significantly relieved by "Benifuuki" green tea containing 34 mg/day of EGCG3″Me compared with a placebo "Yabukita" green tea that did not contain EGCG3″Me. One consecutive month of ingestion of "Benifuuki" green tea was useful for the reduction of some symptoms caused by Japanese cedar pollinosis and did not affect any normal immune responses in subjects with Japanese cedar pollinosis. In addition, the "Benifuuki" green tea was found to significantly relieve the symptoms of perennial rhinitis compared with the placebo "Yabukita" green tea. Based on the investigation of the effects of cultivars, tea crops, and manufacturing methods, green or semi-fermented teas made from fully-matured "Benifuuki" from the second crop should be consumed. The green tea components strictinins and theogallin showed anti-allergic action by inhibiting histamine release through suppressing the biosynthesis of IgE. It was reported that epigallocatechin (EGC) and polysaccharides in tea leaves had immunostimulating activities. Oral administration of a mixture with a high EGC ratio (1:2 to 3=epigallocatechin gallate (EGCG/EGC)) resulted in greater immunoglobulin A production by murine Peyer's patch cells. The EGCG/EGC ratio in a 4°C green tea extract was around 1:3 to 4, whereas in a 100°C extract, it was around 1:0.7. It was identified that EGC-induced phagocytosis can be blocked by catalase and an inhibitor of transient receptor potential melastatin 2. Moreover, it was found that a crude tea polysaccharide from immature tea leaves included a considerable amount of RNA as compared with that from mature tea leaves and increased the phagocytic activity in macrophage-like cells through Toll-like receptor 7.

Epigallocatechin gallate (EGCG) is the major active polyphenol in green tea. Protein interaction with EGCG is a critical step in the effects of EGCG on the regulation of various key proteins involved in signal transduction. We have identified a novel molecular target of EGCG using affinity chromatography, two-dimensional electrophoresis, and mass spectrometry for protein identification. Spots of interest were identified as the intermediate filament, vimentin. The identification was confirmed by Western blot analysis using an anti-vimentin antibody. Experiments using a pull-down assay with [3H]EGCG demonstrate binding of EGCG to vimentin with a Kd of 3.3 nm. EGCG inhibited phosphorylation of vimentin at serines 50 and 55 and phosphorylation of vimentin by cyclin-dependent kinase 2 and cAMP-dependent protein kinase. EGCG specifically inhibits cell proliferation by binding to vimentin. Because vimentin is important for maintaining cellular functions and is essential in maintaining the structure and mechanical integration of the cellular space, the inhibitory effect of EGCG on vimentin may further explain its anti-tumor-promoting effect.

Stroke is a condition that results from the obstruction or rupture of blood arteries in the brain, cutting off blood flow to the brain and causing the death of brain cells. Stroke is divided into two types based on the cause: ischemic stroke and hemorrhagic stroke. Ischemic stroke is the most common kind of stroke, accounting for around 87% of all strokes. The high occurrence of ischemic stroke has a wide-ranging influence on society. Because ischemic stroke still has a high prevalence and limited treatment options, a therapeutic breakthrough that can assist reduce mortality and morbidity from stroke, particularly ischemic stroke, is needed. Consuming green tea (Camellia sinensis), which has neurogenetic and neuroprotective benefits, is one of the advances that can be used. This literature was compiled through online searches using Pubmed, Sciencedirect, NIH NCBI, and Google Scholar instruments. It is known that green tea with the active ingredient Epigallocatechin-3-gallate (EGCG) has the potential to induce neurogenesis in ischemic conditions by inducing microglia to polarize to M2 and can inhibit pro-inflammatory mediators through inhibition of NOD-like Receptor Protein-3 (NLRP3) so that the pyroptosis process will also be inhibited, in this way EGCG also has the potential to become an ingredient that provides a neuroprotective effect. These two major processes will aid in the recovery of ischemic stroke patients.

Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo

The Effects of Green Tea on Obesity and Type 2 Diabetes

Scavenging of hydrogen peroxide and inhibition of ultraviolet light-induced oxidative DNA damage by aqueous extracts from green and black teas

We previously reported that catechins of green tea have different antiproliferative effects on cell lines derived from gender-dependent cancers; epicatechin 3-gallate (ECG) had the strongest inhibitory effect. In the present study, we examined the effects of epigallocatechin (EGC), epicatechin-gallate (ECG) and EGC 3-gallate (EGCG) on the viability, density, doubling time and cycle number of cell lines derived from melanoma metastasized to lymph nodes (MB-1133 and SE-0154) or distant organs (CH-0356, JK-0346, SA-1171, GE-0208, NS-1176 and LF-0023). These catechins have been documented to have no growth suppressive or apoptotic effects on normal melanocytes (Nihal et al., Int J Cancer 2005;114:513–21). EGCG (50 μM) showed greater inhibitory potency than EGC (50 μM) in SE-0154, NS-1176, GE-0208 and LF-0023 cell lines but the two catechins produced similar inhibitory effects in CH-0356, JK-0346 and SA-1171 cell lines. The IC50 (50% inhibitory concentration) was lower for EGC than EGCG in MB-1133 and CH-0356 cells, higher for EGC than EGCG in GE-0208 cells and comparable (11–12 μM) for both the catechins in LF-0023 cells. When compared with EGC, the cytotoxic effect (% dead cell counts) and the suppression of the growth (change in cell number) of all melanoma cell lines tested were pronounced with EGCG. This investigation validates the hypothesis that anticancer action of the various catechins may vary with the type of malignancy and provides a model for tumor cell heterogeneity based on susceptibility and resistance of tumor cells to different green tea catechins. Therefore, this information is critical for undertaking chemopreventive or chemotherapeutic trials against melanoma and gender-based cancers.

Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, mimics metabolic actions of insulin to inhibit gluconeogenesis in hepatocytes. Because signaling pathways regulating metabolic and vasodilator actions of insulin are shared in common, we hypothesized that EGCG may also have vasodilator actions to stimulate production of nitric oxide (NO) from endothelial cells. Acute intra-arterial administration of EGCG to mesenteric vascular beds isolated ex vivo from WKY rats caused dose-dependent vasorelaxation. This was inhibitable by L-NAME (NO synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), or PP2 (Src family kinase inhibitor). Treatment of bovine aortic endothelial cells (BAEC) with EGCG (50 microm) acutely stimulated production of NO (assessed with NO-specific fluorescent dye DAF-2) that was inhibitable by l-NAME, wortmannin, or PP2. Stimulation of BAEC with EGCG also resulted in dose- and time-dependent phosphorylation of eNOS that was inhibitable by wortmannin or PP2 (but not by MEK inhibitor PD98059). Specific knockdown of Fyn (but not Src) with small interfering RNA inhibited both EGCG-stimulated phosphorylation of Akt and eNOS as well as production of NO in BAEC. Treatment of BAEC with EGCG generated intracellular H(2)O(2) (assessed with H(2)O(2)-specific fluorescent dye CM-H(2)DCF-DA), whereas treatment with N-acetylcysteine inhibited EGCG-stimulated phosphorylation of Fyn, Akt, and eNOS. We conclude that EGCG has endothelial-dependent vasodilator actions mediated by intracellular signaling pathways requiring reactive oxygen species and Fyn that lead to activation of phosphatidylinositol 3-kinase, Akt, and eNOS. This mechanism may explain, in part, beneficial vascular and metabolic health effects of green tea consumption.

Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes.

Parkinson's disease (PD) is a common motor neurodegenerative disorder with multifactorial etiology that is an increasing burden on our aging society. PD is characterized by nigrostriatal degeneration which might involve oxidative stress, α-synuclein (αS) aggregation, dysregulation of redox metal homeostasis and neurotoxicity. Although the exact cause remains unknown, both genetic and environmental factors have been implicated. Among the various environmental factors tea consumption has attracted increasing interest, as besides being one of the most consumed beverages in the world, tea contains specific polyphenols which can play an important role in delaying the onset or halting the progression of PD. Green and black teas are rich sources of polyphenols, the most abundant being epigallocatechin-3-gallate (EGCG) and theaflavins. There is now consistent mechanistic data on the neuroprotective and neuroregenerative effects of tea polyphenols, indicating that they do not just possess anti-oxidant or anti-chelating properties but may directly interfere with aggregation of the αS protein and modulate intracellular signalling pathways, both in vitro and in animal models. EGCG in green tea has been by far the most studied compound and therefore future investigations should address more the effects of other polyphenols, especially theaflavins in black tea. Nevertheless, despite significant data on their potential neuroprotective effects, clinical studies are still very limited and to date only EGCG has reached phase II trials. This review collates the current knowledge of tea polyphenols and puts into perspective their potential to be considered as nutraceuticals that target various pathologies in PD.

Drug interaction of St John's wort with ciclosporin

Green tea supplementation produces better neuroprotective effects than red and black tea in Alzheimer-like rat model

Green tea is natural dried leaves of the tea plant, Camellia sinensis. This “nonfermented” tea contains more catechins than black tea (oxidized green tea) or oolong tea (partially oxidized tea). The composition of tea leaves depends on a variety of factors, including climate, season, horticultural practices, and the type and age of the plant. Green and black teas contain polyphenols, alkaloids (caffeine, theophylline, and theobromine), flavonols (quercetin, kaempferol, and rutin), amino acids, carbohydrates, proteins, chlorophyll, volatile organic compounds that contribute to tea flavonoid, fluoride, aluminum, minerals, and trace elements (Fig. 5.1). Green tea contains gallic acid (GA), chlorogenic acid, and caffeic acid, and flavonols such as kaempferol, myricetin, and quercetin (USDA data base 2003; Wang and Ho 2009). In contrast, black tea mostly has the polymerized catechins such as theaflavins and thearubigins. Collectively, these studies indicate that green tea is the source of catechins—simple flavonoids whereas black tea is rich in theaflavins and thearubigins, which are generated during the process of oxidation (USDA data base 2003; Wang and Ho 2009). Four major theaflavins have been identified from black tea, including theaflavin, theaflavin-3-gallate, theaflavin-3′-gallate, and theaflavin-3,3′-digallate. Catechins are strong antioxidants that can quench reactive oxygen species (ROS) such as super oxide radical, singlet oxygen, hydroxyl radical, peroxyl radical, nitric oxide, nitrogen dioxide, and peroxynitrite (Feng 2006). Since ancient times, green tea has been considered by the traditional Chinese and Japanese medicine as a healthful beverage. Human studies indicate that green tea not only contributes to a reduction in the risk of cardiovascular disease and some forms of cancer, but also induces antihypertensive effects by suppressing angiotensin I-converting enzyme, body weight control by suppressing the appetite, antibacterial, and antivirasic effects, solar ultraviolet protection, bone mineral density increase, antifibrotic effects, and neuroprotective effects. Green tea also decreases blood pressure (Henry and Stephens-Larson 1984) and blood sugar (Matsumoto et al. 1993). Lipid metabolism studies in animals, tissues, and cells have found that tea extract and catechins reduce triacylglycerol and total cholesterol concentrations (Nanjo et al. 1994; Chan et al. 1999), inhibit hepatic and body fat accumulation (Ishigaki et al. 1991), and stimulate thermogenesis (Dulloo et al. 2000). In addition, green tea boosts metabolism and improves immune function.