Harpal S. Buttar

Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention

Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked.

Bovine colostrum: an emerging nutraceutical

Abstract Nutraceutical, a term combining the words “nutrition” and “pharmaceuticals”, is a food or food product that provides health benefits as an adjuvant or alternative therapy, including the treatment and prevention of infectious diseases in children and adults. There is emerging evidence that bovine colostrum (BC) may be one of the promising nutraceuticals which can prevent or mitigate various diseases in newborns and adults. Immunity-related disorders are one of the leading causes of mortality in the world. BC is rich in immunity, growth and antimicrobial factors, which promote tissue growth and the maturation of digestive tract and immune function in neonatal animals and humans. The immunoglobulins and lactoferrin present in colostrum are known to build natural immunity in newborns which helps to reduce the mortality rate in this population. Also, the side-effect profile of colostrum proteins and possible lactose intolerance is relatively less in comparison with milk. In general, BC is considered safe and well tolerated. Since colostrum has several important nutritional constituents, well-designed, double-blind, placebo-controlled studies with colostrum products should be conducted to widen its therapeutic use. The objectives of this review are to create awareness about the nutraceutical properties of colostrum and to discuss the various ongoing alternative treatments of colostrum and its active ingredients as well as to address colostrum’s future nutraceutical and therapeutic implications in humans.

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

&NA; A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non‐communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up‐to‐date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration. Graphical abstract: Figure. No caption available.

Evaluation of the antioxidant properties of tryptophan and its metabolites in in vitro assay.

Abstract Background: Human milk contains a number of nutrients and bioactive ingredients which play an important role in the growth and development of infants. One important nutrient and bioactive ingredient of human milk is L-tryptophan. L-Tryptophan is an essential aromatic α-amino acid and is required in the diet of children and adult humans. As an essential amino acid, it is needed for protein synthesis and as a precursor of key biomolecules such as serotonin, melatonin, tryptamine, niacin, quinolinic acid and kynurenic acid, nicotinamide adenine dinucleotide. The aim of the study was to evaluate the antioxidant, anti-inflammatory and antiproliferative properties of tryptophan isolated from enzymatic hydrolysates from human milk and its metabolites on human glioma U251 cells and to evaluate the effects of human recombinant (hrIFNγ) on molecular ions of tryptophan and its metabolites in human glial U251 cells. Methods: The cytotoxicity was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The antioxidant property was assessed by the oxygen radical scavenging capacity (ORAC) method. The anti-inflammatory effect was determined by the enzyme-linked immunosorbent assay (ELISA) against cytokines IL-6 and TNF-α. The effects of recombinant human (rhIFNγ) on molecular ions of tryptophan and its catabolites were evaluated by mass spectrometry. The tryptophan was isolated from milk peptides following enzymatic digestion, followed by separation by chromatographic and mass spectrometric methods. Results: Tryptophan from human milk exhibited profoundly higher oxygen radical absorption capacity (7,986±468 µm Trolox equivalent (TE)/g) than that of whole human milk (80.4±13.3 µm TE/g). Tryptophan showed a moderate degree of anti-inflammatory activity against TNF-α and IL-6. rhIFNγ inhibited tryptophan metabolism. A low concentration of L-tryptophan (10–25 μg/mL) inhibited nearly 25% of cell growth. When U251 cells were treated with 25 μg/mL L-tryptophan and subsequently challenged with 30 ng/mL of human recombinant IFNγ, a significant inhibitory effect on cell growth was observed. Low concentrations of Xanthurenic acid, L-kynurenine, and 3-OH DL kynurenine were found to inhibit cell growth except melatonin and 3-OH anthranilic acid. Melatonin was a strong inducer of TNF-α in RAW cells, whereas 3-OH kynurenine at 25, 50 and 100 µg/mL inhibited IL-6 in RAW cells. No significant change was observed in the IL-8 profile in tryptophan-treated U251 cells except that L-kynurenine at 10 µg/mL produced significantly high level of an inflammatory cytokine IL-8. Melatonin, 3-OH, DL kynurenine at high concentrations (100 µg/mL) induced proliferation of U251 cells. Melatonin seemed to show synergistic effects with recombinant human IFNγ (rhINFγ) in promoting growth of human glioma cells. While treatment of U251 cells with tryptophan alone and subsequent treatment with rhIFNγ inhibited the growth of human cancer glioma cells, and conversely melatonin combined with rhIFNγ promoted growth of the U251 cells. Conclusions: The findings from this study suggest that human milk-derived tryptophan and its metabolites possess strong antioxidant properties. Such effects might play a significant role in regulating the cell proliferation and growth of human cancer cells in a concentration-dependent manner.

Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats

Abstract Objective: The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats. Methods: Rats were subjected to bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin & eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered prior to curcumin treatment in rats followed by AKI. Results: I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection. Conclusion: It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.

The Role of Food Antioxidants, Benefits of Functional Foods, and Influence of Feeding Habits on the Health of the Older Person: An Overview

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer’s disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer’s disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today’s new older person generation.

Antibacterial and Antiinflammatory Properties of Bovine Colostrum

CONTEXT Immunity related disorder is one of the leading causes of disease in the world. Oxidative stress and microbial infections play a major role in inflammation-induced diseases. Bovine colostrum (BC) contains immunoglobulins and lactoferrins which help in building the immunity and protect against the bacterial proliferation and growth. AIM This study was designed to investigate the antimicrobial and antiinflammatory activities of BC. MATERIALS AND METHODS Antimicrobial activity was determined by the pour-plate method using five different strains of bacteria (Gram -ve and +ve), and carrageenan-induced rat paw edema method was used for the evaluation of antiinflammatory activity in adult Wistar rats. Diclofenac was used as standard antiinflammatory drug, and amoxicillin was used as standard antimicrobial agent. RESULTS BC showed significant antimicrobial activity against Escherichia. coli, Staphylococcus. aureus, Proteus. vulgaris, Enterobacter. aerogenes and Salmonella. typhi. At 100 µg/mL of BC, the inhibition zones were found to be 13mm, 11mm, 12mm, 12mm, and 11mm, respectively. The BC zones were comparatively smaller than those of amoxicillin at 10µg/mL, where the inhibition zones were 16mm, 30mm, 23mm, 22mm and 23mm, respectively. In the BC treated animals, the percentage edema inhibition was found to be 67.94% at the third hour, suggesting high antiinflammatory activity of BC in rats. CONCLUSION BC may be beneficial in reducing the risks of inflammation associated diseases. Further studies are needed before BC can be recommended for therapeutic interventions in humans.

Mast cell stabilizers obviate high fat diet-induced renal dysfunction in rats.

The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats.

TNF-α modulation by natural bioactive molecules in mouse RAW 264.7 macrophage cells

Abstract Background: The present study was designed to examine the anti-inflammatory effects of plant-derived products marketed for human health benefits. Methods: The tumor necrotic factor-α (TNF-α) was used as a proinflammatory biomarker generated by mouse macrophage RAW 264.6 cells. The in vitro tested plant products include Saskatoon berry (SKB), quercetin, purified oat beta-glucan (OBG), curcumin, and turmeric. Quantification of TNF-α in cell culture supernatants was carried out using mouse TNF-α assay kit and the cell proliferation was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2,5- diphenyltetrazolium bromide) assay. The cells were grown in Dulbecco’s modified Eagle’s medium supplemented with 10% heat-inactivated fetal bovine serum and 100 U/mL penicillin and 100 µg/mL streptomycin. Bacterial lipopolysaccharide (LPS) at a concentration of 500 ng/mL was employed to stimulate the TNF-α production in mouse macrophage cells. Results: Results showed that curcumin at 10 µM (3.7 µg/mL) level effectively attenuated the LPS-induced inflammatory response, and at 100 µM completely inhibited macrophage RAW cell growth (p<0.05). The aqueous turmeric extract caused inhibitory effect on TNF-α at 25, 50, 100, and 500 µg/mL. SKB inhibited TNF-α production at 50, 100, 500, and 1,000 µg/mL. On the other hand, at 10, 25, 500, and 1,000 µg/mL SKB promoted significant cell growth/proliferation. Quercetin at 10, 25, 50 and 100 µg/mL inhibited TNF-α, but at 500 and 1,000 µg/mL stimulated cell growth. OBG at 10, 25, and 50 µg/mL inhibited TNF-α, but in some cases OBG stimulated TNF-α At 1,000 and 10,000 µg/mL OBG proved to be extremely toxic or lethal to the macrophage cells. Conclusions: Overall, the plant products showed anti-inflammatory effects as well as cell proliferation or inhibition in the in vitro system used in this investigation. The underlying mechanisms of dualistic actions caused by plant-derived ingredients, viz., macrophage cellular growth stimulation or retardation, remain to be elucidated.

Antibacterial activity of combination of synthetic and biopolymer non-woven structures.

Abstract Background: Fibrous structures and synthetic polymer blends offer potential usages in making biomedical devices, textiles used in medical practices, food packaging, tissue engineering, environmental applications and biomedical arena. These products are also excellent candidates for building scaffolds to grow stem cells for implantation, to make tissue engineering grafts, to make stents to open up blood vessels caused by atherosclerosis or narrowed by blood clots, for drug delivery systems for micro- to nano-medicines, for transdermal patches, and for healing of wounds and burn care. The current study was designed to evaluate the antimicrobial activity of woven and non-woven forms of nano- and macro-scale blended polymers having biocompatible and biodegradable characteristics. Methods: The antimicrobial activity of non-woven fibrous structures created with the combination of synthetic and biopolymer was assessed using Gram-negative, Gram-positive bacteria, such as Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Enterobacter aerogenes using pour plate method. Structural evaluation of the fabricated samples was performed by Fourier transform infrared spectroscopy. Results: Broad spectrum antibacterial activities were found from the tested materials consisting of polyvinyl alcohol (PVA) with chitosan and nylon-6 combined with chitosan and formic acid. Conclusions: The combination of PVA with chitosan was more bactericidal or bacteriostatic than that of nylon-6 combined with chitosan and formic acid. PVA combination with chitosan appears to be a broad-spectrum antimicrobial agent.