In vitro studies on mangiferin protection against cadmium-induced human renal endothelial damage and cell death via the MAP kinase and NF-κB pathways.

The therapeutic effects of the natural antioxidant mangiferin (a xanthonoid and potent oxygen free radical scavenger), which is widely distributed in mango fruit, against CdCl(2)-induced toxicity in human renal glomerulus endothelial cells (HRGEC) were investigated. The viability of HREGCs that were treated with CdCl(2) (25 µ mol) and co-treated with mangiferin (75 µ mol) for 24 h was measured by crystal violet dye. The exposure of human glomerulus renal endothelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal proinflammatory cytokines known to play a significant role in renal inflammation. Proinflammatory cytokine secretion by human renal glomerulus endothelial cells could be the result of cadmium-induced IL-6 secretion via an NF-κB-dependent pathway. However, IL-8 secretion involves the phosphor-JNK phospho-p38 signaling pathway. The results of the current study reveal that mangiferin could prevent both cadmium-induced IL-6 and IL-8 secretion by human glomerulus endothelial cells and be used to prevent renal inflammation.

D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-kB

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague–Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-alfa (TNF-alfa), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the abovementioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis

D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.

Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets.

A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

Kaempferol, a potential cytostatic and cure for inflammatory disorders.

Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction, cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer.

Antioxidants and human diseases.

Oxidative stress plays a pivotal role in the development of human diseases. Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid, superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl radical are involved in growth, differentiation, progression and death of the cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and other small molecules. Low concentrations of ROS has an indispensable role in intracellular signalling and defence against pathogens, while, higher amounts of ROS play a role in number of human diseases, including arthritis, cancer, diabetes, atherosclerosis, ischemia, failures in immunity and endocrine functions. Antioxidants presumably act as safeguard against the accumulation of ROS and their elimination from the system. The aim of this review is to highlight advances in understanding of the ROS and also to summarize the detailed impact and involvement of antioxidants in selected human diseases.

D-pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-κB.

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.

Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice.

AIM OF THE STUDY: In the present study the effects of mangiferin were tested against lung cancer-bearing mice in both the pre-initiation and post-initiation periods. MATERIALS AND METHODS: Healthy male Swiss albino mice (6-8 weeks old) were used throughout the study. The animals were treated with mangiferin (100 mg/kg body weight dissolved in corn oil) two weeks before (pre-initiation) and the twelfth week after (post-initiation) the establishment of B (a) P (50 mg/kg body weight)-induced lung carcinoma. RESULTS: The body weight decreased and the lung weight and levels of xenobiotic and liver marker enzymes markedly increased in the carcinogen-administered animals; and mangiferin treatment brought the values of these parameters back to the near-normal ones. The activities of lysosomal enzymes in the animals with B (a) P-induced experimental lung carcinogenesis were also assessed. In these animals there was an increase in the activities of lysosomal enzymes such as acidphosphatase, ß-glucuronidase, N-acetyl glucosaminidase, and ß-galactosidase. CONCLUSION: Supplementation with mangiferin attenuated all these alterations, thus indicating its anticancer effect. Overall, the above data showed that the anticancer effect of mangiferin as a chemopreventive agent was pronounced.

Cancer preventive efficacy of marine carotenoid fucoxanthin: cell cycle arrest and apoptosis.

Epidemiological investigations have shown that overcoming the risk of cancer is related to the consumption of green vegetables and fruits. Many compounds from different origins, such as terrestrial plants and marine and microbial sources, have been reported to have therapeutic effects of which marine sources are the most important because the diversity of marine life is more varied than other sources. Fucoxanthin is one important compound with a marine origin and belongs to the group of carotenoids; it can be found in marine brown seaweeds, macroalgae, and diatoms, all of which have remarkable biological properties. Numerous studies have shown that fucoxanthin has considerable medicinal potential and promising applications in human health. In this review, we summarize the anticancer effects of fucoxanthin through several different mechanisms including anti-proliferation, induction of apoptosis, cell cycle arrest and anti-angiogenesis, and its possible role in the treatment of cancer.

The vascular endothelium and human diseases.

Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.

Immunomodulatory Effect of Mangiferin in Experimental Animals with Benzo(a)Pyrene-induced Lung Carcinogenesis.

The immunomodulatory activity of mangiferin was studied in various groups of animals. For this study, adult Swiss albino male mice were treated with benzo(a)pyrene, abbreviated as B(a)P, at 50 mg/kg body weight orally twice a week for 4 weeks; and mangiferin was also given orally (pre- and post-initiation of carcinoma) at 100 mg/kg body weight. Immunocompetence and immune complexes as measured by phagocyte index, avidity index, and soluble immune complex (SIC) levels (p<0.001), as well as NBT reduction, were decreased in the B(a)P-treated animals;whereas increased levels of immunocompetence were noted in the mangiferin-treated animals given B(a)P (p<0.001, p<0.05). The levels of immunoglobulins such as IgG and IgM were decreased considerably (p<0.001) in the B(a)P-treated animals compared with their levels in the control animals; whereas the IgA level was increased (p<0.001). In the mangiferin-treated experimental animals given B(a)P, the levels of IgG and IgM were significantly (p<0.001, p<0.05) increased whereas the IgA level was decreased compared with those for the B(a)P-treated mice. Oxidative changes in lymphocytes, neutrophils, and macrophages were also measured. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in the lymphocytes, polymorphonuclear cells (PMN), and macrophages from B(a)P-treated mice were significantly reduced and increased, respectively, by the mangiferin treatment. This study confirms the immunomodulatory effect of mangiferin and shows an immunoprotective role arbitrated through a reduction in the reactive intermediate-induced oxidative stress in lymphocytes, neutrophils, and macrophages.

Beneficial effects of green tea: a literature review.

The health benefits of green tea for a wide variety of ailments, including different types of cancer, heart disease, and liver disease, were reported. Many of these beneficial effects of green tea are related to its catechin, particularly (-)-epigallocatechin-3-gallate, content. There is evidence from in vitro and animal studies on the underlying mechanisms of green tea catechins and their biological actions. There are also human studies on using green tea catechins to treat metabolic syndrome, such as obesity, type II diabetes, and cardiovascular risk factors.Long-term consumption of tea catechins could be beneficial against high-fat diet-induced obesity and type II diabetes and could reduce the risk of coronary disease. Further research that conforms to international standards should be performed to monitor the pharmacological and clinical effects of green tea and to elucidate its mechanisms of action.

Effect of fresh apple extract on glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells in vitro.

Consumption of fruits and vegetables has been associated with a low incidence of cardiovascular and other chronic diseases. The present study was aimed at evaluating the protective effects of fresh apple extract (AE) on human umbilical vein endothelial cells (HUVEC) exposed to cytotoxic glycated protein (GFBS)/iron (FeCl(3)) chelate. The experimental design comprised 10 groups with 5 flasks in each group. Group I was treated with 15% foetal bovine serum (FBS). Groups II, III and IV were treated with GFBS (70 microM), FBS + FeCl(3) (20 microM), and GFBS + FeCl(3), respectively. The other six groups were as follows: Group V, GFBS + AE (100 microg); Group VI, FBS + FeCl(3) + AE (100 microg); Group VII, GFBS + FeCl(3) + AE (100 microg); Group VIII, GFBS + AE (250 microg); Group IX, FBS + FeCl(3) + AE (250 microg); and Group X, GFBS + FeCl(3) + AE (250 microg). After 24 h incubation, cells were collected from all the experimental groups and assessed for lipid peroxidation (LPO) and activities of the antioxidant enzymes cytochrome c reductase and glutathione S-transferase (GST). HUVEC incubated with glycated protein (GFBS) either alone or combined with iron chelate showed a significant (p < 0.001) elevation of LPO accompanied by depletion of superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to increased microsomal cytochrome c reductase and decreased GST activities. Treatment of GFBS- or GFBS + FeCl(3)-exposed HUVEC with AE at 100 or 250 microg significantly decreased the level of LPO and returned the levels of antioxidants cytochrome c reductase and GST to near normal in a dose-dependent manner. The extracts recovered viability of HUVEC damaged by GFBS-iron treatment in a concentration-dependent manner. These findings suggest a protective effect of AE on HUVEC against glycated protein/iron chelate-induced toxicity, which suggests that AE could exert a beneficial effect by preventing diabetic angiopathies.

Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells.

Astaxanthin (ASX), a red carotenoid pigment with no pro-vitamin A activity, is a biological antioxidant that occurs naturally in a wide variety of plants, algae and seafoods. This study investigated whether ASX could inhibit glycated protein/iron chelate-induced toxicity in human umbilical-vein endothelial cells (HUVEC) by interfering with ROS generation in these cells. Glycated fetal bovine serum (GFBS) was prepared by incubating fetal bovine serum (FBS) with high-concentration glucose. Stimulation of cultured HUVECs with 50 mm 1 mL of GFBS significantly enhanced lipid peroxidation and decreased antioxidant enzyme activities and levels of phase II enzymes. However, preincubation of the cultures with ASX resulted in a marked decrease in the level of lipid peroxide (LPO) and an increase in the levels of antioxidant enzymes in an ASX concentration-dependent manner. These results demonstrate that ASX could inhibit LPO formation and enhance the antioxidant enzyme status in GFBS/iron chelate-exposed endothelial cells by suppressing ROS generation, thereby limiting the effects of the AGE-RAGE interaction. The results indicate that ASX could have a beneficial role against glycated protein/iron chelate-induced toxicity by preventing lipid and protein oxidation and increasing the activity of antioxidant enzymes.

Protective effect of different parts of Cassia fistula on human umbilical vein endothelial cells against glycated protein-induced toxicity in vitro.

The protective effect of methanol extracts of Cassia fistula (flowers, leaves and bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC) against toxicity induced by glycated protein (GFBS) in vitro. The experiments consisted of eight groups of HUVEC with five flasks in each group. Group I was treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six groups were treated with GFBS plus 25 and 50 microg of each of the three types of C. fistula extracts. After 72 h of incubation, cells were collected and tested for lipid peroxidation, antioxidant enzyme activities and glutathione S-transferase (GST). The protective effect of C. fistula extracts against GFBS-induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT assays. Results showed that HUVEC incubated with GFBS alone showed a significant (P < 0.001) elevation of lipid peroxidation accompanied by depletion of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of HUVEC with C. fistula extracts at a concentration of 25 and 50 microg significantly decreased lipid peroxidation and normalized the activities of the antioxidant enzymes and GST levels in a concentration-dependent manner. Morphological changes of HUVEC were compared with respective controls; in addition, the C. fistula extracts increased the viability of HUVEC damaged by GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced toxicity suggested a potential beneficial effect of the extract in preventing diabetic angiopathies.