Ravinder Nagpal

Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases.

Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of cholesterol into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile, binding action of bile by fibre, and production of short-chain fatty acids by oligosaccharides. The present paper reviews the mechanisms of action of anti-cholesterolemic potential of probiotic microorganisms and probiotic food products, with the aim of lowering the risks of cardiovascular and coronary heart diseases.

Cancer-preventing attributes of probiotics: an update

Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes β-glucuronidase and β-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory oxidative stress that protects cells against carcinogen-induced damage. These include glutathione-S-transferase, glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. However, there is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence based largely on laboratory studies.

Anti-Inflammatory Treatments for Chronic Diseases: A Review

Inflammation is viewed as one of the major causes for the development of different diseases like cancer, cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, asthma, and CNS related diseases such as depression and parkinsons disease; and this fervent phenomenon provides space for understanding different inflammatory markers. Increasing evidences have elucidated the outcome of inflammatory pathways dysregulation resulting in many symptoms of chronic diseases. The detection of transcription factors such as nuclear factor kappa-B (NF-κB), STAT and their gene products such as COX-2, cytokines, chemokines and chemokine receptors has laid molecular foundation for the important role of inflammation in chronic diseases in which the NF-κB is reported as a major mediator which makes a possible way for the development of new therapeutic approaches using synthetic and natural compounds that might eventually decrease the prevalence of these diseases. Even if many inflammatory markers like TNF-α, IL-1, IL-6, IL-8 and C-reactive protein (CRP) are reported to be the major key factors with proved role in several inflammatory diseases, IL-1 and TNF-α are the important cytokines that can induce the expression of NF-κB which is the potential target in these inflammatory diseases. This review aims to explore and summarize that how some drugs and natural compounds show their modulatory activity in inflammatory pathways and chronic inflammatory markers in these inflammatory diseases.

Molecular approaches for identification and characterization of lactic acid bacteria

The last few years have produced a revolution in the development of very sensitive, rapid, automated, molecular detection methods for a variety of various species of lactic acid bacteria (LAB) associated with food and dairy products. Nowadays many such strains of LAB are considered probiotics. The genome‐based methods are useful in identifying bacteria as a complementary or alternative tool to phenotypical methods. Over the years, identification methodologies using primers that target different sequences, such as the 16S ribosomal RNA (rRNA)‐encoding gene, the 16S‐23S rRNA intergenic spacer region, the 23S rRNA‐encoding, recA and ldhD genes; randomly amplified polymorphic DNA, restriction fragment length polymorphism, denaturing gradient gel electrophoresis, temperature gradient gel electrophoresis, amplification rDNA restriction analysis, restriction enzyme analysis, rRNA, pulse field gel electrophoresis and amplification fragment length polymorphism have played a significant role in probiotic bacteriology. Hence, the aim of this review is to provide an overview of some rapid and reliable polymerase chain reaction‐based molecular methods used for identifying and differentiating closely related species and strains of LAB associated with food and industry.

Biological and medicinal properties of grapes and their bioactive constituents: an update.

The grape is one of the most valued conventional fruits, worldwide. Although most of the parts of the grapevine are useful, primarily, the grape is considered as a source of unique natural products not only for the development of valuable medicines against a number of diseases, but also for manufacturing various industrial products. Over the last few decades, apart from the chemistry of grape compounds, considerable progress has been made towards exploring the biological activities of various grape-derived constituents. Today, it is well established that in addition to serving as food, the grape is a major source of several phytochemicals. The main biologically active and well-characterized constituent from the grape is resveratrol, which is known for various medicinal properties in human diseases. This review discusses the roles of various grape-derived phytochemicals in relation to various diseases.

Anticarcinogenic effect of probiotic fermented milk and chlorophyllin on aflatoxin-B 1 -induced liver carcinogenesis in rats

The present investigation was carried out to evaluate the hepatoprotective effect of probiotic fermented milk (FM) containing Lactobacillus rhamnosus GG and Lactobacillus casei strain Shirota, alone as well as in combination with chlorophyllin (CHL) as an antioxidant agent in male Wistar rats administered aflatoxin-B₁ (AFB₁). AFB₁ was injected intraperitoneally at the rate of 450 μg/kg body weight per animal twice a week for 6 weeks, maintaining an equal time interval between the two consecutive AFB₁ administrations. A total of 125 male Wistar rats were randomly allocated to five groups, each group having twenty-five animals. Group I was offered FM containing L. rhamnosus GG and L. casei strain Shirota. Group II was administered AFB1 and served as the control group; group III was administered FM-AFB₁, in which besides administering AFB₁, FM was also offered. Group IV was offered CHL and AFB₁, and group V was offered both FM and CHL along with AFB₁. The rats were euthanised at the 15th and 25th week of the experiment and examined for the biochemical and hepatopathological profile. A significant reduction in thiobarbituric acid-reactive substances (TBARS) was observed in the FM-CHL-AFB₁ group compared with the AFB1 control group. FM alone or in combination with CHL was found to show a significant (P < 0·05) hepatoprotective effect by lowering the levels of TBARS and by enhancing the activities of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, catalase and glutathione-S-transferase, indicating that probiotic FM alone or in combination with CHL possesses a potent protective effect against AFB₁-induced hepatic damage.

Probiotic metabolites as epigenetic targets in the prevention of colon cancer

Dietary interventions for preventing colon cancer have recently attracted increased attention from researchers and clinicians. The probiotics have emerged as potential therapeutic agents but are also regarded as healthy dietary supplements for nutrition and health applications. The probiotic metabolome may interfere with various cellular and molecular processes, including the onset and progression of colon cancer. Probiotic metabolites may lead to the modulation of diverse cellular signal transduction and metabolic pathways. The gut microbial metabolites (organic acids, bacteriocins, peptides, etc.) have been noted to interact with multiple key targets in various metabolic pathways that regulate cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis, and metastasis. Progress in this field suggests that epigenetic alterations will be widely used in the near future to manage colon cancer. The present review provides insights into the molecular basis of the therapeutic applications and the chemopreventive activities of certain probiotic metabolites, with emphasis on the interaction between these metabolites and the molecular signaling cascades that are considered to be epigenetic targets in preventing colon cancer.

Probiotic Lactobacillus rhamnosus GG and Aloe vera gel improve lipid profiles in hypercholesterolemic rats.

OBJECTIVE The effects of Lactobacillus rhamnosus GG (LGG) and Aloe vera (AV) gel on lipid profiles in rats with induced hypercholesterolemia were studied. METHODS Five treatment groups of rats (n = 7) were the fed experimental diets: a normal control diet, a hypercholesterolemic diet (HD), HD + LGG, HD + AV gel, and HD + LGG + AV gel. RESULTS Supplementation with LGG decreased serum total cholesterol by 32%; however, in combination with AV, the decrease was 43%. The decreases in triacylglycerol levels in the HD + LGG, HD + AV, and HD + LGG + AV groups were 41%, 23% and 45%, respectively. High-density lipoprotein increased by 12% in the HD + LGG + AV group, whereas very low-density and low-density lipoprotein values decreased by 45% and 30%, respectively. The atherogenic index in the HD + LGG + AV group decreased to 2.45 from 4.77 in the HD + LGG group. Furthermore, fecal Lactobacillus species counts increased significantly when LGG was fed in combination with the AV gel. The oral administration of LGG fermented milk alone or in combination with the AV gel increased cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase expression) and absorption (low-density lipoprotein receptor expression), whereas cholesterol 7α-hydroxylase mRNA expression levels were lower in the HD + LGG and HD + LGG + AV groups compared with the control HD group. CONCLUSION The combination of LGG and AV gel may have a therapeutic potential to decrease cholesterol levels and the risk of cardiovascular diseases.

Milk, Milk Products, and Disease Free Health: An Updated Overview

The cow and its milk have been held sacred in the world since the dawn of human civilization. Indian ancient Vedic texts describe the virtues of milk and dairy products, as is authenticated by modern scientific principles and proofs. Therefore, milk has been considered as one of the most natural and highly nutritive part of a daily balanced diet. Currently, the integration of advanced scientific knowledge with traditional information is gaining incredible momentum toward developing the concept of potential therapeutic foods. Furthermore, new advances toward understanding the therapeutic roles of milk and milk products have also given a new impetus for unraveling the age old secrets of milk. At present, the best-known examples of therapeutic foods are fermented milk products containing health promoting probiotic bacteria. In the present article, we have tried to review the various aspects of the therapeutic nature of milk and fermented dairy products in a highly up-dated manner, and offer an in-depth insight into the development of targeted therapeutic future foods as per the requirements of consumers.

Effect of probiotic fermented milk and chlorophyllin on gene expressions and genotoxicity during AFB1-induced hepatocellular carcinoma

The aim of this study was to investigate the chemopreventive effect of probiotic fermented milk and chlorophyllin on aflatoxin B₁ (AFB₁) induced hepatocellular carcinoma. In vivo trials were conducted on 200 Wistar rats allocated to eight groups. Rats in the positive control group were given intraperitoneal injection of aflatoxin B₁ at 450 μg/kg body weight twice a week for 6 weeks. The rats were sacrificed and dissected at 25th week of the experiment, and comet assay was carried out in hepatic cells to assess the genotoxicity or DNA damage. The tumour incidence was decreased by approximately one-third than AFB₁ control group. The expression of c-myc bax, bcl-2, cyclin D1, p53 and rasp-21 genes was also studied. A significant (P<0.05) reduction in DNA damage was observed in probiotic fermented milk with chlorophyllin group as compared to aflatoxin B₁ control group. The c-myc, bcl-2, cyclin D1 and rasp-21 level was found to be highest in AFB₁ control group as compared to the treatment group. The results advocate the enhanced protective potential of probiotic fermented milk and chlorophyllin against AFB₁-induced molecular alterations in hepatic cells during carcinogenesis.