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Antioxidant Activity of Tea Polyphenols In Vivo: Evidence from Animal Studies
Abstract
Tea is particularly rich in polyphenols, including catechins, theaflavins and thearubigins, which are thought to contribute to the health benefits of tea. Tea polyphenols act as antioxidants in vitro by scavenging reactive oxygen and nitrogen species and chelating redox-active transition metal ions. They may also function indirectly as antioxidants through 1) inhibition of the redox-sensitive transcription factors, nuclear factor-kappaB and activator protein-1; 2) inhibition of "pro-oxidant" enzymes, such as inducible nitric oxide synthase, lipoxygenases, cyclooxygenases and xanthine oxidase; and 3) induction of phase II and antioxidant enzymes, such as glutathione S-transferases and superoxide dismutases. The fact that catechins are rapidly and extensively metabolized emphasizes the importance of demonstrating their antioxidant activity in vivo. Animal studies offer a unique opportunity to assess the contribution of the antioxidant properties of tea and tea polyphenols to the physiological effects of tea administration in different models of oxidative stress. Most promising are the consistent findings in animal models of skin, lung, colon, liver and pancreatic cancer that tea and tea polyphenol administration inhibit carcinogen-induced increases in the oxidized DNA base, 8-hydroxy-2'-deoxyguanosine. In animal models of atherosclerosis, green and black tea administration has resulted in modest improvements in the resistance of lipoproteins to ex vivo oxidation, although limited data suggest that green tea or green tea catechins inhibit atherogenesis. To determine whether tea polyphenols act as effective antioxidants in vivo, future studies in animals and humans should employ sensitive and specific biomarkers of oxidative damage to lipids, proteins and DNA.
... Berdasarkan kedua metode tersebut, diperoleh bahwa golongan senyawa flavonoid, vitamin E, vitamin C, alkaloid, tanin, dan saponin terkandung di dalam biji kluwak. Senyawa-senyawa polifenol ini memiliki aktivitas sebagai antioksidan yang secara molekuler dapat menetralisir radikal bebas yang ada didalam tubuh, anti-senesence atau anti-SASP (18) . Selain itu, ekstrak biji kluwak juga bersifat sebagai antimikroba sehingga sering digunakan untuk pengawet makanan (19) . ...
... Mekanisme Antioksidan dan Antisenescence pada Biji Kluwak. Pemberian antioksidan eksogen (luar tubuh) dan senyawa anti-SASP atau yang memiliki aktivitas senolitik dapat digunakan untuk mengatasi senescence (18) . Pemberian antioksidan sintetis seperti Butil Hidroksi Anisol (BHA) menyebabkan berbagai masalah kesehatan seperti tumor, kanker perut, dan kematian sel ginjal dan kandung kemih jika digunakan dalam jangka panjang (15). ...
... Pemberian antioksidan sintetis seperti Butil Hidroksi Anisol (BHA) menyebabkan berbagai masalah kesehatan seperti tumor, kanker perut, dan kematian sel ginjal dan kandung kemih jika digunakan dalam jangka panjang (15). Selain itu, pengobatan sintetis anti-SASP yang beraksi senolitik seperti dasatinib dan Bcl family inhibitors juga memiliki efek samping yang buruk (18). Oleh karena itu, diperlukan kandungan senyawa antioksidan yang poten dan anti-SASP alami dari bahan alam yang merupakan alternatif untuk mengatasi senescence. ...
Senescence merupakan kondisi yang menyebabkan disfungsi jaringan yang menyebabkan berbagai masalah seperti penuaan dini. Penuaan dini umumnya disebabkan oleh stres oksidatif yang berasal dari reaksi dalam tubuh maupun lingkungan (sinar UV, sinar X, dan radikal bebas). Biji kluwak (Pangium edule Reinw) mengandung berbagai senyawa antioksidan poten seperti: vitamin E, vitamin C, polifenol, flavonoid (kuersetin dan katekin), kuinin, dan β karoten. Narrative review ini bertujuan untuk mengungkap potensi kluwak sebagai agen antioksidan alami penghambat senescence. Metode pencarian literatur dengan teknik Booelan digunakan dengan menggabungkan beberapa kata kunci dengan notasi AND, OR, NOT dari berbagai literatur dari jurnal nasional maupun internasional yang diterbitkan dari berbagai database. Hasil yang diperoleh menunjukkan senyawa dalam biji kluwak dapat mencegah stres oksidatif penyebab senescence karena memiliki aktivitas antioksidan dari gugus fenolik dan ikatan rangkap terkonjugasi. Mekanisme yang dimiliki oleh biji kluwak, yaitu: menstabilkan ROS, meningkatkan enzim antioksidan dalam tubuh, menghambat enzim prooksidan, mencegah peroksidasi lipid, dan menghambat marker senescence (anti-SASP). Oleh sebab itu, kluwak berpotensi dikembangkan sebagai agen anti-senescence dalam bentuk sediaan kosmetika yang memiliki efek lokal, seperti hidrogel yang mudah dan aman digunakan dalam tubuh.
... Nevertheless, exceptional property of flavonoids including EGCG is their complex antioxidant action supplied by several mechanisms [74,75] (Figure 2). Direct antioxidant action of EGCG can be mediated by chelating free transition metals (iron, copper), which amplify the ROS formation [76,77]. Action of EGCG as a radical scavenger is related to its one-electron reduction potential, an ability to function as hydrogen or electron donor [78]. ...
... This means that antioxidants react with free radicals by two mechanisms: they can perform hydrogen atom transfer reaction (HAT), where the free radical removes one hydrogen atom from antioxidant, and the antioxidant itself becomes a radical, or the antioxidants perform the single electron transfer reaction (SET), where the antioxidant provides an electron to the free radical and itself then becomes a radical cation, where both reactions involve hydroxyl groups [79]. In particular, the presence of ortho-dihydroxyl group on the B and D rings and a galloyl moiety on the 3 position increases Direct antioxidant action of EGCG can be mediated by chelating free transition metals (iron, copper), which amplify the ROS formation [76,77]. Action of EGCG as a radical scavenger is related to its one-electron reduction potential, an ability to function as hydrogen or electron donor [78]. ...
... Antioxidant action of flavonoids is also related to induction of phase II detoxifying antioxidant enzymes, such as glutathione S-transferase (GST), NAD(P)H-quinone oxidoreductase, uridine diphospho(UDP)-glucuronosyl transferase or superoxide dismutase (SOD), which are responsible for elimination/deactivation of electrophilic forms of carcinogens or inactivation of ROS [51,77,101]. Glutathione (γ-glutamylcysteinylglycine, GSH) is the most abundant non-protein thiol protecting from oxidative stress; however, GSH participates in detoxification of xenobiotics and regulates many processes including cell proliferation, apoptosis, immune functions, and fibrogenesis. ...
(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that possesses a wide variety of actions. EGCG acts as a strong antioxidant which effectively scavenges reactive oxygen species (ROS), inhibits pro-oxidant enzymes including NADPH oxidase, activates antioxidant systems including superoxide dismutase, catalase, or glutathione, and reduces abundant production of nitric oxide metabolites by inducible nitric oxide synthase. ECGC also exerts potent anti-inflammatory, anti-fibrotic, pro-apoptotic, anti-tumorous, and metabolic effects via modulation of a variety of intracellular signaling cascades. Based on this knowledge, the use of EGCG could be of benefit in respiratory diseases with acute or chronic inflammatory, oxidative, and fibrotizing processes in their pathogenesis. This article reviews current information on the biological effects of EGCG in those respiratory diseases or animal models in which EGCG has been administered, i.e., acute respiratory distress syndrome, respiratory infections, COVID-19, bronchial asthma, chronic obstructive pulmonary disease, lung fibrosis, silicosis, lung cancer, pulmonary hypertension, and lung embolism, and critically discusses effectiveness of EGCG administration in these respiratory disorders. For this review, articles in English language from the PubMed database were used.
... The additional anti-tumor effects of EGCG result from its potent antioxidant action [39]. The direct antioxidant action of EGCG is mediated via scavenging ROS and chelating free transition metals [210]. Indirect antioxidant effects may be related to (1) inhibition of redox-sensitive transcription factors, such as NF-κB or AP-1; (2) inhibition of pro-oxidant enzymes, such as iNOS or COX-2; and (3) induction of antioxidant enzymes, such as glutathione S-transferase or superoxide dismutase (SOD) [40,210,211]. ...
... The direct antioxidant action of EGCG is mediated via scavenging ROS and chelating free transition metals [210]. Indirect antioxidant effects may be related to (1) inhibition of redox-sensitive transcription factors, such as NF-κB or AP-1; (2) inhibition of pro-oxidant enzymes, such as iNOS or COX-2; and (3) induction of antioxidant enzymes, such as glutathione S-transferase or superoxide dismutase (SOD) [40,210,211]. In addition, EGCG induces the expression of Nrf2 and associated enzymes HO-1 and NQO-1, contributing to its antioxidant and anti-inflammatory effects [172]. ...
(‒)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Thanks to multiple interactions with cell surface receptors, intracellular signaling pathways, and nuclear transcription factors, EGCG possesses a wide variety of anti-inflammatory, antioxidant, antifibrotic, anti-remodelation, and tissue-protective properties which may be useful in the treatment of various diseases, particularly in cancer, and neurological, cardiovascular, respiratory, and metabolic disorders. This article reviews current information on the biological effects of EGCG in the above-mentioned disorders in relation to molecular pathways controlling inflammation, oxidative stress, and cell apoptosis.
... Tea contains high antioxidants due to various polyphenols that can modulate oxidative stress in vivo, especially epigallocatechin-3-gallate, epicatechin-3gallate, theaflavins, and thearubigins. [149][150][151] Tea polyphenols can scavenge ROS and nitrogen species and chelate redox-active transition metal ions indirectly through: 149 (a) inhibition of nuclear factor-kB, redox-sensitive transcription factors, and activator protein-1, (b) inhibition of pro-oxidant enzymes such as inducible nitric oxide synthase, lipoxygenase, cyclooxygenase, and xanthine oxidase, and (c) induction of phase II and antioxidant enzymes such as glutathione S-transferases and superoxide dismutase. Chinese green tea has been shown to have antioxidant activity against H 2 O 2 , and O 2À . ...
... Green and black teas in animal models of atherosclerosis improved lipoprotein resistance to oxidation ex vivo. 149 Having demonstrated beneficial effects under those pathological conditions suggests that high antioxidant content in tea could also be very beneficial for healing chronic wounds. ...
Cellulose-based wound dressings are increasingly in demand due to their biocompatibility and extra-cellular matrix (ECM) mimicking properties. Although they contain no active constituents, pure cellulose-based scaffolds have promoted tissue regeneration. On the other hand, the absence of active ingredients opens the opportunity for the wound to become infected through microbial contamination and reactive oxygen, which will prolong the wound healing time. Microbial resistance to antibiotics has also become a problem that needs to be solved by replacing them using bioactive constituents of coffee and tea, which will be incorporated in a cellulose-based biopolymer matrix. Here, we discuss the potential development of a prospective wound dressing using cellulose composites with active ingredients found in coffee and tea. The mechanisms of coffee and tea wound healing properties are discussed, including their in vitro and in vivo characterization.
... Tea polyphenols, serving as antioxidants, perform various protective roles by scavenging reactive oxygen and nitrogen species, binding to transition metal ions, and stimulating antioxidant enzymes [3]. These actions contribute to safeguarding tissues, cells, and plasma from potential oxidative damage [4,5]. ...
Green tea is rich in catechins, particularly (−)-epigallocatechin-3-gallate (EGCG), which act as potent antioxidants and can help to prevent oxidative stress-related diseases. This article revealed the importance of green tea catechins in mitigating the risk of complex diseases such as cardiovascular disease, cancer, and neurological diseases. It also highlighted the potential side effects of excessive green tea consumption, emphasising the need for moderation. The review covered a wide range of potential health benefits of green tea, including its effects on weight loss, diabetes, metabolic syndrome, and cognitive decline. Additionally, the collection of research articles elaborated on the antioxidant and neuroprotective properties of green tea, as well as its potential role in preventing skin cancer and improving cognitive function. Overall, the evidence presented underscores the potential of green tea as a valuable dietary component in inhibiting diseases such as diabetes, cardiovascular, cancer, and infectious illness, while also emphasising the importance of green tea consumption in a balanced manner.
... Free radical scavenging by EGCG is linked to the presence of the gallate group in the 3-position and the trihydroxy B-ring structure (Khan and Mukhtar 2007). Moreover, EGCG protects cells and tissues from oxidative damage by inhibiting pro-oxidative enzymes such as xanthine oxidase, lipoxygenase, cyclooxygenase, and inducible nitric oxide synthase (Frei and Higdon 2003). ...
... This result is in conformity with the findings of Calixto et al. (1998) which stated that Phyllanthus niruri (Chanca piedra) is a good source of lignans, tannins, polyphenols, alkaloids, flavonoids, terpenoids and steroid. The protective effects of these phytochemicals have received more attention against free radical induced liver toxicities (Frei and Higdon, 2003). Flavonoids played an important role in the protection against oxidative stress, (Okada et al., 2001) especially in the case of cancer (Babich et al., 2005). ...
Oxidative stress has been recognized as a co-occurring pathogenic process that initiates and advances liver injury. Various risk factors, such as alcohol, drugs, environmental toxins, and irradiation, can cause the liver to experience oxidative stress, which in turn can lead to serious liver conditions such as alcoholic liver disease. This study was carried out to evaluate the antioxidant potentials of methanol leaf extract of Phyllanthus niruri Linn. (Chanca piedra). The sample was obtained from Maiduguri, Borno State, Nigeria. The methanol leaves extract was subjected to qualitative phytochemical analysis and in vitro radical scavenging activity, using standard laboratory procedures. The methanol leaves extract of Phyllanthus niruri Linn. (Chanca piedra) exhibited a significant antioxidant activity on both hydrogen peroxide (H2O2) and di-phenyl-picryl hydrazyl (DPPH) radical scavenging activity assay with IC50 values of 3.70±0.06 and 6.78±0.01 μg/ml respectively, as compared to the standard (Ascorbic acid) with IC50 values of 2.39±0.01 and 1.25±0.01 μg/ml, respectively. This study therefore suggests that the methanol leaves extract of Phyllanthus niruri Linn. (Chanca piedra) possessed antioxidant activity.
... (17) As an antioxidant, EGCG has also been shown to increase cell viability by decreasing reactive oxygen species. (18)(19)(20) Importantly, Kim et al. (21) found that EGCG was effective in preventing IL-8 production, which in turn, reduced the degree of inflammatory response. However, no studies to date have reported improved iron status by reducing inflammation. ...
Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocatechin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague–Dawley rats were fed an iron-deficient diet for 2 weeks and then randomly divided into four groups ( n 8 each): positive controls, negative controls, lipopolysaccharide (LPS, 0⋅5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet) for 3 additional weeks. The study involved testing two control groups, both treated with saline. One group (positive control) was fed a regular diet containing standard iron, while the negative control was fed an iron-deficient diet. Additionally, two treatment groups were tested. The first group was given LPS, while the second group was administered LPS and fed an EGCG diet. Iron status, hepcidin, C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS ( P = 0⋅02) and the LPS + EGCG ( P = 0⋅01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative control ( P < 0⋅001) but not with both LPS groups. SAA concentrations were significantly lower in the LPS + EGCG group compared to LPS alone group. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.
... Four kinds of catechins including (−)-epigallocatechin gallate (EGCG), (−)-epigallocatechin (EGC), (−)epicatechin gallate (ECG), and (−)-epicatechin (EC) are mainly classified, among which EGCG is the most abundant accounting for 59% of the total catechins [9,10]. These catechins have been reported to possess various physiological functions, such as antioxidative [11,12], anti-inflammatory [13,14], and antimicrobial properties [15,16]. ...
Epigallocatechin-3-gallate (EGCG) has been recognized as a potential additive for aquafeeds due to its beneficial biological functions. In order to evaluate the potential application of EGCG in Chinese rice field eel (Monopterus albus), six isonitrogenous and isolipidic diets containing 0, 25, 50, 100, 200, and 400 mg/kg EGCG were formulated and were fed to Monopterus albus (M. albus) for 9 weeks. The results showed that M. albus fed diets containing 0 and 100 mg/kg EGCG presented higher weight again and specific growth rate than the other groups. Fish fed with 25, 50, and 400 mg/kg EGCG displayed lower whole-body lipid content. Serum aspartate aminotransferase (AST) concentration significantly decreased in EGCG treated groups with the exception of 100 mg/kg group. Hepatic catalase (CAT) activity and glutathione (GSH) concentration decreased as EGCG level increased while malondialdehyde (MDA) concentration showed an opposite trend. EGCG supplementation resulted in a promoted lysozyme (LZM) activity and immunoglobulin M (IgM) level in the liver of M. albus. Furthermore, transcription of three immune related genes including major histocompatibility complex (mhc-2α), hepcidin, and interleukin-8 (il-8) mRNAs was upregulated by EGCG treatment; while transcription of interleukin-6 (il-6) and nuclear factor kappa-B (nf-kb) genes was downregulated. Results also showed a linear relation between EGCG inclusion level and parameters of AST, CAT, GSH, MDA, LZM, IgM, and immune-related genes transcriptions. In summary, it could be suggested that EGCG supplementation enhanced the nonspecific immune response of the Chinese rice field eel. Based on the broken-line regression analysis of IgM, the optimal dietary EGCG supplementation for M. albus was estimated to be 109.81 mg/kg.
... ECGC does not only exert protective effects in the central nervous system (CNS) but also mediates tissue damage because of its reaction with O2 -yielding NO -3 the ion that can nitrosylate tyrosine or cysteine residues in proteins 50 . The hydroxyl and trihydroxy (gallate) groups of EGCG appear important for scavenging physiologically relevant ROS/RNS ( fig.19) 51 . However, the use of EGCG is often hindered by problems such as its poor water solubility, rapid metabolism, and ready degradation in aqueous solutions. ...
To find a promising drug for treatment of Alzheimer’s` is not that easy target. Although some medications have FDA approval for management of AD, all of them offer symptomatic benefits. This is because efforts to find the treatment are distributed among many targets in the brain which make it so difficult to find a drug that can correct all of them at once. The primary histopathologic lesions of Alzheimer’s pathology are amyloid plaques, NFTs and neuronal loss with a wide genetic background which deteriorate the patient condition so rapidly. In the current article, we highlight some lead compounds that protect brain cells from undergoing this dark pathway or, which is more important, to stop deterioration and worsening of the case after starting of the disease. sex lead compounds of natural sources suggested as anti-AD drugs with brief discussion of each of them regarding its chemistry, physiochemical properties, mechanism of action, bioavailability, derivatives and method of synthesis. These natural extracts can be expected as lead compounds for design and synthesis of more effective derivatives as prophylactic treatment against Alzheimer’s. The aim of our review is to help to direct efforts to treat AD toward the prophylactic choice according to research results and scientific facts.
... For example, in dairy cows and laying hens (Ling et al., 2022), the polyphenolic compounds in green tea can scavenge various oxygen free radicals, including superoxide anion, singlet oxygen, peroxynitrite, and hypochlorous acid (Severino et al., 2009). They can also achieve antioxidant effects by reducing the expression of redox-sensitive transcription factors such as NF-κB and activator protein-1, inhibiting the activity of "pro-oxidant" enzymes, and increasing the activity of antioxidant enzymes such as GSH-Px (Frei and Higdon, 2003). In this study, the addition of DTR significantly increased the concentrations of T-SOD, GSH-Px, and CAT, indicating that DTR has significant antioxidant activity in sheep. ...
Ruminant animals face multiple challenges during the rearing process, including immune disorders and oxidative stress. Green tea by-products have gained widespread attention for their significant immunomodulatory and antioxidant effects, leading to their application in livestock production. In this study, we investigated the effects of Dried Tea Residue (DTR) as a feed additive on the growth performance, blood biochemical indicators, and hindgut microbial structure and function of Hu sheep. Sixteen Hu sheep were randomly divided into two groups and fed with 0 and 100 g/d of DTR, respectively. Data were recorded over a 56-day feeding period. Compared to the control group, there were no significant changes in the production performance of Hu sheep fed with DTR. However, the sheep fed with DTR showed a significant increase in IgA ( p < 0.001), IgG ( p = 0.005), IgM ( p = 0.003), T-SOD ( p = 0.013), GSH-Px ( p = 0.005), and CAT ( p < 0.001) in the blood, along with a significant decrease in albumin ( p = 0.019), high density lipoprotein ( p = 0.050), and triglyceride ( p = 0.021). DTR supplementation enhanced the fiber digestion ability of hindgut microbiota, optimized the microbial community structure, and increased the abundance of carbohydrate-digesting enzymes. Therefore, DTR can be used as a natural feed additive in ruminant animal production to enhance their immune and antioxidant capabilities, thereby improving the health status of ruminant animals.
... Tea is a common beverage throughout the world. In the current investigation, it was found that GT has an antioxidant effect in rats (30,31). Our findings demonstrated that GT intake reduced MDA concentration in addition, the results suggested that treatment with GT diminished lipid peroxidation and oxidative stress in experimental rats. ...
Green tea (GT) is believed to have antioxidant properties and beneficial effects on the treatment of some diseases. However, few findings were found concerning the impact of GT on oxidative stress. In the present study, the protective influence of GT against the oxidative stress caused by hydrogen peroxide (H2O2) in rats was evaluated. The research groups included a control (Con) group and five groups supplemented with 10g GT(G1), 20g GT(G2), 1% H2O2(P), 1% H2O2and10g GT (GP1), as well as 1% H2O2 and 20g GT(GP2). The effects of GT and H2O2 administration on serum biochemical parameters, such as lipid profile, malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) were assessed. The findings of this research revealed that the usage of GT lowered the level of cholesterol, triglyceride, LDL, MDA, Ox-LDL and coronary risk index. Moreover, an increase in high-density lipoprotein and very-low-density lipoprotein (VLDL) was observed in subjects who received GT, compared to the rats of the P group. The baseline lipid profile and GT consumption with or without H2O2 were the same between the Con and GT-treated groups. Therefore, GT usage was found to be advantageous in reducing Ox-LDL and lipid peroxidation in rats. These results confirm the traditionally claimed benefits of GT for protection against lipid peroxidation and atherosclerosis.
... Due to their distinctive antioxidant, anti-inflammatory, anticancer, and antibacterial properties, polyphenols have a special function in enhancing general health status [72,89,90]. Frei and Higdon [91] state that tea polyphenols are strong antioxidants that can directly chelate transition metals or scavenge reactive oxygen species. Additionally, smallmolecule polyphenols appear as attractive study topics as effective coronavirus treatments [92]. ...
Global production of the two major poultry products, meat and eggs, has increased quickly. This, in turn, indicates both the relatively low cost and the customers' desire for these secure and high-quality products. Natural feed additives have become increasingly popular to preserve and enhance the health and productivity of poultry and livestock. We consume a lot of polyphenols, which are a kind of micronutrient. These are phytochemicals with positive effects on cardiovascular, cognitive, anti-inflammatory, detoxifying, anti-tumor, anti-pathogen, a catalyst for growth, and immunomodulating functions, among extra health advantages. Furthermore, high quantities of polyphenols have unknown and occasionally unfavorable impacts on the digestive tract health, nutrient assimilation, the activity of digestive enzymes, vitamin and mineral assimilation, the performance of the laying hens, and the quality of the eggs. This review clarifies the numerous sources, categories, biological functions, potential limitations on usage, and effects of polyphenols on poultry performance, egg composition, exterior and interior quality traits.
... Medicinal plants, as well as herbal medicines derived from them, are becoming extremely popular in treating a large number of clinical conditions. As a result, interest in the therapeutic potential of plant products or medicinal plants in the treatment of chemically induced toxicity has increased significantly [11]. Several medicinal plants provided significant safeguards against arsenic toxicity in animal models that had been experimentally induced. ...
Arsenic toxicity is a major public health concern on a global scale, affecting hundreds of thousands of people. Arsenic contamination of drinking water is due to the leaching of arsenic into groundwater from sources of natural geological origin. Additionally, it is possible for it to occur as a result of mining and other industrial activities. Arsenic poisoning alters the parameters of haematology, biochemistry, and oxidative stress, and it results in tissue damage, which is localized mostly in the liver and kidney. However, due to the lack of effective medications, treating arsenic-mediated illnesses remains difficult. In recent years, indigenous plant-based treatments have been revealed to give effective and gradual recovery from arsenic-mediated toxicity while causing no adverse effects on the patient. Furthermore, it has been demonstrated that these plant-based interventions eliminate arsenic from the biological system. This might make them more effective than typical treatment drugs in addressing arsenic-mediated adverse effects in particular situations. The purpose of this study is to bring together experimental data on medicinal plants that have been shown to have anti-arsenic toxicity properties. In this review of the literature, it was shown that 15 medicinal plants provided considerable protection against arsenic poisoning in pre-clinical experiments.
... Common flavonoids include quercetin, kaempferol, and luteolin. Terpenes are volatile compounds that are derived from plants and are known for their anti-inflammatory, antimicrobial, and antispasmodic activities [12,13]. Common terpenes include limonene, linalool, and eugenol. ...
Several Premna species can be found over the entire tropical and subtropical regions of Australia, Asia, and Africa. Many conventional herbal preparations using P. integrifolia (Lamiaceae) have been reported for their potential health advantages. The P. integrifolia is taxonomically ambiguous because of the wide variation in specimens obtained from various geographic locations. The plant is extensively used to treat immune-related disorders, skin conditions, inflammatory conditions, and stomach issues. The root of P. integrifolia is broadly utilized in the manufacture of Ayurvedic pharmaceutical products, such as Dasamula Kvatha and Chayawanprash Avaleha. It has also been identified to have antibacterial, hepatoprotective, and antifungal properties. The current study aims to investigate the antioxidant and cytotoxic activity of P. integrifolia against various cancers, as well as its antiinflammatory activity, antidiabetic, cardiac-stimulant, anti-obesity, hepatoprotective, immunomodulatory, analgesic, antiarthritic, antiparasitic, and wound healing activity, as well as the presence of various secondary metabolites in different parts of the plant used in a variety of formulations.
... The biochemical significance of natural antioxidants gained a great deal of attention in biological system against several toxic free radicals. (43,44) Any molecule found at a low concentration, inhibits the oxidative reaction cycle by eliminating the free radical precursor is called antioxidant agent. Yet both plants and animals continue to have complicated systems that contain various kinds of antioxidants (45) . ...
... Los frutos maduros contienen menos cantidad de alcaloides (solanina) (Saijo, 1982;Son, 2003), lo cual queda confirmado en el estudio fitoquímco realizado a nuestro extracto (Tabla 1), donde se demuestra la presencia de una abundante cantidad (+++) de compuestos fenólicos, regular cantidad(++) de flavonoides y poca cantidad (+) de taninos, alcaloides, esteroides triterpénicos y glicósidos Los flavonoides, presentan actividad sobre el sistema vascular como aumento de la permeabilidad y disminución de la resistencia de los capilares sanguíneos, actuan inhibiendo distintos sistemas enzimáticos relacionados con la funcionalidad de los vasos (hialuronidasa, catecol-O-metiltransferasa, fosfodiesterasa-AMPc, PKC, etc). Además, poseen actividad antiagregante plaquetaria, antiinflamatoria y captadora de radicales libres (Fujisawa, 2002;Frei, 2003); así como los antocianósidos, poseen actividad antiinflamatoria, antiagregante plaquetaria además de ser empleados en oftalmología durante el tratamiento de trastornos circulatorios a nivel de la retina, así mismo los compuestos fenólicos han demostrado tener actividad antioxidante (Zheng, 2001, Tsuda, 2000Cristoni, 1987). Por tal motivo se podría inferir que el extracto acuoso del fruto de hierba mora tiene propiedades antiulcerosas y citoprotectora (Aguwa, 1998). ...
... As an antioxidant, EGCG has also been shown to increase cell viability by decreasing reactive oxygen species [18][19][20]. Importantly, Kim et al. [21] found that EGCG was effective in preventing IL-8 production, which in turn, reduced the degree of inflammatory response. However, no studies to date have reported improved iron status by reducing inflammation. ...
Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.
... The pioneering report on the anti-oxidative activity of tea polyphenols in animals by Frei and Higdon (2003) sparked much research on improving the health value of milk by increasing polyphenol contents. Dietary enrichment of milk in plant phenolics and their residues was reported by Di Trana et al. (2015) and Cabiddu et al. (2019) in goats, and by Besle et al. (2010) in cows. ...
... Other natural antioxidants such as caffeine, melatonin, flavonoids, J Cell Signal. 2023 Volume 4, Issue 1 16 polyphenols, and phytochemicals (e.g., albana) help decrease radiation-induced damage in either plasmid or cellular DNA through scavenging of oxygen radicals and/or peroxides [37][38][39][40][41][42]. Several investigations revealed that those who take probiotics throughout their radiotherapy for various types of cancer are less likely to experience radiation-induced diarrhea [43][44][45]. ...
Ionizing radiation has been indispensable to medical diagnosis. In cancer, radiation therapy or radiotherapy (RT) offers patients a better chance of survival. It destroys cancer by depositing high-energy radiation on the cancer tissues, though it may directly damage a few normal cells. Therefore, the total radiation dose is administered in fractionated modalities over weeks or months. However, experimental evidence indicates that the irradiated cancer cells subsequently release cytokines in the blood that enter into nearby unirradiated nuclei/cells through several signaling pathways and cause radiation-induced bystander effects (RIBEs) such as DNA damage, chromosomal instability, mutation, and apoptosis in them as side effects of RT. Recently, many combined therapeutic protocols consisting of a few natural and synthetic products have been proposed to minimize RIBEs. This article reviews the present understanding of RIBEs and their possible countermeasures. Besides, a new protocol of combined therapy of nanoparticle-based ion treatment (NIT) and RT to minimize RIBEs has been proposed.
... Polyphenol extracts from natural food sources such as tea, coffee, cacao are known to exhibit antioxidant and antitumor activity [5,6]. In particular, cinnamic acid and its derivatives found in the plant Cinnamomum zeilancium [7], are also known to display anticancer activity. ...
Recent studies have shown that Ephrin receptors may be upregulated in several types of cancers including breast, ovarian and endometrial cancers, making them a target for drug design. In this work, we have utilized a target-hopping approach to design new natural product-peptide conjugates and examined their interactions with the kinase-binding domain of EphB4 and EphB2 receptors. The peptide sequences were generated through point mutations of the known EphB4 antagonist peptide TNYLFSPNGPIA. Their anticancer properties and secondary structures were analyzed computationally. Conjugates of most optimum of peptides were then designed by binding the N-terminal of the peptides with the free carboxyl group of the polyphenols sinapate, gallate and coumarate, which are known for their inherent anticancer properties. To investigate if these conjugates have a potential to bind to the kinase domain, we carried out docking studies and MMGBSA free energy calculations of the trajectories based on the molecular dynamics simulations, with both the apo and the ATP bound kinase domains of both receptors. In most cases binding interactions occurred within the catalytic loop region, while in some cases the conjugates were found to spread out across the N-lobe and the DFG motif region. The conjugates were further tested for prediction of pharmacokinetic properties using ADME studies. Our results indicated that the conjugates were lipophilic and MDCK permeable with no CYP interactions. These findings provide an insight into the molecular interactions of these peptides and conjugates with the kinase domain of the EphB4 and EphB2 receptor. As a proof of concept, we synthesized and carried out SPR analysis with two of the conjugates (gallate-TNYLFSPNGPIA and sinapate-TNYLFSPNGPIA). Results indicated that the conjugates showed higher binding with the EphB4 receptor and minimal binding to EphB2 receptor. Sinapate-TNYLFSPNGPIA showed inhibitory activity against EphB4. These studies reveal that some of the conjugates may be developed for further investigation into in vitro and in vivo studies and potential development as therapeutics.
Graphic Abstract
... The mechanism by which EGCG inhibits RNS accumulation is not fully understood, although many of the structural antioxidant properties contributing to the scavenging of ROS may play a similar role here. Alternatively, this may be linked to other antioxidant properties of EGCG, such as the inhibition of pro-oxidant compounds important in the signaling cascade that produces NO [80]. ...
Simple Summary
Green tea is a popular beverage worldwide and has shown to be beneficial in the treatment of different cancers. However, its role in the treatment of reproductive cancers remains controversial. This review aims to summarize the data available in the literature about the role of green tea in treating gynecological cancers. Examination of available evidence may provide a better understanding of the green tea benefits and focus future research related to this topic.
Abstract
Green tea originates from the tea plant Camellia sinensis and is one of the most widely consumed beverages worldwide. Green tea polyphenols, commonly known as catechins, are the major bioactive ingredients and account for green tea’s unique health benefits. Epigallocatechin-3-gallate (EGCG), is the most potent catechin derivative and has been widely studied for its pro- and anti-oxidative effects. This review summarizes the chemical and chemopreventive properties of green tea in the context of female reproductive cancers. A comprehensive search of PubMed and Google Scholar up to December 2022 was conducted. All original and review articles related to green tea or EGCG, and gynecological cancers published in English were included. The findings of several in vitro, in vivo, and epidemiological studies examining the effect of green tea on reproductive cancers, including ovarian, cervical, endometrial, and vulvar cancers, are presented. Studies have shown that this compound targets specific receptors and intracellular signaling pathways involved in cancer pathogenesis. The potential benefits of using green tea in the treatment of reproductive cancers, alone or in conjunction with chemotherapeutic agents, are examined, shedding light on new therapeutic strategies for the management of female reproductive cancers.
... Moreover, those infusions had less catechins, particularly galloylated-catechins, and lower antioxidant capacity. 22 The boron element in the iron-based amorphous film reacts with flavonoids and anthocyanins in the polyphenol solution to generate naphthoquinone derivatives of organic boride. The polyphenols in the solution decrease and the color becomes darker, and the pH value increases from 5.5 to 6.5 within 50 min. ...
It is challenging to convert the superhydrophobic surfaces of iron-based amorphous films into hydrophilic surfaces through surface treatment. In this study, a novel, environmentally friendly method is used to change the superhydrophobic surfaces of Fe78Si13B9 amorphous alloy films, which include their rougher and smoother surfaces. The boron element in the films reacted with the flavonoids and anthocyanins in the solution to create organic conversion membranes and organic boronizing naphthoquinone derivatives on the surfaces of the films when they were dipped in tea polyphenol aqueous solution at 80 °C for 60 min. On the rougher surface and the smoother surface, the organic conversion membranes had thicknesses of about 10 and 3 μm, respectively. When iron-based amorphous alloy films were employed as soft magnetic materials to create electronic and electrical devices, the packaging issue caused by low wettability with epoxy resin had been resolved because both the side surfaces of modified films had good wettability with epoxy resin. In addition, the magnetic surface effect of modified films was significant. After surface treatment, the inductance value of the film decreased by more than 25%. The magnetic surface effect of iron-based amorphous films can be applied to the preparation of tea sensors, and the sensor can achieve the "one to one" high precision test of "one tea curve". The magnetic surface effect of the film provides a quick, simple, lower cost, and strong anti-interference idea for the rapid detection of tea polyphenols.
... Present in C. album berries, neochlorogenic [37,39,40], p-hydroxybenzoic [24], and ferulic [28,29] acids seem to be able to inhibit NF-κB activation. In addition, several flavonols such as catechins [66][67][68][69], quercetin rhamnosyl hexoside [78][79][80], myricetin [74,75], procyanidins [72,73] and kaempherol hexoside [76], identified in C. album leaves have been shown to suppress NF-κB transcriptional activity and, thus, can prevent inflammation and carcinogenesis. ...
Corema (C.) album belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. C. album berries have been used for centuries in traditional medicine. Recent studies have revealed that not only the berries but also the leaves have relevant antioxidant, antiproliferative, and anti-inflammatory properties, bringing this plant to the forefront of discussion. A systematic review of the literature was carried out to summarize the phenolic compounds and bioactive properties identified in C. album berries and leaves and to search for research gaps on this topic. The search was conducted in three electronic databases (PubMed, SCOPUS, and Web of Science) using PRISMA methodology. The inclusion criteria were the chemical compositions of the berries, leaves, or their extracts and their bioactive properties. The exclusion criteria were agronomic and archaeological research. The number of studies concerning phenolic compounds’ composition and the bioactive properties of C. album berries and leaves is still limited (11 articles). However, the variety of polyphenolic compounds identified make it possible to infer new insights into their putative mechanism of action towards the suppression of NF-kB transcription factor activation, the modulation of inflammatory mediators/enzymes, the induction of apoptosis, the modulation of mitogen activated protein kinase, cell cycle arrest, and the reduction of oxidative stress. These factors can be of major relevance concerning the future use of C. album as nutraceuticals, food supplements, or medicines. Nevertheless, more scientific evidence concerning C. album’s bioactivity is required.
... The IR spectra of CTS modified with other polyphenols contents (10 wt.%, 15 wt.% and 20 wt.%) are similar to the IR spectrum of CTS-PP5, thus, we do not show their IR spectra and only list the wavenumbers of some functional group vibrations in modified CTS in table 1. It can be seen that the difference in wavenumbers of these samples is not much, therefore, the content of polyphenols has a negligible effect on the structure of modified CS. [29,30] The CS modified with different contents of PP has antioxidant ability lower than PP but higher than CTS. This is a general trend for the materials hybrid of PP with CTS although CTS has also antioxidant activity. ...
This paper presents the modification of chitosan with polyphenols and application the modified chitosan in storage of tomatoes fruits. The ascorbic acid was used as a initiator for the modification reaction. The content of polyphenols was varied from 5 to 20 wt. % in comparison with chitosan weight. Some methods and techniques were used to characterize chitosan and modified chitosan including to infrared (IR) spectroscopy, DPPH assay and inhibition zone diameter by diffusion agar. The obtained results showed that chitosan was modified successfully with polyphenols. The modified chitosan samples have good antioxidant activity and against to E. coli, S. aureus and C. albicans. Based on the antioxidant activity and antimicrobial activity results, the most suitable content of polyphenols was found at 10 wt.%. The chitosan modified with 10 wt.% of polyphenols in a combination with nano Ag solution exhibits a significant efficiency on preventing the weight loss as well as remaining color, the firmness, and the soluble solids content (SSC) of tomato fruits during 20 days of testing. Moreover, the modified chitosan/nano Ag also has a great ability in inhibiting the growth of microbial on the skin of tomatoes during post-harvesting storage.
... Oxidative stress plays a major role in diabetic vascular complications through autoxidation of glucose and glycosylation of proteins. Lipid peroxidation is considered to be the hallmark of oxidative stress, in which reactive oxygen species interact with polyunsaturated fatty acids, and leads to the formation of lipid products which then cause damages to the membrane components of the cell (Kumar et al., 2008;Frei and Higdon, 2003). Today, extensive evidences have been demonstrated that thiobarbituric acid reactive substances level is increased in both plasma and aortic tissue accompany with defective vascular endothelial function of experimental diabetic models (Alper et al., 2006;Ozansoy et al., 2001). ...
The present study was designed to investigate the beneficial role of diosgenin on oxidative stress markers and histopathological changes in aorta of streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal injection of streptozotocin (55 mg/kg body weight (b.w.)). From the sixth week, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for 4 weeks. At the end of the experimental periods, diabetic rats exhibited significant increase in the levels of plasma glucose, glycosylated hemoglobin with significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in aortic tissues of diabetic rats. Oral administration of diosgenin to diabetic rats significantly decreased the plasma glucose and increased the insulin level based on a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings suggest that diosgenin could have a beneficial role against aortic damage induced by oxidative stress in diabetic state, which was evidenced by the propensity of diosgenin to modulate the antioxidant defense and to decrease the lipid peroxidation in aorta.
... Numerous studies have shown that poor-grade tea, broken tea, tea powder, tea waste and other tea by-products are feasible additives for animal feed for dairy cows, pigs, chickens, goats, sheep, cattle, and mice (Afsharmanesh and Sadaghi, 2014;Alagawany et al., 2020;Biswas et al., 2000;Frei and Higdon, 2003;Shomali et al., 2012;Uuganbayar et al., 2005;Yang et al., 2003;Zhou et al., 2016). The milk yield of dairy cows was increased by more than 10 % when 1 % broken oolong tea was added to feed (Yueqin et al., 2019). ...
This study explored the protective effect of broken tea on growth, antioxidant capacity, nutritional composition and lipid metabolism in fish fed a high-fat (HF) diet. A total of 450 Cyprinus carpio (18.79 ± 3.16 g) were divided into five groups and fed for 8 weeks: the control diet group (C), HF diet group (HF), and the HF diet plus 1 %, 2 % and 3 % broken Xinyang Maojian tea (BTMaojian) groups (HF+1%BT, HF+2 %BT and HF+3 %BT). We found that the weight gain rate (WGR) of carp was increased significantly in the HF+ 3 %BT group compared with the control group (P < 0.05). The elevated hepatic malondialdehyde (MDA), alanine aminotransaminase (ALT), aspartate aminotransferase (AST), and triglyceride (TG) in the HF group were attenuated by BTMaojian treatment (P < 0.05). Moreover, the low total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) content in serum and hepatopancreas in the HF group were significantly increased by the addition of BTMaojian (P < 0.05). The total essential amino acid content in muscle was significantly increased in the HF+ 2%BT group compared with the HF group (P < 0.05). Additionally, the highest linoleic acid content in muscle was found in the HF+ 3%BT group. The excessive hepatopancreas fat accumulation caused by the HF diet was alleviated in the 2 % and 3 % BTMaojian supplementation groups. The mRNA level of most key lipid metabolism genes in the hepatopancreas, intestinal tract, muscle and adipose tissue tended to be increased in the HF group and decreased in the BTMaojian treatment groups. Taken together, these results indicated that the addition of 2 % or 3 % BTMaojian likely positively affected growth performance, enhanced flesh quality, and alleviated harmful symptoms, including low antioxidant capacity and excessive hepatic fat accumulation in carp fed a HF diet. Thus, BTMaojian can be used as a green feed additive in C. carpio feed.
... Tea contains a wide range of substances, particularly polyphenols, and several studies have demonstrated that these substances lower the risk of a number of illnesses. In terms of natural polyphenols, green tea extract is the most abundant source [18,19]. Polyphenols in green tea have been extensively studied for their potential benefits, such as antibacterial, antimutagenic, and anticancer properties [20]. ...
Polyphenon 60 (PP60) from green tea has long been used as an antioxidant, anticancer, antimicrobial, and antimutagenic. Aim of the Study. To investigate tyrosinase inhibition-related kinetic mechanism and antimelanogenesis potential of PP60. Materials and Methods. The effect of PP60 on melanin and tyrosinase was evaluated in A375 melanoma cells and zebrafish embryos. The melanoma cells were treated with 20, 40, and 60 µg/mL of PP60, and tyrosinase expression was induced by using L-DOPA. The western blot method was used for the evaluation of tyrosinase expression. Cell lysates were prepared from treated and untreated cells for cellular tyrosinase and melanin quantification. Furthermore, zebrafish embryos were treated with 20, 40, and 60 µg/mL of PP60 and reference drug kojic acid for determination of depigmentation and melanin quantification. In vitro assays were also performed to examine the impact of PP60 on mushroom tyrosinase activity. To determine cytotoxicity, MTT was used against melanoma cell line A375. Results. PP60 showed good tyrosinase inhibitory activity with an IC50 value of 0.697 ± 0.021 µg/mL as compared to kojic acid a reference drug with an IC50 value of 2.486 ± 0.085 µg/mL. Kinetic analysis revealed its mixed type of inhibition against mushroom tyrosinase. In addition, western blot analysis showed that at 60 µg/mL dose of PP60 significantly reduced L-DOPA-induced tyrosinase expression in melanoma cells. PP60 significantly inhibits the cellular tyrosinase () and reduces the melanin () contents of melanoma cells. Furthermore, PP60 was found to be very potent in significantly reducing the zebrafish embryos’ pigmentation () and melanin () content at the dose of 60 µg/mL. Conclusions. Our results demonstrate that PP60 has a strong potency to reduce pigmentation. It may be useful for the cosmetic industries to develop skin whitening agents with minimal toxic effects.
The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.
Contaminant-induced harmful effects are a global concern. Liver is the main
site of xenobiotic metabolism and plays a vital role in averting accumulation of a wide
range of compounds by converting them into a form suitable for elimination. Phase I
drug metabolizing enzymes, primarily cytochrome P450s carry out bioactivation of
carcinogens, thus converting them into electrophilic species which are genotoxic and
cytotoxic. These reactive intermediates form protein adducts and induce DNA and
RNA damage. Phase II drug metabolizing enzymes, such as glutathione-S-transferases,
UDP-glucuronosyl transferases, sulfotransferases and N-acetyltransferases detoxify the
reactive electrophilic species by conjugating these hydrophobic intermediates to a
water-soluble group, thus masking their reactive nature and allowing subsequent
excretion. Beneficial effects of natural dietary compounds in detoxification and
elimination have been demonstrated in various studies. They have been reported to be
effective in inhibiting chemically-induced carcinogenesis. Phytochemicals are known
to influence the biotransformation of xenobiotics and may play an important role in
reducing their toxicity and carcinogenicity. Indoles, isothiocyanates, allium
organosulfur compounds, flavonoids, phenolic acids, terpenoids and psoralens may
alter the levels of Phase I and Phase II drug metabolizing enzymes by affecting the
transcriptional rates of their genes, the turnover rates of specific mRNAs or enzymes or
the enzyme activity by inhibitory or stimulatory actions. Agents that preferentially
activate Phase II over Phase I enzymes are considered as promising chemopreventives.
Phase I metabolism involves oxidation, reduction or hydrolysis reactions via
cytochrome P450 enzymes and lead to the conversion of drugs to more polar (water
soluble) active metabolites by unmasking or inserting a polar functional group such as
-OH, -SH and –NH2. Xenobiotics metabolized via Phase I reactions have longer halflives.
Phase II metabolism involves conjugation reactions such as glucuronidation,
acetylation and sulfation. Conjugation reactions increase water solubility of drug by
adding a polar moiety thus converting them into water soluble inactive metabolites.
The present book chapter discusses the interaction between phytochemicals and xenobiotic metabolizing enzymes in detoxification of harmful exogenous compounds
which have been implicated in carcinogenesis.
The latex, leaves, stems, and roots of Euphorbia tithymaloides (Euphorbiaceae) have traditionally been used to treat earaches, insect stings, ringworm, toothaches, skin cancer, umbilical hernia, and warts. Approximately 1 kg of the pulverized leaves was macerated successively with hexane and ethyl acetate, and resultant Crude extracts were phytochemically screened using standard established procedures. Ethyl acetate extract was loaded onto a column containing slurry of silica gel. Gradients of hexane in ethyl acetate mobile phase were used to elute the column, affording a total of 130 fractions. Fractions 41-47 gave tiny deposit on evaporation labelled UMPT (m.p: 269-270 oC).Their thin layer chromatography gave a single spot of Rf 0.61.These were combined and labelled UMPT44. Phytochemical screening of UMPT44 gave positive test for phenols and triterpenoids. Antimicrobial screening of UMPT44 showed that it was active against some fungi and bacteria. The zone of inhibition measured 30 mm when tested against Coniophora puteana, 29 mm against methicillin-resistant Staphylococcus aureus, 27 mm against Salmonella typhi, and 26 mm against Staphylococcus aureus, Fusarium oxysporum, and Escherichia coli. Additionally, there was a 25 mm zone of inhibition against Serpula lacrymans. The determination of minimum inhibitory concentration and minimum bactericidal/fungicidal concentration indicated that UMPT44 holds promise as a potential antimicrobial agent. Based on evaluation of NMR spectral data and comparison with literature reports, UMPT44 was identified as cycloeucalenol transferulate. This is the first time this compound is isolated from the plant
Bicomponent (PET/PTT) filaments have excellent elastic recovery, elasticity, thermal comfort, etc., which make them appropriate for use in sports clothing. As they are dyed with chemical dyestuffs, it could cause a great harm to human health. In this context, this paper investigates the possibility of dyeing PET/PTT with a natural colorant obtained from date palm pits (DPP). This natural dye showed, in our previous studies, very good results for dyeing cotton. The extracted solution was characterized and its chemical constitution, antioxidant activity, and GC/MS study were investigated and discussed. Knitted fabrics consisting of 100% bicomponent (PET/PTT) filaments were used for dyeing with the aqueous extract. The influence of the dyeing parameters on the value of the color yield (\(\sum \left(\frac{K}{S}\right)\)) and the colorimetric \(\left({L}^{*};{a}^{*};{b}^{*};{C}^{*};h\right)\) coordinates was evaluated and analyzed. The studied parameters were the dyebath pH, temperature, and the duration of dyeing. The color fastnesses of dyed fabrics were also analyzed and improved using bio-based adjuvants. The obtained results indicated that the optimum dyeing conditions (pH = 5, temperature = 100 °C, duration = 60 min) led to the best value of color yield. Moreover, excellent wash and sweat fastness values (in the range of 4–5) were found. The GC/MS study of acetonic extract powder of date palm pits revealed the phenolic groups responsible for the coloring of the polyester fibers and confirmed the presence of certain compounds having antifungal, antibacterial, antioxidant, and anticancer activities.
The antioxidant activity of tea leaves extract is a widely researched topic. Tea leaves, particularly those from the Camellia sinensis Linn plant, have garnered attention due to their potential health benefits attributed to their antioxidant properties. Antioxidants are compounds that can neutralize harmful free radicals in the body, which can damage cells and contribute to various health issues, including cancer, cardiovascular diseases, and aging. In this research, the matured tea leaves which has been considered as agricultural waste in Moulovibazar area of Bangladesh have been investigated as a potential source of antioxidant. Methanol was used as solvent for the extraction of antioxidant. DPPH (1,1-diphenyl-2-picryl hydrazyl) scavenging free radical assay method was used to assess the antioxidant activity of the extracts and ascorbic acid was used as positive control. Gas chromatography with mass spectrometric (GC-MS) analysis method was conducted on this extract to investigate the principal components. The half inhibitory concentration (IC50) values of methanol extract and ascorbic acid were found to be 69.51 μg/mL and 10.70 μg/mL, respectively. Caffeine is the main compound (74.47%) among the eight bioactive compounds was identify and quantified by GC-MS.
Полифенолы – продукты вторичного метаболизма растений, широко применяемые в качестве биологически активных соединений в фармакологии, медицине, сельском хозяйстве. Эти соединения встречаются во всех органах самых различных растений (плоды, семена, корни, кора, древесина, листья). Все растительные полифенолы по отношению к животным организмам в той или иной степени обладают биологической активностью широкого спектра, являясь важной составной частью рациона питания и в настоящее время находятся в центре научного внимания. Различные растительные полифенолы – обязатель- ный компонент любой диеты, включающей растительные продукты, и суточное потребление их при обычной диете в среднем составляет не менее 1г/день. Биологические эффекты растительных полифенолов разнообразны и специфичны, что обусловлено разнообразием их химического строения. В исследованиях показано, что диеты, богатые фруктами и овощами, снижают риск развития ряда хронических заболеваний, связанных с системным малоактив- ным хроническим воспалением, таких как диабет 2-го типа, атеросклероз и рак; высокий уровень потребления фруктов и овощей обратно пропорционален заболеваемости рядом дегенеративных заболеваний, подтверждены антиоксидантные, противовоспалитель-ные, иммуномодулирующие, антигипертензивные, нейропротекторные, гепатопротекторные эффекты растительных полифенолов, показана польза при реабилитации и профилактике сердечно-сосудистых и нейроваскулярных заболеваний.
DAPTMGY (DTY) is an oligopeptide derived from marine microalgae with proven potential to combat oxidative stress in previous research. The composition, ordering, and active sites of amino acids play a key role in activity studies and are also the research trends in recent years. As an oligopeptide with a molecular weight of less than 1000 Da, DTY is of great significance to explore the active site and structure-activity relationship. This study used quantum mechanics to optimize DTY’s structure and predict the active site through molecular orbits, energy, and charge. In addition, an LPS-treated HUVEC cell was established as an oxidative-stress model. DTY could reduce mitochondrial oxidative stress and inhibit ROS production by enhancing the antioxidant enzymes SOD, GPX, and HO-1. Moreover, it was confirmed to inhibit inflammation and apoptosis through the NF-κB and MAPK signaling pathways. Lastly, the correlation of the oligopeptide DTY’s active site and antioxidative-stress activity was verified by molecular docking, showing that hydrogen bonding is the main force, which was also the main factor for antioxidant activity.
On the surface of tea infusions, the formation of a transparent, shiny film which cracks upon disturbance can often be observed. This study aims to determine how water composition, tea varieties, and tea additives impact the formation and properties of tea film, often also called tea scum. The strength of the surface film, composed of polyphenols complexed with various ions from tap water, was investigated by interfacial rheology. Microscopy and ellipsometry were used to investigate structure and thickness of the adsorption layer, respectively. We find that green tea forms more visible layers than black tea in soft and moderate artificial tap water, but in these same waters, black tea demonstrated greater surface strength. In hard artificial tap water, green tea demonstrated greater surface strength than black. No visible layer nor surface strengthening was observed on rooibos tea. Brews in hard artificial tap water formed brittle films for green tea, fracturing at strains one order of magnitude lower than in soft or moderate. Despite large variations in film strength, black tea at all water hardness levels tested formed a film with 20 nm thickness. In black tea an increased resilience to deformation was found when adding β-casein, a protein found in milk.
Phytonutrients and Neurological Disorders: Therapeutic and Toxicological Aspects provides and assesses the latest research and developments surrounding the use of phytonutrients for the treatment of neurological disorders. The volume analyzes advances in phytonutrient isolation, characterization and therapeutic applications, giving particular emphasis to mechanisms and safety profiles. The book takes toxicological considerations into account, including adverse drug reactions, toxicokinetics and toxicodynamics. Sections cover bioactive compound classes and biosynthesis pathways, general considerations, including quality control, standardization, and technology, and toxicology. This title is a comprehensive work on the latest research in phytonutrients and neurological disorders that will be useful to researchers and medical practitioners.
Purpose: Green tea is known as a potent anti-oxidant, anti-carcinogen, and genetic protector. Glyphosate (N-phosphonomethyl glycine) is a widely used non-selective herbicide that causes DNA damage. The present study was conducted to investigate the protective effects of green tea in human blood lymphocytes exposed to glyphosate using the Sister Chromatid Exchange (SCE) frequency method. Methods: Peripheral blood was obtained from 10 volunteers and cultured through four different conditions. Four groups were divided into control, glyphosate only (300 ng/mL), glyphosate and low ($20{mu}m$) concentrations of epigallocatechin gallate (EGCG) and glyphosate and high ($100{mu}m$) concentrations of EGCG. Results: The glyphosate exposed groups had a higher mean SCE frequency ($10.33{pm}2.50$) than the control group ($6.38{pm}2.28$, p<0.001). The low concentrations of EGCG groups had a lower mean SCE frequency ($9.91{pm}1.93$) than the glyphosate-only group, although this difference was not significant (p=0.219). However, the high concentration group ($9.49{pm}1.85$) had a significantly lower SCE frequency than the glyphosate-only group (p=0.001). Conclusion: EGCG has a gene protective effect in human lymphocytes exposed to the genotoxicity of glyphosate in the case of high concentrations.
Gastrointestinal cancer is one of the most prevalent causes of cancer-related deaths in the world. Recent research demonstrates that phytochemicals are critical in preventing and managing gastrointestinal cancer. The increased intake of phytochemicals could reduce the risk of cancer by inhibiting cancer cell proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis as well as cancer cell metastasis. These mechanisms are also known to counter Helicobacter pylori infection and modulate gut microbiota. There is preliminary data suggesting that daily supplementation with high doses of certain vitamins combined with conventional therapeutic agents may enhance their growth inhibitory effects on tumor cells and protect normal tissues against some of their toxic effects. This book attempts to fill gaps on the role of phytonutrients in the treatment of cancer in the gastrointestinal tract (GIT). It discusses the action of individual vitamins on cellular and molecular parameters and describes how vitamins inhibit protein kinase C activity, increase the production of certain growth factors, and modulate the expression of a number of oncogenes. The book is divided into 2 parts. The first part summarizes the pathophysiology of GIT cancers and introduces readers to anticancer phytonutrients. A chapter on the status of FDA approved nutraceuticals rounds up this section. The second part of the book provides a systematic review on the different plant derived chemicals that can be used to treat GIT cancer. Each chapter in this section focuses on a specific type of phytochemical agent and its molecular mechanisms relevant to the disease. This book will give the reader a holistic view of gastrointestinal cancer treatment and the value of natural compounds in developing functional food and drugs for preventive medicine.
Purpose
A bulk of observational studies have revealed the protective role of green tea supplementation in cardiovascular diseases. The current systematic review and meta-analysis study aimed to establish the effects of green tea supplementation on cardiovascular risk factors including lipid profile, blood pressure, glycemic control markers and CRP.
Methods
A systematic literature search of randomized clinical trials (RCTs) that investigated the effects of green tea supplementation and cardiovascular risk factors was undertaken in online databases including PubMed/Medline, Scopus, Web of Science, and Embase using a combination of green tea and cardiovascular risk factors search terms. Meta-analyses were carried out using a random-effects model. The I² index was used to assess the heterogeneity of RCTs.
Results
Among the initial 11,286 studies that were identified from electronic databases search, 55 eligible RCTs with 63 effect sizes were eligible. Results from the random effects meta-analysis showed that GTE supplementation significantly reduced TC (WMD = −7.62; 95% CI: −10.51, −4.73; P = < 0.001), LDL-C (WMD = −5.80; 95% CI: −8.30, −3.30; P = < 0.001), FBS (WMD = −1.67; 95% CI: −2.58, −0.75; P = < 0.001), HbA1c (WMD = −0.15; 95% CI: −0.26, −0.04; P = 0.008), DBP (WMD = −0.87; 95% CI: −1.45, −0.29; P = 0.003), while increasing HDL-C (WMD = 1.85; 95% CI: 0.87, 2.84; P = 0.010). Subgroup analyses based on the duration of supplementation (≥ 12 vs. < 12 weeks), dose of green tea extract (GTE) (≥1,000 vs. < 1,000 mg/d), sex (male, female, and both), baseline serum levels of lipid profile, and glycemic control factors demonstrated different results for some risk factors.
Conclusion
The current study suggests improvements in the lipid and glycemic profiles following green tea supplementation. These findings support previous evidence showing the health benefits of green tea supplementation on cardiometabolic risk factors.
Previous reports revealed that peel extracts of Ficus carica (fig) have a wide range of pharmacological and biological activities. The current study aimed to determine the phytochemical components of the ethanol extracts of Peggy Red fig (PRF) and Green fig (GF) peels by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, along with its antioxidant properties and neuroprotective effect in Caenorhabditis elegans. LC-MS/MS analysis confirmed 50 compounds in the extract, which revealed the presence of phenols, flavonoids, and anthocyanins, and exhibited in vitro antioxidant activity. PRF and GF peel had 163.25 (mg gallic acid equivalent [mg GAE]) g-1, 125.32 (mg GAE) g-1 of total phenolic content, 62.52 (mg rutin equivalent [mg RE]) g-1, and 43.36 (mg RE) g-1 flavonoids content, respectively. In all antioxidant assays, the extract of PRF peel showed higher antioxidant activity than the GF peel, and the extract of PRF peel could effectively reduce the aggregation of amyloid-beta (Aβ), decrease the paralysis of the body, and increase the antioxidant enzyme activities to reduce the toxicity of Aβ1-42 in Alzheimer's disease (AD) transgenic C. elegans CL4176. Therefore, PRF peel extract may have potential applications as a new source for drug development against AD.
Background
This study was conducted to examine the impacts of coffee and green tea consumption on cardiovascular disease (CVD) mortality among people with severe hypertension.
Methods and Results
In the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk), 18 609 participants (6574 men and 12 035 women) aged 40 to 79 years at baseline who completed a lifestyle, diet, and medical history questionnaire, and health examinations, were followed up until 2009. We classified the participants into four blood pressure (BP) categories: optimal and normal BP, high‐normal BP, grade 1 hypertension, and grade 2–3 hypertension. A Cox proportional hazard model was used to calculate the multivariable hazard ratios with 95% CIs of CVD mortality. During the 18.9 years of median follow‐up, a total of 842 CVD deaths were documented. Coffee consumption was associated with an increased risk of CVD mortality among people with grade 2–3 hypertension; the multivariable hazard ratios (95% CI) of CVD mortality were 0.98 (0.67–1.43) for <1 cup/day, 0.74 (0.37–1.46) for 1 cup/day, and 2.05 (1.17–3.59) for ≥2 cups/day, compared with non–coffee drinkers. Such associations were not found among people with optimal and normal, high‐normal BP, and grade 1 hypertension. Green tea consumption was not associated with an increased risk of CVD across any BP categories.
Conclusions
Heavy coffee consumption was associated with an increased risk of CVD mortality among people with severe hypertension, but not people without hypertension and with grade 1 hypertension. In contrast, green tea consumption was not associated with an increased risk of CVD mortality across all categories of BP.
In this chapter, the traditional use, the phytochemical composition, and the pharmacological activities of African medicinal plants displaying antibacterial effects were reported. We have pooled together the plants and phytochemicals active in pathogens of the family Enterobacteriaceae, as well as Pseudomonas aeruginosa, Gram-positive bacteria, and Mycobacteria. We also identified potent antibacterial medicinal plants of Africa having other pharmacological activities such as anti-inflammatory, anticancer, anti-diabetic, central nervous system, cardiovascular, anti-parasitic, hepatoprotective, immunomodulatory, nephroprotective, reproduction and digestive systems, antiviral, and wound healing activities. The documented plants can be further investigated globally by scientists to develop new herbal drugs to combat various types of bacterial infections.
Natural antioxidants exhibit a wide range of biological effects including antibacterial, antiviral, anti‐inflammatory, antiallergenic, antithrombotic, and vasodilatory actions. Medicinal plants basically contain various antioxidants, e.g., vitamins, carotenoids, and phenolic compounds such as catechin, epicatechin, lignin and tannins, and anthocyanins. In the group of polyphenolic compounds and flavonoids have been extensively studied and include catechins, proanthocyanins, anthocyanidins, flavones, flavonols, and their glycosides, which represent some major groups of natural antioxidants having significant protective effects against various human diseases.
The effects of dietary tea catechins on the levels of alpha-tocopherol and lipid peroxidation in both plasma and erythrocytes, as well as their effects on erythrocyte deformability, were examined in rats fed on high palm and perilla oil diets. The decrease in alpha-tocopherol concentration and the increase in lipid peroxidation level were much more pronounced in the perilla oil group than in the palm oil group. The addition of tea catechins to these diets significantly prevented the alpha-tocopherol concentration from decreasing. These results suggest that tea catechins may counteract a decrease in alpha-tocopherol by acting as an antioxidant in vivo. Furthermore, the lipid peroxidation in the plasma of rats fed perilla oil was slightly but significantly reduced by the supplemented tea catechins. However, no measurable differences were observed in the deformability of the erythrocytes in any of the groups. It is therefore likely that the erythrocytes are not severely enough affected by the lipid peroxidation to influence their deformability.
Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of tea flavonoids in the prevention of atherosclerosis, we investigated the effects of tea flavonoids on the susceptibility of low-density lipoprotein (LDL) to oxidative modification. In an in vitro study, catechins or theaflavins (25-400 mumol/L) were added to plasma and incubated for 3 h at 37 degrees C. Then, the LDL fraction was separated by ultracentrifugation. The oxidizability of LDL was estimated by measuring conjugated diene, thiobarbituric acid-reactive substances (TBARS), and lipid peroxides after cupric sulfate was added. TBARS and lipid peroxides in the supernates were also measured after incubation with macrophages. Catechins significantly (P < 0.01 by ANOVA) and dose-dependently prolonged the lag time before initiation of oxidation. Among the catechins, epigallocatechin gallate exerted the most marked effect, prolonging the oxidation lag time more than vitamin E at the same molar concentration. Theaflavins exerted stronger inhibitory effects than catechins. Macrophage-mediated LDL oxidation was also inhibited by adding these tea flavonoids to the plasma samples. In an in vivo study, 14 healthy volunteers consumed 750 mL black tea/d for 4 wk. After the subjects had consumed tea for 4 wk, the lag time before LDL oxidation was significantly (P < 0.01) prolonged from 54 to 62 min. This minor prolongation occurred despite much lower plasma flavonoids than were used in vitro. No significant change was observed in eight control volunteers. LDL exposed to tea flavonoids in vitro or in vivo reduced oxidizability. We speculate that tea flavonoids may have a role in ameliorating atherosclerosis.
The flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties in vitro. The interactions of four structurally related flavonoids (quercetin, kaempferol, rutin and luteolin) with Cu2+ ions were investigated in terms of the extent to which they undergo complex formation through chelation or modification through oxidation, as well as in their structural dependence. The ortho 3',4'-dihydroxy substitution in the B ring is shown to be important for Cu2+-chelate formation, thereby influencing the antioxidant activity. The presence of a 3-hydroxy group in the flavonoid structure enhances the oxidation of quercetin and kaempferol, whereas luteolin and rutin, each lacking the 3-hydroxy group, do not oxidize as readily in the presence of Cu2+ ions. The results also demonstrate that the reactivities of the flavonoids in protecting low-density lipoprotein (LDL) against Cu2+ ion-induced oxidation are dependent on their structural properties in terms of the response of the particular flavonoid to Cu2+ ions, whether chelation or oxidation, their partitioning abilities between the aqueous compartment and the lipophilic environment within the LDL particle, and their hydrogen-donating antioxidant properties.
Some epidemiological studies have associated tea drinking with several health benefits, while other such studies have been inconclusive. The liver enzyme, xanthine oxidase (XO) produces uric acid and reactive oxygen species (ROS) during the catabolism of purines. Excess of the former can lead to gout and of the latter to increased oxidative stress, mutagenesis and possibly cancer. Polyphenols are antioxidants, and it has been suggested that they can reduce oxidative stress by their antioxidant properties. We report here on the inhibition of XO by five tea catechins and two flavones. The Ki values (microM) and types of inhibition were catechin (C) (Ki = 303.95, uncompetitive), epicatechin (EC) (Ki = 20.48, mixed), epigallocatechin (EGC) (Ki = 10.66, mixed), epicatechin gallate (ECg) (Ki = 2.86, mixed) and epigallocatechin gallate (EGCg) (Ki = 0.76, competitive). The Ki of EGCg was similar to that of allopurinol (Ki = 0.30, mixed), the drug of choice for inhibition of XO in gout patients. Thus, tea catechins may act at.an earlier stage than has previously been suspected, by inhibiting ROS production, rather than only neutralizing the already formed ROS. This suggests a new mechanism whereby tea drinking may prevent oxidative stress related diseases, e.g. atherosclerosis and cancer.
The inhibitory activity of tea against tumorigenesis has been demonstrated in many animal models and has been suggested by some epidemiological studies. Such activity has generally been attributed to tea catechins. To understand the bioavailability of tea catechins in humans, we gave 18 individuals different amounts of green tea and measured the time-dependent plasma concentrations and urinary excretion of tea catechins. After taking 1.5, 3.0, and 4.5 g of decaffeinated green tea solids (dissolved in 500 ml of water), the maximum plasma concentration (Cmax) of (-)-epigallocatechin-3-gallate (EGCG) was 326 ng/ml, the Cmax of (-)-epigallocatechin (EGC) was 550 ng/ml, and the Cmax of (-)-epicatechin (EC) was 190 ng/ml. These Cmax values were observed at 1.4-2.4 h after ingestion of the tea preparation. When the dosage was increased from 1.5 to 3.0 g, the Cmax values increased 2.7-3.4-fold, but increasing the dose to 4.5 g did not increase the Cmax values significantly, which suggested a saturation phenomenon. The half-life of EGCG (5.0-5.5 h) seemed to be higher than the half-life of EGC or EC (2.5-3.4 h). EGC and EC, but not EGCG, were excreted in the urine. Over 90% of the total urinary EGC and EC was excreted within 8 h. When the tea dosage was increased, the amount of EGC and EC excretion seemed to increase, but a clear dose-response relationship was not observed. The present study provides basic pharmacokinetic parameters of green tea catechins in humans; these parameters may be used to estimate the levels of these compounds after drinking tea.
The inhibitory effects of five tea polyphenols, namely theaflavin (TF1), theaflavin-3-gallate (TF2), theaflavin-3,3'-digallate (TF3), (-)-epigallocatechin-3-gallate (EGCG), and gallic acid, and propyl gallate (PG) on xanthine oxidase (XO) were investigated. These six antioxidant compounds reduce oxidative stress. Theaflavins and EGCG inhibit XO to produce uric acid and also act as scanvengers of superoxide. TF3 acts as a competitive inhibitor and is the most potent inhibitor of XO among these compounds. Tea polyphenols and PG all have potent inhibitory effects (>50%) on PMA-stimulated superoxide production at 20 similar to 50 mu M in HL-60 cells. Gallic acid (GA) showed no inhibition under the same conditions. At 10 mu M, only EGCG, TF3, and PG showed significant inhibition with potency of PG > EGCG > TF3. The superoxide scavenging abilities of these six compunds are as follows: EGCG > TF2 > TF1 > GA > TF3 > PG. PG was the most potent inhibitor of PMA-stimulated H2O2 production in HL-60 cells. The order of H2O2 scavenging ability was TF2 > TF3 > TF1, EGCG > PG, GA. Therefore, the antioxidative activity of tea polyphenols and PG is due not only to their ability to scavenge superoxides but also to their ability to block XO and related oxidative signal transducers.
Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical tumor promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin -1 alpha (IL-1α) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theafla-vine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1αa mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against tumorigenesis. The results of this study suggest that black tea, specifically polyphenols present therein, may be useful against cutaneous inflammatory responses in human population.
There is currently much interest in phytochemicals as bioactive components of food. The roles of fruit, vegetables and red wine in disease prevention have been attributed, in part, to the antioxidant properties of their constituent polyphenols (vitamins E and C, and the carotenoids). Recent studies have shown that many dietary polyphenolic constituents derived from plants are more effective antioxidants in vitro than vitamins E or C, and thus might contribute significantly to the protective effects in vivo. It is now possible to establish the antioxidant activities of plant-derived flavonoids in the aqueous and lipophilic phases, and to assess the extent to which the total antioxidant potentials of wine and tea can be accounted for by the activities of individual polyphenols.
Oxidative modification of low-density lipoproteins(LDL) may play an important role in the development of atherosclerosis. alpha-Tocopherol functions as a major antioxidant in human LDL. The present study was to test whether green tea catechins (GTC) would protect or regenerate alpha-tocopherol in human LDL. The oxidation of LDL incubated in sodium phosphate buffer (pH 7.4, 10 mM) was initiated by addition of 1.0 mM of 2,2'-azobis(2-amidinopropane) dihydrochloride at 40 degrees C. It was found that alpha-tocopherol was completely depleted within 1 h. Under the same experimental conditions, the longjing GTC extracts demonstrated a dose-dependent protective activity to alpha-tocopherol in LDL at concentrations ranging from 2 to 20 mu M. Four pure epicatechin derivatives showed varying protective activity against depletion of alpha-tocopherol in LDL with (-)-epigalloeatechin (EGC) and (-)-epigallocatechin gallate (EGCG) being less effective than (-)-epicatechin (EC) and (-)-epicatechin gallate (ECG). The results showed that addition of longjing GTC extracts, EC, EGG, and EGCG at 5, 10, and 15 min to the incubation mixture demonstrated a gradual regeneration of alpha-tocopherol in human LDL.
Tea is a popular beverage consumed worldwide. The metabolic fate of its major constituents, catechins, however, is not well-known. In this study, two catechin metabolites were detected in the urine and plasma of human volunteers after ingestion of green tea. These metabolites were identified by LC/ESI-MS and NMR as (−)-5-(3‘,4‘,5‘-trihydroxyphenyl)-γ-valerolactone (M4) and (−)-5-(3‘,4‘-dihydroxyphenyl)-γ-valerolactone (M6). The renal excretion of M4 and M6 had a 3 h lag time and peaked 7.5−13.5 h after ingestion of a single dose of green tea, while (−)-epigallocatechin (EGC) and (−)-epicatechin peaked at 2 h. M4 and M6 were two major tea metabolites with urinary cumulative excretions as high as 8−25 times the levels of EGC and (−)-epicatechin in some of our subjects, and accounted for 6−39% of the amounts of ingested EGC and (−)-epicatechin. Both the metabolites appeared to be produced by intestinal microorganisms, with EGC and (−)-epicatechin as the precursors of M4 and M6, respectively. Repeated ingestion of green tea produced a slight accumulative effect of the metabolites. They were also detected in the plasma, exhibiting kinetics similar to those of the urinary metabolites, and in the feces. Study on these metabolites may help us further understand the cancer chemopreventive actions and other beneficial effects of tea.
In this animal study, Wistar rats were fed 2.5% green tea (longjing) leaves, for 27 and 63 weeks; the changes of GOT, GPT, γ-GT, and creatinine were not significant in the treated group as compared with the control. These results suggested that long-term feeding of green tea leaves was not toxic to the liver or kidney. Serum total cholesterol, triglyceride, and LDL-C were decreased in the tested group. Interestingly, the dietary intakes of the two groups were approximately the same, but the body weights of the tea-fed group were decreased 10−18% compared with those of the control. The activities of antioxidant enzymes (SOD and catalase) and phase II enzyme (GST) and glutathione concentration in the liver of Wistar rats were significantly higher in the treated group. The biological significance of these results can be implicated in relation to the hypolipidemic effect as well as the cancer chemopreventive action of green tea. Keywords: Longjing tea; GST; HDL-C; hypolipidemic; LDL-C; phase II enzyme; SOD
Spectral, acid−base, and redox properties of theaflavin radicals were studied by pulse radiolysis in aqueous solutions. Theaflavin radicals are generated by the azide radical one-electron oxidation of theaflavin, theflavin gallates A and B, and theaflavin digallate. Being relatively strong transient oxidant, N3• oxidizes more than one phenolic site in the complex polyphenols. The resulting mixture of phenoxyl radicals transforms via an intramolecular electron transfer to the hydroxycycloheptenone radical, with apparently lowest reduction potential. The neutral hydroxycycloheptenone radical is more aromatic than the parent compound, which reflects in high rate constant of the formation of the radical. The rate of the reaction of theaflavin with the superoxide radical at pH 7, k = 1 × 107 M-1 s-1, is an order of magnitude higher than that with epigallocatechin gallate (EGCG), k = 7.3 × 105 M-1 s-1, in spite of higher reduction potential of the theaflavin radicals (E7 = 0.53 V vs E7 = 0.44 V for EGCG). Even the substitution in the adjacent benzene ring has relatively small effect on the electron density in the radical. Purpurogallin radical, with three hydroxy groups on the benzene ring, has pKr1 = 4.7 and E7 = 0.48 V, as compared to the theaflavin radical, with only two hydroxy groups on benzene, having pKr = 4.3 and E7 = 0.51 V. The electron donating ability of theaflavins, which are major antioxidants in black tea, is quantitatively assessed on the basis of physicochemical characteristics of daughter radicals and their potential biological action discussed.
Nitric oxide (NO) plays an important role in inflammation and also in multiple stages of carcinogenesis. We investigated the effects of various tea polyphenols, including theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3′-gallate, theaflavin-3,3′-digallate, thearubigin, and (−)-epigallocatechin-3-gallate on the induction of NO synthase in lipopolysaccharide-activated murine macrophages, RAW 264.7 cells. Theaflavin-3,3′-digallate was found to be stronger than (−)-epigallocatechin-3-gallate in inhibiting NO generation and inducible NO synthase protein in activated macrophages, while theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3′-gallate and thearubigin were less effective. Inhibition of NO production was observed when cells were cotreated with theaflavin-3,3′-digallate and lipopolysaccharide. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses demonstrated that significantly reduced 130-kDa protein and mRNA levels of inducible NO synthase were expressed in lipopolysacchride-activated macrophages with theaflavin-3,3′-digallate, compared to those without theaflavin-3,3′-digallate. Electrophoretic mobility shift assay (EMSA) indicated that theaflavin-3,3′-digallate blocked the activation of nuclear factor κB (NF-κB), a transcription factor necessary for inducible NO synthase induction. Theaflavin-3,3′-digallate also blocked phosphorylation of IκB from cytosolic fraction and reduced lipopolysacchride-induced nuclear accumulation of transcription factor NF-κB p65 and p50 subunits. These results suggest that theaflavin-3,3′-digallate decreases the protein levels of inducible NO synthase by reducing the expression of inducible NO synthase mRNA, and the reduction could be via preventing the activation of NF-κB, thereby inhibiting the induction of inducible NO synthase transcription. It was also demonstrated that the gallic acid moiety of theaflavin-3,3′-digallate is essential for their potent anti-inflammation activity.
The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 μg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from black tea inhibited LOX-dependent activity by 30–75%. The formation of 5-, 12-, and 15-LOX metabolites was inhibited to a similar extent. Tea polyphenols also inhibited COX-dependent arachidonic acid metabolism in microsomes from normal colon mucosa, with ECG showing the strongest inhibition. The formation of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was decreased to a greater extent than other metabolites. The inhibitory effects of tea polyphenols on COX activity, however, were less pronounced in tumor microsomes than in normal colon mucosal microsomes. Theaflavins strongly inhibited the formation of TBX and HHT, but increased the production of prostaglandin E2 (PGE2) in tumor microsomes. The enhancing effect of theaflavins on PGE2 production was related to the COX-2 level in the microsomes. Although theaflavin inhibited ovine COX-2, its activity in the formation of PGE2 was stimulated by theaflavin when ovine COX-2 was mixed with microsomes, suggesting that theaflavin affects the interaction of COX-2 with other microsomal factors (e.g. PGE synthase). The present results indicate that tea polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in humans.
Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582-3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1-24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy-eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30-46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects.
Tea is grown in about 30 countries but is consumed worldwide, although at greatly varying levels. It is the most widely consumed beverage aside from water with a per capita worldwide consumption of approximately 0.12 liter per year. Tea is manufactured in three basic forms. Green tea is prepared in such a way as to preclude the oxidation of green leaf polyphenols. During black tea production oxidation is promoted so that most of these substances are oxidized. Oolong tea is a partially oxidized product. Of the approximately 2.5 million metric tons of dried tea manufactured, only 20% is green tea and less than 2% is oolong tea. Green tea is consumed primarily in China, Japan, and a few countries in North Africa and the Middle East. Fresh tea leaf is unusually rich in the flavanol group of polyphenols known as catechins which may constitute up to 30% of the dry leaf weight. Other polyphenols include flavanols and their glycosides, and depsides such as chlorogenic acid, coumarylquinic acid, and one unique to tea, theogallin (3-galloylquinic acid). Caffeine is present at an average level of 3% along with very small amounts of the other common methylxanthines, theobromine and theophylline. The amino acid theanine (5-N-ethylglutamine) is also unique to tea. Tea accumulates aluminum and manganese. In addition to the normal complement of plant cell enzymes, tea leaf contains an active polyphenol oxidase which catalyzes the aerobic oxidation of the catechins when the leaf cell structure is disrupted during black tea manufacture. The various quinones produced by the enzymatic oxidations undergo condensation reactions which result in a series of compounds, including bisflavanols, theaflavins, epitheaflavic acids, and thearubigens, which impart the characteristic taste and color properties of black tea. Most of these compounds readily form complexes with caffeine. There is no tannic acid in tea. Thearubigens constitute the largest mass of the extractable matter in black tea but their composition is not well known. Proanthocyanidins make up part of the complex. Tea peroxidase may be involved in their generation. The catechin quinones also initiate the formation of many of the hundreds of volatile compounds found in the black tea aroma fraction. Green tea composition is very similar to that of the fresh leaf except for a few enzymatically catalyzed changes which occur extremely rapidly following plucking. New volatile substances are produced during the drying stage. Oolong tea is intermediate in composition between green and black teas.
Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.
In this study we examined the effects of green tea and its major components, (-)-epigallocatechin gallate (EGCG) and caffeine, on the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. We also studied the effects of green tea and EGCG on O6-methylguanine and 8-hydroxydeoxyguanosine (8-OH-dGuo) formation in lung tissues caused by NNK treatment. Mice were given 2% tea, 560 ppm EGCG, or 1120 ppm caffeine in drinking water for 13 weeks. During this time, NNK (11.65 mg/kg body weight) was administered by gavage three times weekly for 10 weeks from weeks 3 to 12. The bioassay was terminated 6 weeks after the last NNK treatment. Mice treated with NNK developed 22.5 lung adenomas per mouse, whereas NNK-treated mice that drank green tea or EGCG as drinking water developed only 12.2 (P less than 0.01) and 16.1 (P less than 0.05) tumors per mouse, respectively. Mice that drank green tea or caffeine solution showed lower body weight gains, although little difference in water and diet consumption was noted in these groups. While green tea and EGCG exerted little effect on the formation of O6-methylguanine, a critical DNA lesion in NNK lung tumorigenesis, both treatments suppressed the increase of 8-OH-dGuo levels in mouse lung DNA. The inhibition of 8-OH-dGuo formation in lung DNA by green tea and EGCG is consistent with their ability to inhibit lung tumorigenesis by NNK. Because 8-OH-dGuo is a DNA lesion caused by oxidative damage, these results suggest that the mechanism of inhibition by green tea and EGCG in NNK-induced lung tumorigenesis is due at least partly to their antioxidant properties.
This study examined the preventive effects of green tea extract on hyperlipidemia and lipid accumulation in the liver and aorta of mice fed an atherogenic diet enriched with 1.5% cholesterol, 0.5% cholic acid and 5% linoleic acid for a period of 14 weeks. The animals were given green tea extract in drinking water at doses of 50, 100 and 200 mg/kg/day. Treatment with green tea extract prevented the increase of serum cholesterol induced by the atherogenic diet 6 weeks after the start of the experiment. The increase of serum lipid peroxides was markedly prevented in a dose-related manner. The green tea extract also tended to prevent the increase of serum phospholipid and the decline of lecithin: cholesterol acyltransferase, but could not prevent decreases in serum triglycerides and high-density lipoprotein cholesterol. As for liver cholesterol, its content, particularly free cholesterol, in mice fed the atherogenic diet could be prevented from increasing by treatment with the extract at 50 and 100 mg/kg/day. In addition, the increase of aortic cholesterol, particularly esterified cholesterol, could be prevented in a dose-related manner. These results suggest that green tea has anti-atherosclerotic activity.
Increasing appreciation of the causative role of oxidative injury in many disease states places great importance on the reliable assessment of lipid peroxidation. Malondialdehyde (MDA) is one of several low-molecular-weight end products formed via the decomposition of certain primary and secondary lipid peroxidation products. At low pH and elevated temperature, MDA readily participates in nucleophilic addition reaction with 2-thiobarbituric acid (TBA), generating a red, fluorescent 1:2 MDA:TBA adduct. These facts, along with the availability of facile and sensitive methods to quantify MDA (as the free aldehyde or its TBA derivative), have led to the routine use of MDA determination and, particularly, the "TBA test" to detect and quantify lipid peroxidation in a wide array of sample types. However, MDA itself participates in reactions with molecules other than TBA and is a catabolic substrate. Only certain lipid peroxidation products generate MDA (invariably with low yields), and MDA is neither the sole end product of fatty peroxide formation and decomposition nor a substance generated exclusively through lipid peroxidation. Many factors (e.g., stimulus for and conditions of peroxidation) modulate MDA formation from lipid. Additional factors (e.g., TBA-test reagents and constituents) have profound effects on test response to fatty peroxide-derived MDA. The TBA test is intrinsically nonspecific for MDA; nonlipid-related materials as well as fatty peroxide-derived decomposition products other than MDA are TBA positive. These and other considerations from the extensive literature on MDA. TBA reactivity, and oxidative lipid degradation support the conclusion that MDA determination and the TBA test can offer, at best, a narrow and somewhat empirical window on the complex process of lipid peroxidation. The MDA content and/or TBA reactivity of a system provides no information on the precise structures of the "MDA precursor(s)," their molecular origins, or the amount of each formed. Consequently, neither MDA determination nor TBA-test response can generally be regarded as a diagnostic index of the occurrence/extent of lipid peroxidation, fatty hydroperoxide formation, or oxidative injury to tissue lipid without independent chemical evidence of the analyte being measured and its source. In some cases, MDA/TBA reactivity is an indicator of lipid peroxidation; in other situations, no qualitative or quantitative relationship exists among sample MDA content, TBA reactivity, and fatty peroxide tone. Utilization of MDA analysis and/or the TBA test and interpretation of sample MDA content and TBA test response in studies of lipid peroxidation require caution, discretion, and (especially in biological systems) correlative data from other indices of fatty peroxide formation and decomposition.
We have evaluated the abilities of ferulic acid, (+/-) catechin, (+) catechin and (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH.), hypochlorous acid (HOCl) and peroxyl radicals (RO2.). Ferulic acid tested at concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes. Both (+/-) and (+) catechin and (-) epicatechin were much more effective. All the compounds tested reacted with trichloromethyl peroxyl radical (CCl3 O2.) with rate constants > 1 x 10(6) M-1 s-1. A mixture of FeCl3-EDTA, hydrogen peroxide (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl radicals (OH.) which are detected by their ability to cause damage to the sugar deoxyribose. Ferulic acid, (+) and (+/-) catechin and (-) epicatechin inhibited deoxyribose damage by reacting with OH. with rate constants of 4.5 x 10(9)M-1 s-1, 3.65 x 10(9) M-1 s-1, 2.36 x 10(9) M-1 s-1 and 2.84 x 10(9) M-1 s-1 respectively. (-) Epicatechin, ferulic acid and the (+) and (+/-) catechins exerted pro-oxidant action, accelerating damage to DNA in the presence of a bleomycin-iron complex. On a molar basis, ferulic acid was less effective in causing damage to DNA compared with the catechins. A mixture of hypoxanthine and xanthine oxidase generates O2-. which reduces cytochrome c to ferrocytochrome c. (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a concentration dependent manner. Ferulic acid and (+/-) catechin had only weak effects. All the compounds tested were able to scavenge hypochlorous acid at a rate sufficient to protect alpha-1-antiproteinase against inactivation. Our results show that catechins and ferulic acid possess antioxidant properties. This may become important given the current search for "natural" replacements for synthetic antioxidant food additives.
Male rats were given 2% green tea as their drinking water for 2 wk before a single ip injection of the carcinogen 2-nitropropane (2NP) (100 mg/kg body weight) and liver nuclear 8-hydroxydeoxyguanosine (8-OHdG) levels and hepatotoxicity parameters were determined 6 or 15 hr thereafter. The increase of 8-OHdG adducts in liver nuclear DNA caused by 2NP was depressed 50% at both time points with the green tea pretreatment. The time-dependent elevations of serum aminotransferases and lactate dehydrogenase values by 2NP were also effectively prevented. However, green tea had no obvious effects on the falls in serum lipid peroxide and triglyceride levels associated with carcinogen exposure. Increases of hepatic lipid peroxide levels with 2NP were depressed 100 and 30%, at 6 and 15 hr, respectively, by green tea and the decrease in hepatic glycogen content at 6 hr was clearly alleviated. Histopathological examination revealed effective protection against induction of hepatic degenerative changes by 2NP at 15 hr. Drinking crude catechin extract solution with the same concentration of (-)epigallocatechin gallate as green tea provided protection at 6 hr, but with only half the effectiveness. These findings demonstrate that green tea can effectively block oxidative DNA damage to the liver as well as hepatotoxicity in rats treated with 2NP.
8-Hydroxydeoxyguanosine (8-OH-dG) was determined as a marker of oxidative DNA damage in male B6C3F1 mice treated with the hepatocarcinogen pentachlorophenol (PCP). A single oral administration of PCP (0-80 mg/kg) significantly and dose-dependently increased the 8-OH-dG level specifically in the liver at 6 hr. Repeated doses (0-80 mg/kg) over 5 days caused a further increase. Elevation of the 8-OH-dG level caused by a single dose of PCP (60 mg/kg) was not affected by ip injection of buthionine sulfoximine (2 mmol/kg), an inhibitor of GSH synthesis, or aminotriazole (1 g/kg), an inhibitor of catalase, showing no clear evidence for enhancement by the oxidative stress due to reduction of antioxidative factors under these experimental conditions. However, examination of the effects of natural antioxidants on repeated PCP treatment (60 mg/kg/day, for 5 days) revealed that oral administration of vitamin E and diallyl sulfide 3 hr before each PCP challenge significantly protected against elevation of hepatic 8-OH-dG levels. beta-Carotene did not have any effect. Ellagic acid, epigallocatechin gallate and vitamin C demonstrated partial protection. These findings indicate that PCP causes oxidative DNA damage in the target organ liver which can be blocked by a number of antioxidant agents.
In prior studies we and others have shown that oral feeding of a polyphenolic fraction isolated from green tea (GTP) or water extract of green tea affords protection against ultraviolet B (UVB) radiation-induced carcinogenesis in SKH-1 hairless mice (Wang et al., Carcinogenesis 12, 1527-1530, 1991). It is known that exposure of murine skin to UVB radiation results in cutaneous edema, depletion of the antioxidant-defense system and induction of ornithine decarboxylase (ODC) and cyclooxygenase activities. In this study we assessed the protective effect of GTP on these UVB radiation-caused changes in murine skin. Oral feeding of 0.2% GTP (wt/vol) as the sole source of drinking water for 30 days to SKH-1 hairless mice followed by irradiation with UVB (900 mJ/cm2) resulted in significant protection against UVB radiation-caused cutaneous edema (P < 0.0005) and depletion of the antioxidant-defense system in epidermis (P < 0.01-0.02). The oral feeding of GTP also resulted in significant protection against UVB radiation-caused induction of epidermal ODC (P < 0.005-0.01) and cyclooxygenase activities (P < 0.0001) in a time-dependent manner. Our data indicate that the inhibition of UVB radiation-caused changes in these markers of tumor promotion in murine skin by GTP may be one of the possible mechanisms of chemopreventive effects associated with green tea against UVB-induced tumorigenesis. The results of this study suggest that green tea, specifically polyphenols present therein, may be useful against inflammatory responses associated with the exposure of skin to solar radiation.
Free radicals vary widely in their thermodynamic properties, ranging from very oxidizing to very reducing. These thermodynamic properties can be used to predict a pecking order, or hierarchy, for free radical reactions. Using one-electron reduction potentials, the predicted pecking order is in agreement with experimentally observed free radical electron (hydrogen atom) transfer reactions. These potentials are also in agreement with experimental data that suggest that vitamin E, the primary lipid soluble small molecule antioxidant, and vitamin C, the terminal water soluble small molecule antioxidant, cooperate to protect lipids and lipid structures against peroxidation. Although vitamin E is located in membranes and vitamin C is located in aqueous phases, vitamin C is able to recycle vitamin E; i.e., vitamin C repairs the tocopheroxyl (chromanoxyl) radical of vitamin E, thereby permitting vitamin E to function again as a free radical chain-breaking antioxidant. This review discusses: (i) the thermodynamics of free radical reactions that are of interest to the health sciences; (ii) the fundamental thermodynamic and kinetic properties that are associated with chain-breaking antioxidants; (iii) the unique interfacial nature of the apparent reaction of the tocopherol free radical (vitamin E radical) and vitamin C; and (iv) presents a hierarchy, or pecking order, for free radical electron (hydrogen atom) transfer reactions.
Reactive oxygen species (ROS) have been implicated as being involved in tumor promotion processes. However, the mechanism
by which ROS modulate tumor promotion has not as yet been elucidated. In this report, we show that phorbol ester-type tumor
promoters (12-O-tetradecanoyl-phorbol-13-acetate [TPA], mezerein and 12-O-retinoylphor-bol-13-acetate [RPA]), which vary in their in vivo potencies, also differ in their effect on formation of hydrogen peroxide (H2O2) and oxidation of normal bases to 5-hydroxymethyl-2'-deoxyuridine [HMdU] and 8-hydroxyl-2'-deoxyguanosine [8-OHdG] in the
DNA of SENCAR mouse epidermis, though they are equipotent in causing infiltration of polymorpho-nuclear leukocytes (PMNs).
Treatment of SENCAR mice with the chemopreventive agents (-)-epigallocatechin gallate or tamoxifen (6.5 nmol) prior to application
of TPA (6.5 nmol) diminished PMN infiltration, and formation of H2O2, HMdU and 8-OHdG. These results strengthen the evidence that ROS are involved in tumor promotion, and that generation of
ROS and the subsequent oxidative DNA modification are related to the tumor-promoting potencies of the different phorbol ester-type
promoters.
Following subcutaneous injection of 1,2-dimethylhydrazine (DMH), which is carcinogenic to rat colon and liver, to Sprague-Dawley rats, a significant increase of 8-hydroxydeoxyguanosine (8-OHdG) was observed in the DNA of colonic mucosa and liver. The 8-OHdG formation reached the maximal level at about 24 h after the DMII injection. On the other hand, no increase of 8-OHdG was observed in the DNA of the kidney. Drinking green tea extract (GTE) for ten days prior to the DMH injection significantly inhibited the formation of 8-OHdG in the colon. These findings demonstrate that DMH causes oxidative damage to the DNA of its target organ, and that GTE protects colonic mucosa from this oxidative damage.
Evaluation of the vitro antioxidant activity of green and black tea, their in vivo effect on plasma antioxidant potential in man and the effect of milk addition.
The antioxidant activity of the tea, with and without milk, was tested in vitro by measuring the length of the peroxyl radical induced lag-phase. The in vivo activity was tested on two groups of five healthy adults. Each group ingested 300 ml of either black or green tea, after overnight fast. The experiment was repeated on a separate day, adding 100 ml whole milk to the tea (ratio 1:4 ). Five subjects acted as controls. The human plasma antioxidant capacity (TRAP) was measured before and 30, 50 and 80 min from the ingestion of tea.
Both teas inhibited the in vitro peroxidation in a dose-dependent manner. Green tea was sixfold more potent than black tea. The addition of milk to either tea did not appreciably modify their in vitro antioxidant potential. In vivo, the ingestion of tea produced a significant increase of TRAP (P <0.05), similar in both teas, which peaked at 30-50 min. When tea was consumed with milk, their in vivo activity was totally inhibited.
The paper shows that tea possesses a strong antioxidant activity in vitro which is believed to be exerted by its polyphenols moiety. It also provides compelling evidence that tea has also a potent in vivo activity in man. The promptness of the in vivo response suggests that the absorption of the bioactive components of tea takes place in the upper part of the gastrointestinal system. The inhibition of this effect by milk is thought to be due to the complexation of tea polyphenols by milk proteins. These findings might help to clarify the putative role of dietary poly- phenols in modulating oxidative stress in vivo.
Phosphatidylcholine hydroperoxide (PCOOH) measured using a chemiluminescence detector to examine colonic mucosal lipid hyperoxidation increased after injection of 1,2-dimethylhydrazine and green tea extract (GTE), which we previously showed inhibited carcinogenesis and oxidative DNA damage in the gastrointestinal tract. Therefore, the hyperoxidation of membrane phospholipids reflected well the degree of DNA damage and carcinogenic alteration, and may be a useful intermediate biomarker for initiation of carcinogenesis.
The recent explosion of interest in the bioactivity of the flavonoids of higher plants is due, at least in part, to the potential health benefits of these polyphenolic components of major dietary constituents. This review article discusses the biological properties of the flavonoids and focuses on the relationship between their antioxidant activity, as hydrogen donating free radical scavengers, and their chemical structures. This culminates in a proposed hierarchy of antioxidant activity in the aqueous phase. The cumulative findings concerning structure-antioxidant activity relationships in the lipophilic phase derive from studies on fatty acids, liposomes, and low-density lipoproteins; the factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.
Green tea polyphenols, major constituents of green tea, are potent chemopreventive agents in a number of experimental models of cancer in animals. The mechanisms of cancer protection by these agents are not clear, but may involve modulation of the enzyme systems responsible for the detoxification of chemical carcinogens. The present studies show that a green tea polyphenol extract (GTP) induces chloramphenicol acetyltransferase (CAT) activity in human heptoma HepG2 cells transfected with a plasmid construct which contains an antioxidant-responsive element (ARE) and a minimal glutathione S-transferase Ya promoter linked to the CAT reporter gene. This indicates that GTP stimulates the transcription of Phase II detoxifying enzymes through the ARE. To explore the upstream signaling pathways leading to gene expression, we studied the involvement of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 2 (ERK2) and c-Jun N-terminal kinase 1 (JNK1). Potent activation of ERK2 was seen following treatment of HepG2 cells with different concentrations of GTP. Similar to ERK2, JNK1 was also strongly activated by treatment with GTP, although to a lesser extent and in a different dose-dependent fashion. Kinetic studies revealed that GTP activation of JNK1 was delayed and sustained, whereas ERK2 activation was rapid and transient. Furthermore, GTP treatment also increased mRNA levels of the immediate-early genes c-jun and c-fos, as determined by reverse transcriptase-coupled polymerase chain reaction. Taken together, these studies provide insights into the action of GTP and suggest that the stimulation MAPKs may be the potential signaling pathways utilized by GTP to activate ARE-dependent genes.
Research was performed on the effect of tea, or tea and milk, instead of drinking water, in rat models of cancer in the mammary gland or colon. Solutions of 1.25% (w/v) black tea, or 1.85% (v/v) milk in tea were prepared three times per week. SD rats were given tea beginning at 42 days of age; one group was gavaged 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) at 49 days of age; another group received 8.4 mg 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) twice per week beginning at age 49, then 14 mg twice a week for 4 weeks more. The groups on DMBA were killed 33 weeks later, and those on IQ 39 weeks later. Tea decreased the mammary gland tumor multiplicity and volume, and milk and tea had a greater protective action. Male F344 rats were given two doses of 15 mg/kg azoxymethane (AOM) on weeks 6 and 7, and some groups started on tea, or tea and milk at 5 weeks; one group started on tea 2 days after AOM. Foci of aberrant crypts in the colon were decreased, after 9 weeks, in the groups on tea, or tea and milk during AOM administration, but not after AOM. Thus, tea decreases mammary tumor induction, and the production of foci of aberrant crypts in the colon. Milk potentiates these inhibiting effects.
The effects of green tea extract (GTE) on exogenous and endogenous models of rat liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2 for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA diet and simultaneously given GTE for 12 weeks. All rats were killed at the end of week 12. After DEN-initiation, the apparent numbers of glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, were decreased by the administration of GTE, though their sizes were not altered. In contrast, GTE did not significantly reduce the numbers of the lesions induced by the CDAA diet or affect their sizes. While the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE administration in both experimental models, GTE did not protect against the CDAA-diet-associated liver tissue damage in terms of either histology or plasma marker enzyme levels. We conclude that, while GTE may be a possible chemopreventive agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic hepatocyte damage, it does not significantly inhibit lesion development in hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.
The peroxynitrite scavenging activity of a series of structurally related flavonoids was tested. It was found that flavonoids are excellent scavengers of peroxynitrite. Compared to the known peroxynitrite scavenger ebselen, the most active flavonoids proved to be 10 times more effective. Indications were found that the catechol group (ring B) and the hydroxyl group at position 3 give the highest contribution to the peroxynitrite scavenging effect. The peroxynitrite scavenging is discussed in relation to the beneficial effect of flavonoid intake on the incidence of coronary heart disease.
Effects of green tea catechins on N-nitrosobis(2-oxopropyl)amine (BOP)-induced oxidative stress in pancreas and liver were examined. Hamsters were divided into two groups: one group was given free access to a 0.1% solution of green tea catechins as drinking water (c-ham) and the other to plain tap water (w-ham) for 1 week before subcutaneous injection of BOP 20 mg/kg body weight. Zero, 1, 2, 6, 12, 24, and 48 h after BOP injection, the pancreas and liver were excised and the tissue concentration of lipid peroxides (TBA values) and the amount of 8-hydroxydeoxyguanosine (8-OHdG) in nuclear DNA were measured. The concentration of lipid peroxides and the amount of 8-OHdG in the pancreas showed similar patterns of change between c- and w-ham. Soon after BOP injection, the concentration of lipid peroxides and the amount of 8-OHdG increased with a peak at 1 and 6 h, respectively. Their peak values of c-ham were significantly depressed compared with those of w-ham. Both levels returned to steady-state levels by 24 h. In the liver, the concentration of lipid peroxides and the amount of 8-OHdG were not affected by BOP administration. These results suggest that BOP induces oxidative damages in the target organ and oral intake of green tea catechins has a protective effect on the oxidative stress.
Nitric oxide (NO) plays an important role in inflammation and multiple stages of carcinogenesis. We investigated the effect of various tea polyphenols and caffeine on the induction of NO synthase (NOS) in thioglycollate-elicited and lipopolysaccharide (LPS)-activated peritoneal macrophages. Gallic acid (GA), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG), the major tea catechin, were found to inhibit inducible NOS (iNOS) protein in activated macrophages. EGCG, a potent antitumor agent with anti-inflammatory and antioxidant properties, inhibited NO generation, as measured by the amount of nitrite released into the culture medium. Inhibition of NO production was observed when cells were cotreated with EGCG and LPS. iNOS activity in soluble extracts of lipopolysaccharide-activated macrophages treated with EGCG (5 and 10 microM) for 6-24 hr was significantly lower than that in macrophages without EGCG treatment. Western blot, reverse transcription-polymerase chain reaction, and Northern blot analyses demonstrated that significantly reduced 130-kDa protein and 4.5-kb mRNA levels of iNOS were expressed in lipopolysaccharide-activated macrophages with EGCG compared with those without EGCG. Electrophoretic mobility shift assay indicated that EGCG blocked the activation of nuclear factor-kappaB, a transcription factor necessary for iNOS induction. EGCG also blocked disappearance of inhibitor kappaB from cytosolic fraction. These results suggest that EGCG decreases the activity and protein levels of iNOS by reducing the expression of iNOS mRNA and the reduction could occur through prevention of the binding of nuclear factor-kappaB to the iNOS promoter, thereby inhibiting the induction of iNOS transcription.
Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical tumor promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin-1 alpha (IL-1alpha) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theaflavine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1alpha mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against tumorigenesis. The results of this study suggest that black tea, specifically polyphenols present therein, may be useful against cutaneous inflammatory responses in human population.
Chronic inflammation has been implicated as the underlying factor in the pathogenesis of many disorders. In the past decade, inflammation-related endogenous production of reactive nitrogen species, similar to oxygen free radicals, has also been suggested as a risk factor for cancer, in addition to the well-studied exogenous nitroso compounds. Epidemiological, in vitro, and animal model studies have implicated green tea to be protective against nitroso compound-induced and inflammation-related cancer. Therefore, we investigated the effect of epigallocatechin-3-gallate (EGCG), one of the known biologically active catechins contained in green tea, on the production of nitric oxide (NO.). We have shown previously that EGCG reduces NO. production as measured by nitrite accumulation in the culture medium. Expanding on this finding, in this report we show that EGCG may do so by two mechanisms: reduction of inducible nitric oxide synthase (iNOS) gene expression and inhibition of enzyme activity. Addition of 1-10 microM EGCG to lipopolysaccharide- and interferon-gamma-activated mouse peritoneal cells reduced iNOS mRNA expression concentration dependently, to 82-14%, as measured by relative reverse transcription-polymerase chain reaction. Addition of 50-750 microM EGCG, in a concentration-dependent manner, inhibited the enzyme activity of iNOS, to 85-14%, and neuronal nitric oxide synthase (nNOS), to 93-56%, as measured by citrulline formation. EGCG competitively inhibited binding of arginine and tetrahydrobiopterin, and the gallate structure is important for this action.
The hypothesis that tea or dietary lipid-soluble antioxidants reduce atherogenesis by lowering the oxidizability of low-density lipoprotein (LDL) was investigated. Five groups of 20 female New Zealand white rabbits were fed a restricted amount of a high-fat (30 en%) semipurified diet supplemented with cholesterol (0.15%, w/w) for 21 weeks. The vitamin E content of the control diet was 40 mg/kg diet. The animals received either green tea or black tea in their drinking water or vitamin E (200 mg/kg diet) or beta-carotene (20 mg/kg). The serum cholesterol concentrations (in the order of 18-23 mmol/l) were not significantly different between the groups. Vitamin E was substantially increased as compared to controls in vitamin E supplemented animals (3-fold within 8 weeks in plasma and LDL; P < 0.01) and weakly (1.2-fold) by green and black tea (P < 0.05). Green tea consumption tended to reduce aortic lesion formation by 31% (24 +/- 3.2% versus 35 +/- 5.7% for control animals P = 0.11), while black tea, vitamin E and beta-carotene had no effect. This was in contrast to the resistance of isolated LDL to oxidation induced at high copper concentration. Green and black tea induced a 13% and 15% (P < 0.05) prolongation of the lag phase, respectively, with a correspondingly lower oxidation rate, while vitamin E increased the lag phase by 63% (P < 0.01) with a concomitant diminution of the oxidation rate and beta-carotene had no effect. Regression analysis showed that there was no relationship between the extent of atherosclerosis and LDL oxidizability or plasma malondialdehyde as marker of in vivo lipid peroxidation. The results of the present study raise the question whether LDL oxidizability (at least when tested at high induction rate ex vivo) is a primary causal mechanism in atherosclerosis in the cholesterol-fed rabbit. The suitability of the cholesterol-fed rabbit with extreme hypercholesterolaemia as a model to study antiatherosclerotic properties of dietary antioxidants, such as the tested polyphenols, is discussed.
The effect of consuming red wine, or its major polyphenol constituents catechin or quercetin, on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidation and to aggregation, was studied in atherosclerotic apolipoprotein E deficient (E degree) mice. Forty E degree mice at the age of 4 weeks were divided into four groups, 10 mice in each group, and were supplemented for up to 6 weeks in their drinking water with placebo (1.1% alcohol); catechin or quercetin (50 micrograms/d per mouse), or red wine (0.5 mL/d per mouse). Consumption of catechin, quercetin, or red wine had no effect on plasma LDL or HDL cholesterol levels. The atherosclerotic lesion area was smaller in the treated mice by 39%, 46%, and 48%, respectively, in comparison with E degree mice that were treated with placebo. In accordance with these findings, cellular uptake of LDL derived after catechin, quercetin, or red wine consumption was found to be reduced by 31%, 40%, and 52%, respectively. These results were associated with reduced susceptibility to oxidation (induced by different modes such as copper ions, free radical generator, or macrophages) of LDL isolated after red wine or quercetin and, to a lesser extent after catechin consumption, in comparison with LDL isolated from the placebo group. Similar results were obtained when LDL was preincubated in vitro with red wine or with the polyphenols prior to its oxidation. Even in the basal oxidative state (not induced oxidation), LDL isolated from E degree mice that consumed catechin, quercetin, or red wine for 2 weeks was found to be less oxidized in comparison with LDL isolated from E degree mice that received placebo, as evidenced by 39%, 48%, and 49% reduced content of LDL-associated lipid peroxides, respectively. This effect could be related to enhanced serum paraoxonase activity in the polyphenol-treated mice. LDL oxidation was previously shown to lead to its aggregation. The present study demonstrated that the susceptibility of LDL to aggregation was reduced in comparison with placebo-treated mice, by 63%, 48%, or 50% by catechin, quercetin, and red wine consumption, respectively, and this effect could be shown also in vitro. The inhibition of LDL oxidation by polyphenols could be related, at least in part, to a direct effect of the polyphenols on the LDL, since both quercetin and catechin were found to bind to the LDL particle via the formation of an ether bond. We thus conclude that dietary consumption by E degree mice of red wine or its polyphenolic flavonoids quercetin and, to a lesser extent, catechin leads to attenuation in the development of the atherosclerotic lesion, and this effect is associated with reduced susceptibility of their LDL to oxidation and aggregation.
To assess the blood concentration of catechins following green or black tea ingestion and the effect of addition of milk to black tea.
Twelve volunteers received a single dose of green tea, black tea and black tea with milk in a randomized cross-over design with one-week intervals. Blood samples were drawn before and up to eight hours after tea consumption.
The study was performed at the Unilever Research Vlaardingen in The Netherlands.
Twelve healthy adult volunteers (7 females, 5 males) participated in the study. They were recruited among employees of Unilever Research Vlaardingen.
Green tea, black tea and black tea with semi-skimmed milk (3 g tea solids each).
Consumption of green tea (0.9 g total catechins) or black tea (0.3 g total catechins) resulted in a rapid increase of catechin levels in blood with an average maximum change from baseline (CVM) of 0.46 micromol/l (13%) after ingestion of green tea and 0.10 micromol/l (13%) in case of black tea. These maximum changes were reached after (mean (s.e.m.)) t=2.3 h (0.2) and t=2.2 h (0.2) for green and black tea respectively. Blood levels rapidly declined with an elimination rate (mean (CVM)) of t1/2=4.8 h (5%) for green tea and t1/2=6.9 h (8%) for black tea. Addition of milk to black tea (100 ml in 600 ml) did not significantly affect the blood catechin levels (areas under the curves (mean (CVM) of 0.53 h. micromol/l (11%) vs 0.60 h. micromol/l (9%) for black tea and black tea with milk respectively.
Catechins from green tea and black tea are rapidly absorbed and milk does not impair the bioavailability of tea catechins.
Lipoprotein oxidation may contribute to development of atherosclerosis, and supplementation with antioxidants may reduce risk for atherosclerotic events. Genistein, a major isoflavone from soy protein, and catechins from green tea have important antioxidant properties. This study compared the effects of various diets containing antioxidant-rich foods or supplements on serum lipids and lipoprotein oxidation of male Sprague-Dawley rats. The control diet used was devoid of vitamin E. Test diets included these ingredients: green tea powder, 20 g/kg; β-carotene, 250 mg/kg; a low isoflavone soy protein isolate; a genistein-rich soy protein isolate; and vitamin E, 4000 mg/kg. Ten-week-old rats were acclimatized for 1 week on a special custom diet without vitamin E. Following randomization and allocation to different diet groups, rats were fed the test diets for 3 weeks. Blood was drawn by cardiac puncture, and the plasma was separated by centrifugation. The VLDL-LDL fraction was isolated by ultracentrifugation. Oxidation kinetics of the VLDL-LDL fraction were determined by measuring the lag phase and formation of conjugated dienes, lipid peroxides, and TBARS.
There is considerable epidemiological evidence that tea drinking lowers the risk of heart disease. However, the mechanism by which tea can be protective is unknown. Hamsters were fed a normal or high cholesterol diet for 2 weeks and drank green or black tea ad libitum. The plasma lipid profile was significantly improved by both teas compared to controls. Also in vivo lipid oxidation as measured by plasma lipid peroxides and LDL+VLDL oxidizability were significantly decreased by the teas. In the normal fed tea groups fibrinogen was decreased but not in the high cholesterol groups. Green tea was significantly more effective than the black tea. These results show in the hamster model that black and green tea improve the risk factors for heart disease by both hypolipemic and antioxidant mechanisms and possibly a fibrinolytic effect.
Oxidized low density lipoprotein (LDL) promotes atherogenesis. Although pharmacological antioxidants such as probucol inhibit both LDL oxidation and atherosclerosis in hyperlipidemic animals, the effects of natural antioxidants such as vitamin E are inconclusive. To further determine the effects of supplemental dietary antioxidants in vivo, we evaluated whether combined dietary antioxidants (0.1% vitamin E, 0.5% beta-carotene, and 0.05% vitamin C) inhibit LDL oxidation and fatty streak lesion development in homozygous LDL receptor-null (LDLR-/-) mice fed a high-fat, high-cholesterol diet. An additional group of mice were fed black tea, which has been shown to inhibit LDL oxidation in vitro. After receiving a high-fat, high-cholesterol diet for 8 weeks, the combined antioxidant-supplemented (antioxidant) group (n=18), tea group (n=19), and control group (n=17) had equivalent plasma cholesterol levels. LDL oxidation, as measured by the lag phase of conjugated diene formation, was markedly inhibited in the antioxidant group compared with the tea or control groups [mean lag phases=143+/-7 (antioxidant), 100+/-5 (tea), and 84+/-4 (control) minutes; P<0.0001 antioxidant versus tea or control]. The cross-sectional surface area of fatty streak lesions in the aortic sinus was reduced by 60% in the antioxidant group compared with both the tea and control groups (P<0.0001 antioxidant versus tea or control). There was no difference in lesion area between tea and control groups. Although both LDL oxidation and atherosclerosis were significantly inhibited in the antioxidant group, no correlation between lag phase values and lesion size was observed among individual animals. Furthermore, black tea did not inhibit fatty streak development in LDLR-/- mice. These data suggest that combined natural dietary antioxidants inhibit both LDL oxidation and atherogenesis in animals with elevated LDL but that inhibition of LDL oxidation alone may not prevent the development of atherosclerosis.
To evaluate the benefit of green tea in mitigating hazards caused by repeated exposure of 2-nitropropane (2NP), we examined the effects of the tea on toxic indices, oxidative DNA damage and cell proliferation in the liver of 2NP-treated rats. Male Fischer 344 rats were administered, by gastric intubation, a total of six doses of 60 mg/kg 2NP(L), or alternatively two doses of 90 mg/kg and then four doses of 120 mg/kg 2NP(H) during 2 weeks. Green tea infusion was given to the rats as drinking water 1 week before the 2NP treatments and throughout the experiment. Significant elevation of hepatotoxic indices was evident in the 2NP(H)-treated group, such as an increase of serum glutamic-oxaloacetic transaminase (GOT) activity and of hepatic lipid peroxidation, together with a decrease in hepatic glycogen and serum triglyceride, and degenerative changes in the hepatocytes. A dose-related increase was observed in oxidative DNA damage and cell proliferation in the liver. Green tea effectively inhibited all of above changes induced by 2NP treatment, suggesting that tea intake may be effective for preventing the hepatic injuries after chronic exposure to 2NP.
Consumption of tea, especially green tea, has been shown to reduce the incidence of ultraviolet (UV)-related skin tumors in hairless mice. Because milk is added to much of the tea consumed in Western cultures, we have studied the effects of including milk in the tea consumed by hairless mice receiving simulated solar radiation. Under these conditions, mice consuming tea with 10% whole milk had 30% fewer papillomas, 50% fewer tumors, and 55% smaller lesions than mice consuming water. Mice consuming tea alone had fewer papillomas and tumors than mice consuming tea with milk; however, the difference in area affected was not statistically significant. In separate experiments, there was a significant dose response to black tea as a preventive against UV-related skin lesions, and also consumption of black tea was associated with a small but significant reduction in the incidence of papillomas in mice previously exposed to UV radiation. The results of these studies demonstrate that, in hairless mice, black tea can inhibit the formation of UV-induced skin tumors in a dose-dependent manner and, even with the addition of milk, can still inhibit the growth of UV-related skin tumors.