Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer

The normal biochemical reactions in our body, increased exposure to the environment, and higher levels of dietary xenobiotic's result in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS create oxidative stress in different pathophysiological conditions. The reported chemical evidence suggests that dietary antioxidants help in disease prevention. The antioxidant compounds react in one-electron reactions with free radicals in vivo/in vitro and prevent oxidative damage. Therefore, it is very important to understand the reaction mechanism of antioxidants with the free radicals. This review elaborates the mechanism of action of the natural antioxidant compounds and assays for the evaluation of their antioxidant activities. The reaction mechanisms of the antioxidant assays are briefly discussed (165 references). Practical applications: understanding the reaction mechanisms can help in evaluating the antioxidant activity of various antioxidant compounds as well as in the development of novel antioxidants.

https://pubs.rsc.org/en/content/articlepdf/2015/RA/C4RA13315C

Free radicals, natural antioxidants, and their reaction mechanisms

Chemistry of biologically important synthetic organoselenium compounds.

Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways. Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction. The role of other cells is at present not as well defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Mucosal inflammation in asthma.

http://www.jbc.org/content/259/5/3308.full.pdf

Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc.

Most studies on garlic during the past 15 years have been primarily in the fields of cardiovascular and cancer research. Cardiovascular studies have been mainly related to atherosclerosis, where effects were examined on serum cholesterol, LDL, HDL, and triglycerides. Although the studies were not consistent in relation to the dosage, standardization of garlic preparations, and period of treatment, most findings suggest that garlic decreases cholesterol and triglycerides levels in patients with increased levels of these lipids. Lowering of serum lipids by garlic ingestion may decrease the atherosclerosis process. The other major beneficial effect of garlic is due to its antithrombotic actions. This field of garlic research has been extensively studied. Garlic extracts and several garlic constituents demonstrate significant antithrombotic actions both in vitro and in vivo systems. Allicin and adenosine are the most potent antiplatelet constituents of garlic because of their in vitro effects. Since both allicin and adenosine are rapidly metabolized in human blood and other tissues, it is doubtful that these compounds contribute to any antithrombotic actions in the body. In addition, ajoene also seems not to be an active antiplatelet principle, because it is not naturally present in garlic, garlic powders, or other commercial garlic preparations. Only a small amount of ajoene can be found in garlic oil-macerates; however, ajoene is being developed as a drug for treatment of thromboembolic disorders. Recent findings on the identification of potent enzyme inhibiting activities of adenosine deaminase and cyclic AMP phosphodiesterase in garlic extracts are interesting, and may have a significant role in the pharmacological actions in the body. Presence of such enzyme inhibitors in garlic may perhaps explain several clinical effects in the body, including the antithrombotic, vasodilatory, and anticancer actions. Epidemiological studies have suggested that garlic plays a significant role in the reduction of deaths caused by malignant diseases. This had led many investigators to examine garlic and garlic constituents for their antitumor and cytotoxic actions both in vitro and in laboratory animals. The data from these investigations suggest that garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. In summary, the epidemiological, clinical, and laboratory data have proved that garlic contains many biologically and pharmacologically important compounds, which are beneficial to human health from cardiovascular, neoplastic, and several other diseases. Numerous studies are in progress all over the world to develop effective and odorless garlic preparations, as well as to isolate the active principles that may be therapeutically useful.

Therapeutic actions of garlic constituents

Publisher Summary This chapter describes the purification procedure of purine nucleoside phosphorylase (PNPase) enzyme from human erythrocytes PNPase is crystallized from human erythrocytes, where it is present in relatively high concentration (about 13 units/ml packed cells) PNPase is essential for the reutilization of purine ribo- and deoxyribonucleosides in these cells that lack the de novo pathway for nucleotide synthesis The enzyme is found deficient in erythrocytes and lymphocytes of individuals who also lack T-lymphocyte functions Hypoxanthine formed in the reaction is oxidized to uric acid by xanthine oxidase The protein concentration is determined from absorbancy at 280 nm during purification All steps are carried out at 0–5° Activation of enzymic activity is observed at high concentrations of nucleoside substrates After the electrophoretic fractionation of the enzyme, it is seen that activation is more pronounced in the acidic variants than in the basic variants The effect of pH on kinetic parameters suggests an essential role for cysteine and histidine in catalysis

[72] Purine nucleoside phosphorylase from human erythrocytes

Forskolin, a diterpene from the roots of an Indian plant, Coleus forskohlii, is a potent platelet aggregation inhibitor and has been examined for its effects on (a) tumor-induced human platelet aggregation and (b) pulmonary tumor colonization in mice. These studies employed a subline of B16 murine melanoma, B16-F10 (highly metastatic to lungs). Forskolin (2 microM) strongly inhibits the melanoma cell-induced human platelet aggregation. A single dose of forskolin (82 micrograms/mouse) administered intraperitoneally 30 or 60 min prior to tail vein injection of cultured B16-F10 cells (2 or 3 X 10(5) cells/mouse) reduced tumor colonization in the lungs by more than 70%. Similar results were obtained in three separate experiments. These findings raise the possibility that forskolin could prove of value in the clinic for the prevention of cancer metastasis.

Forskolin: A potential antimetastatic agent

Analogs of purine and pyrimidine nucleosides have received considerable attention in many laboratories concerned with the development of chemotherapeutic agents for malignancies, viruses, and tropical parasites. In addition, a number of these compounds have shown important immunosuppressive activity or have proved of use for the treatment of diseases such as psoriasis. For the past few years, this laboratory has been interested in the interaction of natural or analog purine nucleosides with the formed elements of human blood, i.e., erythrocytes, platelets and lymphocytes. Although these studies were designed originally to analyze the pathways of purine nucleoside metabolism in these cells, a number of unexpected observations have been made that have not only broadened our understanding of normal cellular functions but that also suggest possible useful applications. This report summarizes a number of investigations that have been published earlier or that will be published in greater detail in the future.

Kailash C. Agarwal

Papers

Therapeutic actions of garlic constituents

[72] Purine nucleoside phosphorylase from human erythrocytes

Forskolin: A potential antimetastatic agent

Incorporation of analog purine nucleosides into the formed elements of human blood: erythrocytes, platelets, and lymphocytes*

Identification and isolation on a large scale of guanylate kinase from human erythrocytes. Effects of monophosphate nucleotides of purine analogs.