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Suppressive effects of Okinawan food items on free radical generation from stimulated leukocytes and identification of some active constituents: implications for the prevention of inflammation-associated carcinogenesis
Abstract
Okinawa prefecture in Japan is a distinct area characterized by unique traditional food habits and longevity. Prolonged exposure to activated leukocytes, playing pivotal roles in chronic inflammation-associated carcinogenesis, is known to lead to oxidative and nitrosative damage to macromolecules in the body since they are primary sources of free radicals, such as superoxide anion (O(2)(-)) and nitric oxide (NO). In this study, we estimated anti-oxidative and anti-nitrosative activities of Okinawan food items by employing two cellular experimental systems: (1) phorbol ester-induced O(2)(-) generation from differentiated HL-60 human promyelocytic leukemia cells; and (2) lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A total of 138 food items, consisting of 42 samples unique to Okinawa and 96 common in the Japanese main island, were purchased at local markets in Okinawa and extracted with chloroform. When tested at a concentration of 100 microg/ml, 38% (16/42) of the former showed 70% or more inhibition of O(2)(-) generation while 21% (20/96) of the latter did so. In parallel, 64% (27/42) of the former showed significant NO generation suppression in contrast to 48% (46/96) of the latter . Twenty-one active species were further tested at a concentration of 20 mug/ml, and eleven species, including sugar cane, wild turmeric, and zedoary, were indicated to be most promising items with anti-oxidative and anti-nitrosative properties. In addition, some of the active constituents (chebulagic acid, a resveratrol derivative, and sesquiterpenoids) were identified. Our results suggest that food items typical in the Okinawa area have higher cancer preventive potential than those common in Japan.
... It may be useful in therapy of diseases of chronic inflammation to use these three classes of Nrf2 raising nutrients, because the higher rates of oxidation of these nutrients in inflamed, oxidative stressed tissues may act to counteract otherwise lowered Nrf2 responses in such tissues. The traditional Mediterranean diet which is thought to be ideally the Cretan diet and perhaps the southern Greek and southern Italian diets of the 1960s and the traditional Okinawan diet of the same time period, are thought to be the most healthful human diets known, with high overall lifespans, large numbers of centenarians and low incidences of cancer and cardiovascular disease [96][97][98][99][100][101][102][103] . Diets in both of these locations are thought to have become much less healthful in recent decades, but studies of these two traditional diets are still important parts of our understanding of dietary factors that may influence human health. ...
... Consequently, it may be argued that the best diets for raising Nrf2 are diets with regular seafood consumption but otherwise containing large amounts of foods derived from plants, particular plants with low calorie densities which are likely to be consumed in larger quantities and therefore provide, in general more phytochemicals. Both the traditional Mediterranean and Okinawan diets clearly fit this description [96][97][98][99][100][101][102][103] . Furthermore several of the nutrient categories known to raise Nrf2 listed in Table 2 are thought to be high in each of these diets (see Table 3). ...
... All sweet potatoes are very high in carotenoids and purple sweet potatoes are very high in anthocyanin phenolics which are potent Nrf2 activators. Murakami et al. [97] showed that a large number of specific vegetables in the traditional Okinawan diet are potent agents that lower the production of both superoxide and nitric oxide in leukocytes, suggesting that these vegetables act in part by raising Nrf2. In some cases, they [97] implicated both phenolics and terpenoids in producing these responses, again suggesting a possible Nrf2 effect. ...
The transcription factor Nrf2, nuclear factor erythroid-2-related factor 2, activates the transcription of over 500 genes in the human genome, most of which have cytoprotective functions. Nrf2 produces cytoprotection by detoxification mechanisms leading to increased detoxification and excretion of both organic xenobiotics and toxic metals; its action via over two dozen genes increases highly coordinated antioxidant activities; it produces major anti-inflammatory changes; it stimulates mitochondrial biogenesis and otherwise improves mitochondrial function; and it stimulates autophagy, removing toxic protein aggregates and dysfunctional organelles. Health-promoting nutrients and other factors act, at least in part by raising Nrf2 including: many phenolic antioxidants; gamma- and delta-tocopherols and tocotrienols; long chain omega-3 fatty acids DHA and EPA; many carotenoids of which lycopene may be the most active; isothiocyanates from cruciferous vegetables; sulfur compounds from allium vegetables; terpenoids. Other health promoting, Nrf2 raising factors include low level oxidative stress (hormesis), exercise and caloric restriction. Raising Nrf2 has been found to prevent and/or treat a large number of chronic inflammatory diseases in animal models and/or humans including various cardiovascular diseases, kidney diseases, lung diseases, diseases of toxic liver damage, cancer (prevention), diabetes/metabolic syndrome/obesity, sepsis, autoimmune diseases, inflammatory bowel disease, HIV/AIDS and epilepsy. Lesser evidence suggests that raising Nrf2 may lower 16 other diseases. Many of these diseases are probable NO/ONOO(-) cycle diseases and Nrf2 lowers effects of NO/ONOO(-) cycle elements. The most healthful diets known, traditional Mediterranean and Okinawan, are rich in Nrf2 raising nutrients as apparently was the Paleolithic diet that our ancestors ate. Modern diets are deficient in such nutrients. Nrf2 is argued to be both lifespan and healthspan extending. Possible downsides to too much Nrf2 are also discussed. Nrf2 is not a magic bullet but is likely to be of great importance in health promotion, particularly in those regularly exposed to toxic chemicals.
... Interestingly, Kuroda et al. recently reported that an ethanol extract from turmeric containing CUR, demethoxycurcumin, bisdemethoxycurcumin, and the sesquiterpene, ar-turmerone (ATM) significantly suppressed increases in blood glucose in type 2 diabetic KK-A(y) mice [16]. In addition, other authors have shown that TUR are capable of suppressing endotoxin-induced nitric oxide (NO) generation by mouse macrophage, with an efficacy comparable to that of CUR [17]. Although the in vitro apoptosis-inducing properties of TUR components have been recently documented [18], no in vivo studies in regard to cancer prevention have been reported. ...
... Lipopolysaccharide (LPS) (Escherichia coli serotype 0127, B8) came from Difco Labs (Detroit, MI). ATM was purified as previously reported [17]. CUR used in the in vivo (purity: 75%) and in vitro (purity: 90%) experiments was from Cayman Chemical (Ann Arbor, MI). ...
... Inflammatory cells, which are known to induce excess NO generation, play pivotal roles in the development of inflammationassociated colon carcinogenesis [20]. On the other hand, we previously reported that TUR including ATM decreased NO generation in LPS-stimulated RAW264.7 mouse macrophages, though the mechanism of action was not addressed [17]. In the present study, we pretreated RAW264.7 cells with the vehicle, ATM, or CUR for 30 min then exposed them to LPS for 6 h, after which mRNA expressions of iNOS and COX-2 were examined by RT-PCR. ...
Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. © 2012 BioFactors, 2013.
... Продукты с Окинавы, как правило, обладают более сильными свойствами по удалению свободных радикалов. Из 138 пищевых продуктов, проверенных на противовоспалительное действие, многие оказались многообещающими, особенно дикая куркума и zedoary (белая куркума) [50]. К таким продуктам можно отнести и сладкий картофель (и его листья), горькую дыню, морские водоросли и другие [47,50]. ...
... Из 138 пищевых продуктов, проверенных на противовоспалительное действие, многие оказались многообещающими, особенно дикая куркума и zedoary (белая куркума) [50]. К таким продуктам можно отнести и сладкий картофель (и его листья), горькую дыню, морские водоросли и другие [47,50]. ...
The population of Japan and Okinawa is known for the longest life expectancy, which many researchers rightly associate with the nature of nutrition existing in these territories. The Japanese diet and Okinawan diet, along with other traditional diets, are real examples of historically established sustainable patterns of healthy eating. Asian eating styles have marked differences from European eating patterns, not only in differences in food sources, but also in eating habits. The article presents the historical, climatic and cultural features of these diets; the issues of food composition, energy and nutritional value of these models of nutrition are considered in detail with an analysis of the differences existing between them; highlights the benefits of products grown mainly in Japan, which are ration-forming for the population of this country; as well as the results of scientific studies on the protective effect of the Japanese and Okinawan diets on human health and disease prevention.
... CA has been shown to inhibit ROS generation [33] and anti-hyperglycemic activity [34]. CA was also reported to alleviate arthritis in mice models [35] and inhibited LPS-induced Nitric oxide [36]. CA and punicalagin were shown to inhibit HSV-1 entry in A549 human lung cells by preventing binding, penetration, and cell-to-cell spread [37]. ...
... Our group has shown CA isolated from Terminalia chebula inhibits LPS induced inflammation [28], inhibits proliferation of colon cancer cells [29]. In addition to these properties several groups have shown beneficial properties of CA [33][34][35][36][37]. Current therapies to retinoblastoma are limited necessitating the patient to undergo enucleation. ...
Background
Plants are the valuable source of natural products with important medicinal properties. Most of the approved anti cancer drugs have a natural product origin or are natural products. Retinoblastoma is the most common ocular cancer of children. Although chemotherapy is the preferred mode of therapy, a successful treatment for retinoblastoma requires enucleation. Chebulagic acid (CA) from Terminalia chebula was shown to have anti-proliferative properties in the studies on cancerous cell lines. Due to anti cancer properties of CA and due to limitation in treatment options for retinoblastoma, the present study is undertaken to understand the role of CA on the proliferation of retinoblastoma cells.
Methods
Anti proliferative potential of CA was determined by MTT assay. The expression levels of various cell death mediators in retinoblastoma cells with CA treatment were assessed by Western blotting. Flowcytometer analysis was used to estimate the mitochondrial membrane potential (MMP) and to determine the percentage of cells undergoing apoptosis.
Results
The present study showed CA inhibited the proliferation of retinoblastoma cells in a dose dependent manner. CA modulated MMP, induced release of Cytochrome c, activated caspase 3 and shifted the ratio of BAX and Bcl2 towards cell death. G1 arrest, noticed in CA treated cells, is mediated by the increase in the expression of CDK inhibitor p27. CA treatment also decreased the levels of NFκB in the nucleus. This decrease is mediated by suppression in degradation of IκBα.
Conclusion
CA has shown significant anti proliferative potential on retinoblastoma cells. Our findings clearly demonstrate that CA induces G1 arrest, inhibits NFκB and induces apoptosis of retinoblastoma cells.
... CA has been shown to inhibit a-glucosidase activity [16], ROS generation from PMA-stimulated leukocytes [17] and CTL-mediated cytotoxicity [18]. In addition, it has been reported to suppress arthritis in mice [19] and LPS-induced nitric oxide (NO) generation in RAW 264.7 mouse macrophage cells [20]. However the detailed molecular anti-inflammatory mechanism has not yet been studied. ...
... In the present study, we found that CA potently inhibited the production of NO and prostaglandin E 2 (PGE 2 ) in a concentrationdependent manner. To examine the potential anti-inflammatory properties of CA on LPS-induced NO and PGE 2 production in RAW 264.7 cells, cells were treated with or without CA (5,10,15,20 and 25 lM) for 1 h and then treated with LPS (1 lg/ml) for 16 h. ...
Chebulagic acid (CA), a natural anti-oxidant, showed potent anti-inflammatory effects in LPS-stimulated RAW 264.7, a mouse macrophage cell line. These effects were exerted via inhibition of NO and PGE2 production and down-regulation of iNOS, COX-2, 5-LOX, TNF-alpha and IL-6. CA inhibited NF-kappaB activation by LPS, and this was associated with the abrogation of IkappaB-alpha phosphorylation and subsequent decreases in nuclear p50 and p65 protein levels. Further, the phosphorylation of p38, ERK 1/2 and JNK in LPS-stimulated RAW 264.7 cells was suppressed by CA in a concentration-dependent manner. LPS-induced generation of reactive oxygen species (ROS) was also effectively inhibited by CA. These results suggest that CA exerts anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages by inhibition of NF-kappaB activation and MAP kinase phosphorylation.
... Antibodies were purchased from the following sources: rabbit anti-CD74 was from Santa Cruz Biotechnology Inc. (Santa Cruz, CA), α-tublin came from Calbiochem (San Diego, CA), and anti-rabbit IgG was obtained from Dako (Glostrup, Denmark). 1'-Acetoxychavicol acetate (ACA) [13], zerumbone [14], auraptene [15] , nobi- letin [16], and ar-turmerone [17] were isolated as previously described. PEITC (phenetyl isothiocyanate) and BUITC (butenyl isothiocyate) were purchased from Tokyo Chemical Industry (Tokyo, Japan). ...
... fetal gastric cells. Screening of selected food factors for their effects on CD74 expression using novel cell-based ELISA with N87 cells A total of 25 food factors (Fig. 2) were selected based on their previously reported anti-inflammatory in vitro and in vivo activities [17,202122. Each was subjected to our novel cell-based ELISA established in the present study. ...
Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4-100 microM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC(50)/IC(50) value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.
... A large body of evidence shows that lifestyle and dietary habits, in particular, play some predominant role in the onset of many malignancies, including CRC [22]. On the other hand, cancer prevention using food phytochemicals obtained from biologically active plants is an attractive and reasonable strategy, especially when considering traditional uses in local remedies as well as the unique dietary habits of indigenous populations [23]. Indeed, the active constituents of spices and herbs have been shown to have marked potential for cancer prevention [24]. ...
Colorectal cancer (CRC) ranks among the most frequently diagnosed malignancies and is associated with a significantly high mortality rate. In recent years, increasing attention has been directed toward naturally derived substances with anticancer properties. In our study, we focused on determining the biological and antibacterial effects of selected essential oils (EOs)—peppermint, oregano, tea tree, lemon, lavender, frankincense, and oil blends (Zengest and OnGuard). Analyses were performed on human colon carcinoma cell lines (HCT-116 and HT-29). The cytotoxic (MTT assay), genotoxic effects (comet assay), and reactive oxygen species levels (ROS-Glo™ H2O2 Assay) of EOs and oil blends were determined. In our study, we found that all of the studied oils have the potential cyto/genotoxic effects on CRC cell lines after 24 h exposure. The results revealed that oregano, Zengest, and frankincense showed statistically the highest cytotoxic effects [IC50 0.05 µg/mL] compared to the other studied oils. These oils induced DNA damage and also increased ROS levels. On the other hand, peppermint was shown to have the lowest cytotoxic effect [IC50 0.67 µg/mL] on the HT-29 cell line. We also evaluated the antibacterial effects of oregano, tea tree, and the OnGuard blend, determining their impact on the viability of beneficial bacteria models, including Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Lactobacillus brevis, Lactobacillus pentosus, and Weizmannia coagulans. Oregano exhibited strong antibacterial activity, with an inhibition zone of 31 mm, while tea tree and OnGuard showed inhibition zones ranging from 12 to 15 mm. The EOs (oregano, tea tree, OnGuard) demonstrated antibacterial effects, with MICs ranging from 0.05 to 0.5 µg/mL. Peppermint, lemon, lavender, frankincense, and the Zengest blend did not inhibit the growth of lactic acid bacteria or W. coagulans, and thus did not impact bacterial survival. On the other hand, they demonstrated potential anticancer effects.
... They recognize the Sabbath, and "downshift" for twenty-four hours every week [40]. The Okinawan 7 diet is low calorie with reduced fatty acid consumption [51,52]. The diet is rich in seaweed (sea vegetables), Okinawan tofu, bitter melon, lots of vegetables, soy products, sweet potatoes, turmeric, seafood such as fish, and pork [53][54][55]. ...
Adherence to the Mediterranean diet has been shown to lower the risk of developing chronic non-communicable diseases like cardiovascular and neurodegenerative diseases and cancer. Improvements in depression, participation in daily activities in older individuals, weight loss and reduction in adverse pregnancy outcomes are associated with adherence to the Mediterranean diet. The number of studies that have evaluated barriers to the adherence of the Mediterranean diet in the US and in particular, in racial and ethnic minority populations within the US are few. Among Native American and Alaskan Native populations, studies evaluating traditional or alternative Mediterranean diet adherence for chronic non-infectious diseases is unavailable. Mediterranean diet scoring instruments used in studies in European and Mediterranean countries and among white participants in the US fail to capture the dietary patterns of racial and ethnic minority populations. In this narrative review the food components of the traditional Mediterranean diet are discussed, adherence to the Mediterranean diet is examined in Mediterranean and non-Mediterranean countries and barriers preventing adherence to the Mediterranean diet in the US and among racial and ethnic minority populations is reviewed. Recommendations for improving nutrition education and intervention, and increasing adherence and cultural adaptions to the Mediterranean diet are provided.
... T. chebula fruits have been used in various preparations of Ayurvedic medicines to treat several diseases such as coronary disorders, digestive and allergic problems, and infectious diseases such as cough and skin disorders [6] reported that CA inhibits the cytotoxic T-lymphocyte-mediated cytotoxicity and suppresses arthritis in mice [7] and lipopolysaccharides (LPS)-induced nitric oxide generation in RAW 264.7 mouse macrophage cells. [8] Gao et al. also described that CA inhibits the ROS production in phorbol myristate acetate-stimulated leukocytes and alpha-glycosidase activity. [9] Reddy et al. [10] demonstrated that the anti-inflammatory effect of CA was mediated by suppression of nuclear factor kappa B and mitogen-activated protein kinase activation in LPSinduced mouse macrophage cells -RAW 264.7. ...
Background: Prostate cancer (PCa) is the second most typical cancer and also the sixth leading reason behind cancer death among men worldwide with associate degree calculable recorded amount of 1.1 million cases and 307,000 deaths in 2012.
Chebulagic acid (CA), a benzopyran tannin, is one of the major bioactive compounds present in the fruits of Terminalia chebula. Aim: The present study was aimed at assessing the effects of CA on proapoptotic (Bax) and antiapoptotic protein molecules such as B-cell lymphoma-2 (Bcl-2) and Bcl-extra large (Bcl-xl) in PC-3 cell line. Materials and Methods: Antiproliferative potential of CA was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. PC-3 cells were treated with different concentration of CA (1, 5, 10, 25, 50, and 100 µM). Pro- and anti-apoptotic proteins were done by western blotting methods. PC-3 cells were treated with the treatment of CA resulted in a dose-dependent inhibition of the growth of PC-3 cells. This was associated with increased levels of proapoptotic protein (Bax) and the reduced levels of the antiapoptotic proteins Bcl-2 and Bcl-xL. Conclusion: The present findings clearly suggest that CA induces apoptosis by the regulating intrinsic pathways which could be very useful for the treatment of PCa.
... ROS generation from PMA (Phorbol 12-myristate 13-acetate)-stimulated leukocytes (Kinoshita et al. 2007) and CTL-mediated cytotoxicity (Hamada et al. 1997). In addition, it has been reported to suppress arthritis in mice (Lee et al. 2005) and LPS-induced nitric oxide (NO) generation in RAW 264.7 mouse macrophage cells (Murakami et al. 2005). However, the detailed molecular anti-inflammatory mechanism has not yet been studied. ...
The aim of the present study was to evaluate the hepatoprotective, antioxidant, and anti-inflammatory potential of chebulagic acid on carbon tetrachloride–induced hepatic fibrosis in rats. The liver was damaged in the rats using CCL4 (2 ml/kg b.w dissolved in 20% corn oil) intragastrically twice/week for 8 weeks. After 8 weeks, activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase, lipid peroxidation markers, and enzymic and non-enzymic antioxidant enzymes, inflammatory and anti-inflammatory cytokines were analyzed and all these parameters were altered. Chebulagic acid administration reversed all the altered parameters to near-normal levels. Improved histological and immunohistochemical observations liver supported the biochemical investigated. Hence, chebulagic acid exhibits hepatoprotective effects against CCl4-induced liver damage.
... While aqueous extracts have been characterized in depth for either their in vivo activity or their antioxidant components (such as phenols and polyphenols, amino acid-like mycosporines, and sulfated polysaccharides), scarce information exists for the apolar organic-produced fraction, like the one we produced in this study. In the red seaweed Gracilaria blodgetti, a chloroform extract could decrease the oxidative stress induced in leukocytes [94][95][96][97]. These results indicate that apolar extracts can be a source of antioxidants for biological membranes. ...
The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex
®
), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex
®
improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex
®
is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex
®
possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.
... The relatively few whole diet studies that have assessed immune cells, including expression of adhesion markers or cytokine secretion, have been short in duration (typically 3 months) and have predominantly been conducted in Mediterranean (MED) countries such as Spain or Italy (25)(26)(27). A limited number of studies have investigated the Okinawan diet and New Nordic Diet but currently there is no evidence of immune modulation (28)(29)(30)(31). Based on the current evidence of the positive health benefits of the MED diet in reducing cardiovascular risk factors, and expression of inflammatory mediators (25-27, 32, 33), predominantly in an elderly population, this diet has the potential to improve immune health. ...
Introduction
Aging is accompanied by increased susceptibility to infection and age-associated chronic diseases. It is also associated with reduced vaccine responses, which is often attributed to immunosenescence and the functional decline of the immune system. Immunosenescence is characterized by a chronic, low-grade, inflammatory state termed inflammaging. Habitants of Mediterranean (MED) regions maintain good health into old age; often attributed to MED diets.
Hypothesis
Adoption of a MED-diet by elderly subjects, in Norfolk (UK), may improve immune responses of these individuals and in particular, dendritic cell (DC) function.
Experimental approach
A total of 120 elderly subjects (65–79 years old) recruited onto the Nu-AGE study, a multicenter European dietary study specifically addressing the needs of the elderly, across five countries, and were randomized to the control or MED-diet groups, for one year. Blood samples were taken pre- and post-intervention for DC analysis and were compared with each other, and to samples obtained from 45 young (18–40 years old) subjects. MED-diet compliance was assessed using high performance liquid chromatography-with tandem mass spectrometry analysis of urine samples. Immune cell and DC subset numbers and concentrations of secreted proteins were determined by flow cytometric analysis.
Results
As expected, reduced myeloid DC numbers were observed in blood samples from elderly subjects compared with young. The elevated secretion of the adipokine, resistin, after ex vivo stimulation of peripheral blood mononuclear cells from elderly subjects, was significantly reduced after MED-diet intervention.
Conclusion
This study provides further evidence of numerical and functional effects of aging on DCs. The MED-diet showed potential to impact on the aging immune cells investigated and could provide an economical approach to address problems associated with our aging population.
... Compounds that have potential CR-mimetic properties, such as carotenoids, flavonoids and other phytochemicals, are synthesized by plants to help scavenge free radicals formed due to stress from extremes of heat, cold, insects, UV light or other threats that are common to sub-tropical Okinawa. Murakami et al. [82] investigated typical food items from Okinawa and compared them to food items from mainland Japan and found that foods from Okinawa had, on average, stronger free radical scavenging properties. Of over one hundred food items tested for anti-oxidative and antinitrosative activity, many were shown to be promising antiinflammatory agents, with implications for the prevention of inflammation-associated carcinogenesis, especially two kinds of turmeric, wild Okinawan turmeric (Curcuma aromatica) and Okinawan zedoary (Curcuma zedoaria); and 'Botanbofu' or 'Sakuna' as it is known in Okinawa (Peucedanum japonicum). ...
The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects of individual nutrients at the cellular and molecular levels. This approach has appropriately expanded in recent years to become more holistic with the aim of understanding the role of nutrition in the broader context of dietary patterns. Ultimately, this approach will culminate in a full understanding of the dietary landscape-a web of interactions between nutritional, dietary, social, behavioral and environmental factors-and how it impacts health maintenance and promotion.
... CA inhibits the activity of ␣-glucosidase (Gao et al. 2007), generation of reactive oxygen species (ROS) from phorbol 12-myristate 13-acetate (PMA) stimulated leukocytes (Kinoshita et al. 2007), and cytotoxic T lymphocyte (CTL) mediated cytotoxicity (Hamada et al. 1997). Additionally, CA has been shown to suppress arthritis in mice as well as lipopolysaccharide (LPS) induced nitric oxide generation in RAW 264.7 mouse macrophage cells (Murakami et al. 2005). It is a COX-2 and 5-LOX dual inhibitor and induces anti-proliferative effects in various human cancer cell lines ). ...
Inhibition of angiogenesis is a useful strategy to prevent cancer growth by targeting new vessels that grow to nourish actively proliferating tumor cells. Endothelial cells can use a number of different pathways to cause angiogenesis, and each step in these pathways can be targeted. The use of multi-targeted drugs is gaining much importance in this scenario. Our previous results have shown that chebulagic acid (a benzopyran tannin present in the fruits of Terminalia chebula) has anti-angiogenic properties. Thus, this study was designed to examine the molecular mechanism for the anti-angiogenic effects of chebulagic acid. Results from our investigations using molecular docking studies and human umbilical vein endothelial cells in culture suggested that chebulagic acid inhibits both GSK-3β-dependent β-catenin phosphorylation (an important mediator of VE-cadherin–β-catenin signaling) and VEGFR2 phosphorylation, which is an important step in VEGF signaling. Chebulagic acid inhibits angiogenesis by blocking both the VEGF–VEGFR2 complex and cell–cell contact dependent downstream signaling pathways.
... In this system, intracellular reactive oxygen species generation is detected by a nitroblue tetrazolium (NBT) reduction method [16]. Briefly, HL-60 cells (5 × 10 5 cells/ml) were incubated in RPMI 1640 medium supplement with 10% heated fetal bovine serum, 50 IU/ml penicillin and 50 µg/ ml streptomycin containing 1.3% dimethylsulfoxide (DMSO) for 6 days [17]. Differentiated HL-60 cells (1 × 10 6 ) were incubated with 500 µl of various dilutions of the extracts, and then incubated for 15 min. ...
Dried stems and leaves of Yha-nang dang (Bauhinia strychnifolia Craib.) have long been used in Thailand to make tea for promoting health and for detoxification of the body. The objectives of this study were to investigate antioxidant activities of B. strychnifolia dried stem and leaf extracts obtained by different extraction methods. The antioxidant power of B. strychnifolia extracts and water extracts of green tea leaves (Camellia sinensis) were evaluated using four different methods: DPPH radical scavenging assay, Ferric reducing antioxidant power (FRAP) assay, and Superoxide radical scavenging by NBT dye reduction assay, and measurement of total phenolic contents by the Folin-Ciocalteu colorimetric method. The 95% ethanolic extract of B. strychnifolia stems exhibited the strongest DPPH radical scavenging activity, with an EC50 value of 4.2 μg/ml. This was in agreement with results from the Ferric reducing antioxidant power assay, which showed that this extract had the highest FRAP value and TEAC (Trolox equivalent antioxidant capacity) values of 1481.2 mg Fe(II)/g and 421.4 mg Trolox/g, respectively. The 50% ethanolic extracts of B. strychnifolia stems showed the highest superoxide radical scavenging activities with an EC50 value of 85.7 μg/ml. The total phenolic contents of all extracts ranged from 143.7 to 390.1 mg GAE/g. The 95% ethanolic extract of B. strychnifolia stems had the highest total phenolic contents (390.1 mg GAE/g). Green tea water extracts showed less antioxidant activity than 95% ethanol B. strychnifolia stem extracts, by all assays, except by the DPPH assay. The results from this study indicate that ethanolic extracts of B. strychnifolia stems are rich in phenolic content and demonstrate as good, or better antioxidant activities compared to green tea. This lends scientific support for the use of these extracts for detoxification by Thai traditional medicine practitioners, and suggests that they could be further developed into commercial detoxification products.
... In this system, intracellular reactive oxygen species generation is detected by a nitroblue tetrazolium (NBT) reduction method [16]. Briefly, HL-60 cells (5 × 10 5 cells/ml) were incubated in RPMI 1640 medium supplement with 10% heated fetal bovine serum, 50 IU/ml penicillin and 50 µg/ ml streptomycin containing 1.3% dimethylsulfoxide (DMSO) for 6 days [17]. Differentiated HL-60 cells (1 × 10 6 ) were incubated with 500 µl of various dilutions of the extracts, and then incubated for 15 min. ...
Dried stems and leaves of Bauhinia strychnifolia Craib. have long been used in Thailand to make tea for promoting health and for detoxification of the body. The objectives of this study were to investigate antioxidant activities of B. strychnifolia dried stem and leaf extracts obtained by different extraction methods. The antioxidant power of B. strychnifolia extracts and water extracts of green tea leaves (Camellia sinensis) were evaluated using four different methods: DPPH radical scavenging assay [1], Ferric reducing antioxidant power (FRAP) assay[2], and Superoxide radical scavenging by NBT dye reduction assay[3], and measurement of total phenolic contents by the Folin-Ciocalteu colorimetric method [4]. The 95% ethanolic extract of B. strychnifolia stems exhibited the strongest DPPH radical scavenging activity, with an EC50 value of 4.21 ± 0.77 µg/ml. This was in agreement with results from the Ferric reducing antioxidant power assay, which showed that this extract had the highest FRAP value and TEAC (Trolox equivalent antioxidant capacity) values of 1481.21 ± 0.76 mg Fe(II)/g and 421.44 ± 1.87 mg Trolox/g, respectively. The 50% ethanolic extracts of B. strychnifolia stems showed the highest superoxide radical scavenging activities with an EC50 value of 85.69 ± 0.37 µg/ml. The total phenolic contents of all extracts ranged from 143.65 to 390.10 mg GAE/g. The 95% ethanolic extract of B. strychnifolia stems had the highest total phenolic contents (390.10 ± 1.25 mg GAE/g). Green tea water extracts showed less antioxidant activity than 95% ethanol Bauhinia stem extracts, by all assays, except by the DPPH assay. The results from this study indicate that ethanolic extracts of B. strychnifolia stems are rich in phenolic content and demonstrate as good, or better antioxidant activities compared to green tea.
Keywords: Bauhinia strychnifolia Craib, green tea extracts, antioxidant activity, total phenolic content
... It is also used in Brazilian religious afro-rituals 8 . This species is appreciated as spice and it has remarkable presence in traditional food habits of some Asian areas 9 . All parts from A. zerumbet plants are used: leaves, flowers and rhizomes. ...
Alpinia zerumbet (Zingiberaceae) is cultivated in several tropical areas. It has a high value all over the world as a spice in culinary preparations and for its medicinal properties. The composition of the essential oil obtained by simultaneous distillation-extraction (SDE) and hydrodistillation (HD) from fresh leaves of A. zerumbet was analyzed by GC-MS. In both samples the main constituents were terpinen-4-ol, 1,8-cinole, sabinene and λ-terpinene together with caryophyllene and caryophyllene oxide sesquiterpenes. However, individual percentage values of compounds varied between the methods. The components camphene (0.3 %), p-2-mentha-4(8)-diene (1.4 %) and trans-sabinene hydrate (1.0 %) were obtained only by SDE. Static-headspace (S-HS) was for the first time used to analyze the aroma from fresh leaves of A. zerumbet. Sabinene, 1,8 cineole and λ- terpinene were the main terpenes detected through S-HS. Flower oil was extracted by HD method, and the major components identified were 1,8 cineole (15.5 %), λ-terpinene (13.1 %) and terpinen-4- ol (42.3 %). There was a predominance of monoterpenes.
... The presence of flavonoids in rhizomes of A. calcarata, especially the labdane diterpene type, is widely distributed among Zingiberaceae (Hema & Nair, 2009). Another substance identified in some species is resveratrol, which is regarded as one of the dietary components of the Japanese living on Okinawa, thus potentially contributing to their longevity (Murakami et al., 2005). Species from the genus Alpinia are frequently used for their aromatic properties, which are related to volatile compounds that have been detected by different extraction techniques (De Pooter, 1995; Zoghbi et al., 1999; Joseph et al., 2001; Ali, et al., 2002; Mallavarapu et al., 2002; Fang et al., 2003; Elzaawely et al., 2007a; Victório et al. 2010b; 2010c; 2010d). ...
Plants containing bioactive substances have increasingly become the object of research studies, particularly those plants with therapeutic value. Many species of the genus Alpinia provide a variety of medicinal properties, such as, Alpinia zerumbet (Pers.) Burtt et Smith and A. purpurata (Vieill) K. Schum, which have a significant presence in Brazil. These species have been commercialized in the food and cosmetic industries. However, their greatest importance arises from the medicinal properties of their essential oils containing flavonoids, terpenoids and kavalactones which have been used in folk medicine to treat, for example, arterial hypertension and inflammatory processes. In addition, such species are also used in multidisciplinary studies, including phytochemistry, ethnobotany and biology, indicating the key pharmacological role of this genus in everyday life. Therefore, this work aims to present a bibliographic review of the genus Alpinia and its significance in therapeutic applications.
... In addition, this extract at doses up to 0.073 mg/mL had no effect on lipid peroxidation (Manosroi et al., 2005). Chloroform extract from P. campechiana fruits presented antioxidative and antinitrosative activities by employing two cellular experimental systems: phorbol ester-induced O 2 -generation from differentiated HL-60 human promyelocytic leukemia cells; and lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages (Murakami et al., 2005). The ethyl acetate extract presented anti-mitotic activity ex vivo (Hernandez et al., 2008). ...
O gênero Pouteria pertence à família Sapotaceae e pode ser encontrado em muitos continentes. As plantas desse gênero têm sido utilizadas na construção civil, na alimentação e também na medicina popular. Algumas atividades biológicas são reportadas às espécies desse gênero, tais como, antioxidante, anti-infamatória, antibacteriana e antifúngica, mas seu real potencial como fonte de novos fármacos ainda é pouco conhecido. Assim, uma revisão sobre a composição química e as atividades biológicas de Pouteria é apresentada, com o intuito de estimular a continuação dos estudos das espécies aqui citadas, e a investigação de outras espécies para as quais não foram encontrados relatos. _______________________________________________________________________________ ABSTRACT The genus Pouteria belongs to the family Sapotaceae and can be widely found around the World. These plants have been used as building material, as food, because the eatable fruits, as well as remedies in folk medicine. Some biological activities have been reported to species of this genus such as antioxidant, anti-infammatory, antibacterial and antifungal. However, the real potential of this genus as source of new drugs or phytomedicines remains unknown. Therefore, a review of the so far known chemical composition and biological activities of this genus is presented to stimulate new studies about the species already reported moreover that species have no reference about chemistry or biological activities could be found until now.
... Several health benefits relevant to IBD patients have been demonstrated for fruits with high antioxidant activity such as kiwifruit, including protection against carcinogenesis [29], improved iron status [30], enhanced adaptive immune response [31][32][33] and improved laxity [34,35]. In particular, extracts of both gold and green kiwifruit have demonstrated anti-inflammatory effects against macrophages stimulated with bacterial antigens to activate tolllike receptor signalling, reducing the secretion of pro-inflammatory mediators such as nitric oxide (NO), interleukin 1b, interleukin 12 (IL12), and tumour necrosis factor a (TNFa) [36][37][38]28]. ...
... In other countries around the Mediterranean sea, Iran, Afghanistan, India, China, and Japan, plants such as pomegranate (Punica granatum, Punicaceae), bitter gourds (Momocardia charantia), and other cucurbitacae, which contain high amounts of punicic acid a ClnA isomer (9Z,11E,13Z) containing cis-9, trans-11, cis-13 double bonds in the C18 carbon chain, are regularly consumed [34,35]. One might speculate that intake of these specific conjugated fatty acids could account for the lower incidence of inflammatory diseases in these populations [40,41]. The aims of this study were to investigate the effects of punicic acid on TNFa-induced ROS over-production by human neutrophils and to evaluate the effect of punicic acid in a rat model of 2, 4, 6- trinitrobenzenesulfonic acid (TNBS)-induced colitis. ...
Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo.
We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation.
These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.
... were purified as described earlier [28]. Briefly, Curcuma longa L. was extracted with chloroform and the chloroform layer was subjected silica gel column chromatography. ...
Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs of curcumin (Cur), such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin was investigated. The results indicate that the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-kappaB) activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-kappaB activation. The suppression of NF-kappaB activity correlated with inhibition of NF-kappaB reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC and BDMC was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-kappaB or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.
Adherence to the Mediterranean diet has been shown to lower the risk of developing chronic non-communicable diseases like cardiovascular and neurodegenerative diseases and cancer. Improvements in depression, participation in daily activities in older individuals, weight loss and a reduction in adverse pregnancy outcomes are associated with adherence to the Mediterranean diet. The number of studies that have evaluated barriers to adherence to the Mediterranean diet in the US and, in particular, in racial and ethnic minority populations within the US are few. Among Native American and Alaskan Native populations, studies evaluating traditional or alternative Mediterranean diet adherence for chronic non-infectious diseases is unavailable. Mediterranean diet scoring instruments used in studies in European and Mediterranean countries and among white participants in the US fail to capture the dietary patterns of racial and ethnic minority populations. In this narrative review, the food components of the traditional Mediterranean diet are discussed, adherence to the Mediterranean diet is examined in Mediterranean and non-Mediterranean countries and barriers preventing adherence to the Mediterranean diet in the US and among racial and ethnic minority populations is reviewed. Recommendations for improving nutrition education and intervention and for increasing adherence and cultural adaptions to the Mediterranean diet are provided.
Hypoxic conditions in the body have been reported to occur in aging and exercising muscles. It has been suggested that a reduction in ATP, due to hypoxia, may contribute to related declines in muscle performance. In this study, we established hypoxic assay systems and evaluated the effects of 65 phytochemicals on intracellular ATP content in C2C12 myotubes, to more accurately determine their physiological activities. We found intracellular ATP content in C2C12 myotubes to be reduced, under hypoxic conditions. However, kaempferol markedly increased it in this assay systems, by activating oxidative metabolism. The level of kaempferol in crops cultivated in highland areas or an artificial hypoxic environment, was significantly increased, while that of quercetin was either unchanged or significantly decreased. These results suggest crops may biosynthesize kaempferol to adapt to hypoxic environments, and that highland residents may benefit from eating such crops, with adaptive consequences.
Japan is an exceptionally healthy East Asian country with extended longevity. In addition, the typical levels of several proinflammatory proteins, including both C-reactive protein (CRP) and interleukin-6 (IL-6), are often reported to be low when compared to American and European populations. This analysis determined if blood levels of CRP and IL-6 were associated with 4 cultural practices reflective of Japanese behavior and customs -- drinking tea, eating seafood, consuming vegetables, and partaking in relaxing baths regularly – among 382 adults living in Tokyo. Regression models controlled for demographic factors, adiposity (BMI), physical exercise, smoking, alcohol use, and chronic illness (e.g., diabetes). Consuming a Japanese diet was associated with significantly lower CRP and IL-6 levels. More frequent bathing was associated with lower IL-6, but not specifically predictive of low CRP. This study has confirmed prior evidence for low inflammatory activity in Japanese adults and its association with several behavioral practices common in Japan.
Eicosanoids, the oxygenated metabolites formed from the polyunsaturated fatty acids (PUFAs) such as AA via the COX, LOX and EPOX pathways, are biologically active oxylipids regulating various physiological processes. Chronic inflammation may lead to cancer development by overexpression of pro-inflammatory mediators, oncogenes, COX-2 and 5-LOX, which regulate cell transformation into tumour cell and its proliferation, survival, metastasis, invasion, chemoresistance and radio resistance. Berberine exhibited anti-cancer and anti-inflammatory effects by blocking multiple pathways, including the COX-2 pathway. Chebulagic acid, a natural antioxidant from T. chebula, acts as a potent suppressor of lipopolysaccharide (LPS)-induced inflammation in mouse macrophages. Ellagic acid, present in certain fruits, nuts and vegetables, has been reported to possess anti-cancer and anti-inflammatory activities. Natural products have been found to be very effective in the elimination of side effects associated with inhibitors of enzymes of eicosanoids with more biocompatibility and with lesser side effects.
Introduction Chemical Overview of Resveratrol Sources of Resveratrol Epidemiologic Observations of Resveratrol Metabolism of Resveratrol Interaction of Resveratrol with Dietary Constituents Target Enzymes of Resveratrol Action Structure-Activity Relations of Resveratrol Pharmacological Preconditioning Effects of Resveratrol Antioxidant Power of Resveratrol Anti-Inflammation with Resveratrol Diabetes Cure with Resveratrol Cancer Cure with Resveratrol Antiaging Effects of Resveratrol Antiulcer Effects of Resveratrol Antiobese Effects of Resveratrol Other Health Benefits of Resveratrol Acknowledgment References
BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life. CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan. SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.” KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator.
Detailed investigations of the contents of antioxidant substances, such as carotenoids and polyphenols, in traditional Okinawan vegetables have not been conducted. In this study, we determined a- and b-carotene, lutein, chlorophyll, and polyphenol contents in traditional Okinawan vegetables. We compared several simultaneous extraction methods for carotenoids, chlorophylls, and polyphenols from vegetables, and concluded that the accelerated solvent extraction (ASE) system using 80% ethanol solution is the best method for the extraction of such compounds. The extract obtained by ASE was analyzed for carotenoids and chlorophylls using HPLC and for polyphenols using the Folin-Ciocalteu method. Among the vegetables that we analyzed, Nishiyomogi, Botanbouhuu, Hosobawadan, and Suizenjina revealed high b-carotene content. Moreover, Botanbouhuu was not only rich in β-carotene (5029 ± 629μg/100 g fresh weight), but also lutein (8.2 ± 1.3 mg/100 g fresh weight), total polyphenols (251.3 ± 23.4 mg/100 g fresh weight), and vitamin C (45.8 ± 15.4μg/100 g fresh weight). Thus, the present study revealed that Botanbouhuu is richer in various antioxidant substances than the other analyzed vegetables.
The traditional diet in Okinawa is anchored by root vegetables (principally sweet potatoes), green and yellow vegetables, soybean-based foods, and medicinal plants. Marine foods, lean meats, fruit, medicinal garnishes and spices, tea, alcohol are also moderately consumed. Many characteristics of the traditional Okinawan diet are shared with other healthy dietary patterns, including the traditional Mediterranean diet, DASH diet, and Portfolio diet. All these dietary patterns are associated with reduced risk for cardiovascular disease, among other age-associated diseases. Overall, the important shared features of these healthy dietary patterns include: high intake of unrefined carbohydrates, moderate protein intake with emphasis on vegetables/legumes, fish, and lean meats as sources, and a healthy fat profile (higher in mono/polyunsaturated fats, lower in saturated fat; rich in omega-3). The healthy fat intake is likely one mechanism for reducing inflammation, optimizing cholesterol, and other risk factors. Additionally, the lower caloric density of plant-rich diets results in lower caloric intake with concomitant high intake of phytonutrients and antioxidants. Other shared features include low glycemic load, less inflammation and oxidative stress, and potential modulation of aging-related biological pathways. This may reduce risk for chronic age-associated diseases and promote healthy aging and longevity.
Background:
The objective of this study was to investigate antioxidant and anti-inflammatory activity of cabbage phytochemicals.
Materials and methods:
Color coordinates were evaluated by colorimetry, and the antioxidant and anti-inflammatory activities were analyzed by spectrophotometer for some common cabbage varieties.
Results:
Red heads had the highest total antioxidant contents followed by Savoy, Chinese and green heads. The Chinese variety had the highest ABTS (2,2-azino-di-(3-ethylbenzthiazoline-sulfonic acid) antioxidant activity, was 5.72 μmol TE/g fw (Trolox equivalent). The green variety had the highest DPPH (free radical scavenging activity) antioxidant activity, which was 91.2 μmol TE/g fw. The red variety had the highest FRAP (ferric reducing antioxidant power) antioxidant activity, which was 80.8 μmol TE/g fw. The total phenol amounts were 17.2-32.6 mM trolox equivalent antioxidant capacity (TEAC) and the total flavonoid amounts were 40.0-74.2 mg quercetin per gram. Methanolic extracts of different cabbage heads showed different anti-inflammatory activity values. Chinese, Savoy and green heads had the highest anti-inflammatory activity, while red heads had the lowest.
Conclusions:
The results suggest that these varieties of cabbage heads could contribute as sources of important antioxidant and anti-inflammatory related to the prevention of chronic diseases associated to oxidative stress, such as in cancer and coronary artery disease.
To examine the role of two nutritional factors implicated in the healthy aging of the Okinawans: caloric restriction; and traditional foods with potential caloric restriction-mimetic properties.
Caloric restriction is a research priority for the US National Institute on Aging. However, little is known regarding health effects in humans. Some caloric restriction-related outcomes, such as cause-specific mortality and lifespan, are not practical for human clinical trials. Therefore, epidemiological data on older Okinawans, who experienced a caloric restriction-like diet for close to half their lives, are of special interest. The nutritional data support mild caloric restriction (10-15%) and high consumption of foods that may mimic the biological effects of caloric restriction, including sweet potatoes, marine-based carotenoid-rich foods, and turmeric. Phenotypic evidence is consistent with caloric restriction (including short stature, low body weight, and lean BMI), less age-related chronic disease (including cardiovascular diseases, cancer, and dementia), and longer lifespan (mean and maximum).
Both caloric restriction and traditional Okinawan functional foods with caloric restriction-mimetic properties likely had roles in the extended healthspan and lifespan of the Okinawans. More research is needed on health consequences of caloric restriction and foods with caloric restriction-mimetic properties to identify possible nutritional interventions for healthy aging.
The exceptional longevity of the Okinawa population may result from a combination of favorable factors and not only genetic determinants. The association of a protected environment with a way of life which combines specific food habits, low energy intake, physical activities, stress reduction, good familial support and rich social relations could explain this exception despite the low income in this population. Most of these factors are highly correlated with the culture and linked to the traditional lifestyle in Okinawa which may concentrate extremely favorable elements for health and longevity.
Inflammatory bowel disease (IBD) is a collective term for conditions characterised by chronic inflammation of the gastrointestinal tract involving an inappropriate immune response to commensal micro-organisms in a genetically susceptible host. Previously, aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (A. deliciosa) have demonstrated anti-inflammatory activity using in vitro models of IBD. The present study examined whether these kiwifruit extracts (KFE) had immune-modulating effects in vivo against inflammatory processes that are known to be increased in patients with IBD. KFE were used as a dietary intervention in IL-10-gene-deficient (Il10
− / −) mice (an in vivo model of IBD) and the C57BL/6J background strain in a 3 × 2 factorial design. While all Il10
− / − mice developed significant colonic inflammation compared with C57BL/6J mice, this was not affected by the inclusion of KFE in the diet. These findings are in direct contrast to our previous study where KFE reduced inflammatory signalling in primary cells isolated from Il10
− / − and C57BL/6J mice. Whole-genome gene and protein expression level profiling indicated that KFE influenced immune signalling pathways and metabolic processes within the colonic tissue; however, the effects were subtle. In particular, expression levels across gene sets related to adaptive immune pathways were significantly reduced using three of the four KFE in C57BL/6J mice. The present study highlights the importance of investigating food components identified by cell-based assays with appropriate in vivo models before making dietary recommendations, as a food that looks promising in vitro may not be effective in vivo.
The aim of this study was to evaluate the immunomodulatory effects of sugar cane extract (SCE) on the biological activities of neutrophils in mice. Six-week-old BALB/c mice were fed 1250 mg/kg of SCE once. The generation, migration and biological functions of neutrophils and the survival rates of the mice in response to Salmonella typhimurium infection were evaluated. The results show that the numbers of both bone marrow cells and neutrophils were significantly increased in response to SCE administration (p < 0.05) compared with controls. The migration, phagocytosis and H₂O₂ generation of neutrophils were all significantly enhanced in SCE-treated mice (p < 0.05). After challenge with S. typhimurium (lethal dose, 50% (LD₅₀), SCE-treated mice had a 19.2% higher survival rate and milder hepatic lesions than the controls. Additionally, fewer invasive bacteria were recovered from the spleens of SCE-treated mice. In conclusion, our results suggest that SCE has a positive regulatory effect on the biological function of mouse neutrophils that may increase host resistance against bacterial infections.
Several recent studies have shown the protective effects of resveratrol in various experimental conditions and pathological animal models. Clinical studies also indicate the beneficial effects of resveratrol in different human diseases. Resveratrol produces a cascade against of events from the initial death-provoking signal, DNA fragmentation, and cell death. Researchers recognized the beneficial effect of resveratrol, as an important component, of the overall injury that occurs in various disorders such as oxidative stress, myocardial injury, anticancer activity, antidiabetic activity, and antihypercholesterolemic effects. Many mechanisms have been proposed for the initiation of protective effects of resveratrol in various pathological events, and considerable evidence exists to indicate that many mediators are involved in the resveratrol-induced protection. The present review focuses on the history, and the beneficial effects and mechanisms of resveratrol in oxidative stress, myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic activities, and discusses those therapeutic tools, which warrant becoming clinically important.
Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage scavenger receptors (SRs), such as lectin-like ox-LDL receptor-1 (LOX-1), is a key event in atherosclerosis. In the present study, we used differentiated Caco-2 cells as a model of the human small intestine to evaluate the suppressive effects of 16 traditional food items selected from Okinawa on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced LOX-1 mRNA expression in THP-1 human monocyte-like cells. Three Zingiberaceae plants, Curcuma aromatica Salisbury, Curcuma longa L., and Zingiber zerumbet Smith, markedly suppressed that expression. When added to the apical sides of Caco-2 monolayers, zerumbone, a sesquiterpene from Z. zerumbet Smith, was found to permeate into the basolateral medium as an intact structure in a time-dependent manner. alpha-Humulene, a structural analog of zerumbone lacking the alpha,beta-unsaturated carbonyl group, did not suppress LOX-1 mRNA expression, indicating that its electrophilic moiety might play pivotal roles in its activities. Further, zerumbone attenuated the expression of SR-A, SR-PSOX, and CD36, but not that of CD68 or CLA-1, leading to a blockade of DiI-acLDL uptake, while it also inhibited the transcriptional activities of activator protein-1 and nuclear factor-kappaB. Together, our results indicate that zerumbone is a potential phytochemical for regulating atherosclerosis with reasonable action mechanisms.
Procedures are described for isolating turmerones from Curcuma longa rhizomes and for chromatographically separating α- from β-turmerone. Using a combination of spectroscopic techniques (especially high field 1H NMR spectroscopy and chiroptical methods) these compounds are shown to be (1′R, 6S)-2-methyl-6-(4-methylcyclohexa-2,4-dienyl)hept-2-en-4-one 2(α-turmerone) and (1′R, 6S)-2-methyl-6-(4-methylenecyclohex-2-enyl)hept-2-en-4-one 3(β-turmerone).
A housekeeping basolateral Cl- channel of rabbit gastric parietal cells, the single channel conductance of which is about 0.3 picosiemens, is opened by prostaglandin E2 and closed by intracellular application of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). In the present patch clamp study, we found a novel GTP gamma S-dependent regulatory mechanism of the Cl- channel. GTP gamma S significantly decreased the open probability of the single Cl- channel without altering unit conductance. An intracellular application of superoxide dismutase (SOD; 100 units/ml) inhibited the GTP gamma S (50 microM)-induced closure of the Cl- channel. SOD plus catalase (100 units/ml) also inhibited the GTP gamma S-induced effect, while catalase alone did not inhibit it. In the absence of GTP gamma S, an intracellular application of hydrogen peroxide (H2O2; 30 microM) did not affect the Cl- channel current. Desferrioxamine (50 microM) which inhibits hydroxyl radical (.OH) production was without effect on the GTP gamma S-induced closure. These results suggest that the GTP gamma S-induced closure of the Cl- channel was due to intracellular production of superoxide (O2.-), but not due to .OH or H2O2. Furthermore, an artificial production of O2.- inside the cell by lumazine (50-100 microM) plus xanthine oxidase (0.5-1 milliunit/ml) in the absence of GTP gamma S also closed the channel. The lumazine/xanthine oxidase-induced closure of the channel was inhibited by SOD, but not by catalase or desferrioxamine. We conclude from these results that GTP-binding protein-coupled production of O2.- leads to closure of the Cl- channel in rabbit gastric parietal cells.
Although nitric oxide (NO) is an important biological mediator, excessive production in inflammation is thought to be a causative factor of cellular injury and cancer in the long term. In the present study the effects of 1'-acetoxychavicol acetate (ACA), which has anticarcinogenic properties, on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide or interferon-gamma were examined. ACA suppressed NO production dose dependently with an IC50 of 160 ng/ml (680 nM). The decrease in NO production was shown to parallel reduced expression of iNOS mRNA and protein. The influence of ACA on transcription factors, such as NF-kappaB, AP-1 and Stat1, which are involved in expression of the iNOS gene was assessed. ACA was found to suppress degradation of IkappaB, an NF-kappaB inhibitory factor, and consequently inhibit NF-kappaB activation. Activation of AP-1 and Stat1 was also blocked by ACA treatment. Thus we demonstrate that ACA exerts potent inhibitory effects on NO production, apparently mediated by modulation of activation of several transcription factors. This could contribute to the anticarcinogenic properties of ACA.
A facile stereoselective synthetic route to (7S,9R)-(+)-bisacumol 1 has been achieved. This novel approach derives its asymmetry by employing asymmetric dihydroxylation and CBS reduction processes. The resulting sesquiterpene 1 was produced with highly enantio- and diastereoselectivity.
While the design of molecules that inhibit or antagonize the functions of specific macromolecules is now well precedented, in many cases the structural information requisite to the design process is lacking. The tools of molecular biology can now furnish the target macromolecules for use in mechanism-based exploration; highly defined assays can be devised based upon the known biochemistry of these macromolecules to permit the discovery of novel inhibitors or antagonists present in chemical collections. Presently, we describe a set of assays directed toward the discovery of novel inhibitors of eukaryotic topoisomerase I, an enzyme critical to maintenance of chromosomal DNA topology and therefore essential for normal replication and transcription. The identification of chebulagic acid as an extraordinarily potent and mechanically novel inhibitor of topoisomerase I illustrates the potential of this approach.
Asbestos exposure causes diffuse interstitial pulmonary fibrosis. Since alveolar epithelial cell injury is hypothesized to precede the fibrotic response in asbestosis, we investigated whether asbestos, either alone or in conjunction with neutrophils (PMNs), injured cultured human pulmonary epithelial cells (HPECs). HPEC cytotoxicity was assessed with a standard 51chromium release assay after a 16-hour incubation with asbestos and PMNs. Negligible HPEC cytotoxicity was observed after incubation with either amosite asbestos (500 micrograms/ml) or PMNs alone in serum-free media. However, incubation with both asbestos and PMNs caused significant HPEC injury, which was asbestos dose-dependent; causing 25% +/- 4% detachment and 52% +/- 8% 51chromium release with 500 micrograms/ml asbestos. The cytotoxic effects of asbestos plus PMNs were nearly completely attenuated with serum (20%) or catalase (100 micrograms/ml) but were not prevented with scavengers of superoxide anion, hydroxyl radical, or hypochlorous acid. A role for hydrogen peroxide (H2O2) in mediating HPEC injury was also suggested by the demonstration of asbestos-induced generation of H2O2 by PMNs. Furthermore, H2O2 alone (10(-4)mol/L) caused significant HPEC damage. Intimate contact between asbestos-activated PMNs and HPECs was a necessary requirement for PMN-mediated HPEC cytotoxicity. These data suggest that pulmonary epithelial cell injury is mediated in part by H2O2 release from asbestos-activated PMNs as well as intimate contact between the epithelial cell, PMNs, and asbestos.
Evidence has been obtained that implicates the generation of reactive oxygen species as an early and critical event in the promotion of neoplastic transformation in mouse JB6 cells. The time courses for specific inhibition by CuZn-superoxide dismutase (CuZn-SOD) of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of neoplastic transformation in JB6 cells and for changes in antioxidant enzyme activities associated with TPA-exposure were examined. The antipromoting effect of CuZn-SOD was found to be critically dependent on the time of addition of CuZn-SOD relative to the start of a 14-day exposure of cells to TPA. Treatment of JB6 P+ Clone 22 and Clone 41 cells with CuZn-SOD for 18 h before, simultaneously with or up to 1 h after exposure to TPA, all inhibited promotion of transformation maximally. Delay of addition of CuZn-SOD by 2 h or more after the start of TPA treatment resulted in a marked decrease in the promotion inhibitory effect. CuZn-SOD added 24 or 48 h after TPA had no effect on promotion of transformation. Exposure of JB6 cells to 0.2- (superoxide anion radical) generated exogenously by the aerobic xanthine oxidase reaction resulted in promotion of neoplastic transformation that was prevented by concurrent addition of CuZn-SOD. Taken together these studies provide evidence that increased superoxide anion generation within the first 2 h following TPA exposure is an essential event in promotion of transformation in JB6 cells. Upon TPA exposure, JB6 Clone 41 cells exhibited time-specific activity changes in the cellular SOD, glutathione peroxidase (GSH-Px), and catalase. SOD and GSH-Px activities were reduced to 54% and 26% respectively of basal levels within 2 h of TPA treatment. GSH-Px activity recovered to basal levels within 4 h and CuZn-SOD within 48 h. Catalase activity was maximally reduced to 50% of basal within 1 h after TPA treatment and rebounded to greater than basal levels within 4 h. It is postulated that a c-kinase-dependent event induces rapid elevation of superoxide anion following TPA exposure and that this leads to reduced activity of antioxidant enzymes. Since antipromotion by exogenous CuZn-SOD is effective only during the first 2 h following TPA exposure, this suggests that the promotion-relevant 0.2- elevation is transient.
One hundred twenty-one species of edible plants (133 test-parts) were screened against possible anti-tumor promoting activity by an in vitro short-term assay system of inhibition of Epstein-Barr virus (EBV) activation induced by a phorbol-ester promoter, 12-O-hexadecanoylphorbol-13-acetate (HPA). The methanol-extracts (ME) of 14 species of the edible plants strongly inhibited the activation, 7 moderately and 12 weakly inhibited it. On partition of the randomly selected inactive ME (26 species) with ethyl acetate and water, 13 and 2 species were active, more or less, in the ethyl acetate and water soluble part, respectively. Thus, this result suggested that anti-tumor promoters occur in a wide variety of edible plants. The anti-tumor promoting activity in the crude extracts may be enhanced or reduced with co-occurring factors acting additively, synergistically or antagonistically.
Oxidants, such as those generated by metabolically activated phagocytes in inflammation, have been implicated in the metabolic activation of carcinogens, and in this study we demonstrate that the interaction of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) with phorbol ester-stimulated polymorphonuclear leukocytes (PMNs) results in the generation of both a chemiluminescent intermediate and one that covalently binds to DNA. Cu(II)(3,5-diisopropylsalicylic acid)2 (CuDIPS), a biomimetic superoxide dismutase, and azide, a myeloperoxidase inhibitor, inhibited both of these reactions, indicating a dependency on oxygen-derived oxidants in these hydrocarbon-activation processes. Concordant with the formation of a carcinogen-DNA adduct, the admixture of BP 7,8-dihydrodiol and phorbol ester-stimulated PMNs elicited mutagenesis in Salmonella typhimurium strain TA100. 7,8-Dihydro-BP and BP cis-7,8-dihydrodiol were also mutagenic, whereas derivatives lacking a double bond at the 9,10 position were not. These results demonstrate that oxidants generated by metabolically stimulated PMNs can activate penultimate polycyclic aromatic hydrocarbons to a genotoxic metabolite and further defines a role for inflammation in carcinogenesis.
The effect of phorbol ester tumour promoters on the release of superoxide anion radicals .O2- by human peripheral leukocytes and the role of such radicals in tumour promotion of mouse skin was studied. No significant difference was found between complete [12-O-tetradecanoylphorbol-13-acetate (TPA)] as compared with incomplete [12-O-retinoylphorbol-13-acetate (RPA), 12-O-(2Z,4E,6,8)tetradecatetraenoylphorbol-13-acetate (Ti8), mezerein] tumour promoters upon induction of .O2- when measured by the reduction of ferricytochrome c. The semisynthetic phorbol esters 12-O-ethacrynylphorbol-13-acetate (EPA) and 4-O-methyl-TPA were less active, and phorbol diacetate, phorbol and ionophore A 23187 were found to be inactive in stimulating superoxide anion radicals. TPA-induced .O2- release from leukocytes was strongly inhibited by Cu(II)-(diisopropylsalicylate)2 (CuDIPS), and, to a lesser extent, by ethacrynic acid, nordihydroguaiaretic acid and quercetin. Retinoic acid exhibited only a moderate inhibitory effect. No .O2- release was observed in epidermal cell cultures upon TPA treatment. When analysed by the alkaline elution technique, TPA-induced .O2- release from leukocytes did not lead to measurable DNA damage in co-cultivated keratinocytes even in the presence of DNA repair inhibitors. In multi-stage-tumourigenesis experiments including two-stage promotion, retinoic acid, ethacrynic acid and CuDIPS were unable to inhibit tumour promotion in mouse skin when applied in combination with TPA in first stage promotion. gamma-Irradiation at a dose level shown to cause DNA damage in vitro could not replace TPA as a stage I-promoting agent. It is concluded that superoxide anion radicals--if related to promotion at all--may play a role in stage II rather than in stage I of mouse skin tumour promotion.
A total of 135 methanol extracts from 48 plant families (107 species) of edible Indonesian plants were screened for their in vitro anti-tumor-promoting activities using the tumor promoter 12-O-hexadecanoylphorbol-13-acetate (HPA)induced Epstein-Barr virus (EBV) activation test in Raji cells. Examined at a concentration of 200 mg/ml, 71% of the extracts inhibited EBV activation by 30% or more. The rate is comparable to the rate observed in our previous tests of edible Thai (60%) plants and much higher than the rate (26%) observed with Japanese plants. In particular, the plant families Zingiberaceae (13/13 active) and Umbelliferae (7/8 active) are suggested to be desirable sources of effective cancer-preventive agents because of the strikingly high frequency of inhibitory activity. Thus, a high potential of edible Southeast Asian plants for cancer chemoprevention is indicated.
The influence of 1'-acetoxychavicol acetate (ACA) during the initiation stage was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamster tumorigenesis model. Ninety male 5-week-old hamsters were divided into three groups, each consisting of 30 animals, and s.c. injected with 20 mg / kg of BOP twice with a one-week interval. Groups 1 through 3 were fed diet supplemented with ACA at concentrations of 500, 100 and 0 ppm, respectively, for 3 weeks starting one week before the first carcinogen application. At the termination of experimental week 54, the total incidence and multiplicity of cholangiocellular adenomas and carcinomas in group 1 (17.9% and 0.3 < 0.9) were significantly (P < 0.05 and P < 0.01) decreased as compared to the group 3 values (50.0% and 0.7 < 0.8). The ACA treatments also showed a tendency to reduce the development of preneoplastic lesions in the pancreas, a main target organ of BOP, although this was not statistically significant. Our results thus indicate that ACA exerts an inhibitory effect on BOP-induced cholangiocarcinogenesis in hamsters. Taken together with previous findings of inhibited colon, oral and skin carcinogenesis in rats and mice, they suggest that ACA is a candidate chemopreventive agent with a wide spectrum of activity.
Epithelial xanthine oxidase (XOD) is one of the major enzymes responsible for superoxide (O(2)(-)) generation, which is involved in oxidative stress. However, there are few known reports of a convenient bioassay to detect cellular XOD activity. We tested several cell lines, and found that AS52, from Chinese hamster ovary cells, produced a significant level of O(2)(-) in response to 12-O-tetradecanoylphorbol 13-acetate (TPA), and this activity was markedly inhibited by allopurinol, an XOD inhibitor. Using AS52 cells and differentiated HL-60 cells, we conducted screening tests of edible Japanese plant extracts for their inhibitory activities toward TPA-induced O(2)(-) generation from both reduced nicotinamide adenine dinucleotide oxidase (HL-60) and XOD (AS52). Notably, the extracts from mioga ginger, rape, avocado, carrot, turnip, taro, and shimeji showed potent inhibition of O(2)(-) generation in both cell lines. These results suggest that several edible Japanese plants carry a significant antioxidative and cancer preventive potential.
Elucidation of the mechanisms underlying potential anticancer drugs continues and unraveling these mechanisms would not only provide a conceptual framework for drug design but also promote use of natural products for chemotherapy. To further evaluate the efficacy of the anticancer activity of 1'-acetoxychavicol acetate (ACA), this study investigates the underlying mechanisms by which ACA induces death of Ehrlich ascites tumor cells. ACA treatment induced loss of cell viability, and Western blotting analysis revealed that the compound stimulated tyrosine phosphorylation of several proteins with 27 and 70 kDa proteins being regulated in both dose- and time-dependent manner prior to loss of viability. Protein tyrosine kinase inhibitor herbimycin A moderately protected cells from ACA-induced toxicity. In addition, cellular glutathione and protein sulfydryl groups were also significantly reduced both dose- and time-dependently during evidence of cell death. Replenishing thiol levels by antioxidant, N-acetylcysteine (NAC), an excellent supplier of glutathione and precursor of glutathione, substantially recovered the viability loss, but the recovery being time-dependent, as late addition of NAC (at least 30 min after ACA addition to cultures) was, however, ineffective. Addition of NAC to ACA treated cultures also abolished tyrosine phosphorylation of the 27 kDa protein. These results, at least partly, identify cellular sulfhydryl groups and protein tyrosine phosphorylation as targets of ACA cytotoxicity in tumor cells.
Beta-turmerone and ar-turmerone, sesquiterpenoids isolated from the rhizome of Curcuma zedoaria, inhibited lipopolysaccharide (LPS)-induced prostaglandin E 2 production in cultured mouse macrophage cell RAW 264.7 in a dose-dependent manner (IC 50 = 7.3 microM for beta-turmerone; IC 50 = 24.0 microM for ar-turmerone). In addition, these compounds exhibited inhibitory effects on LPS-induced nitric oxide production in the cell system.
Chemoprevention with food phytochemicals is currently regarded as one of the most attractive strategies for cancer control. We have been continuously working on the identification and characterization of chemopreventive phytochemicals extracted from a diverse range of edible plants. Recently, we have utilized a convenient assay, the tumor promoter-induced superoxide generation test, with differentiated HL-60 cells for primary screening, and performed chemical studies of antioxidative food phytochemicals. Here, we report our criteria for evaluation of new types of chemopreventors on the basis of the involvement of leukocyte-derived reactive oxygen in carcinogenesis.