Thiagarajan Raman

Protective effect of ferulic acid and resveratrol against alloxan-induced diabetes in mice.

The present study was to investigate the effect of ferulic acid and resveratrol on alloxan-induced diabetic mice, through analysis of basic biochemical parameters, enzymic as well as non-enzymic activities, lipid peroxidation and immunohistochemical studies. Alloxan was administered as a single dose (75 mg/kg body weight) to induce diabetes in mice. A dose of ferulic acid (10 mg/kg body weight) and resveratrol (20 mg/kg body weight) were administrated orally, to the alloxan-induced diabetic mice. The levels of basic biochemical markers and lipid peroxidation were significantly (P<0.05) increased in alloxan-induced diabetic mice. The levels of antioxidants were significantly (P<0.05) decreased in liver, kidney and serum. Immunohistochemical studies in alloxan induced mice demonstrated a marked increase in the immunoreactivity of nuclear transcription factor (NF-κB). Treating the diabetic mice with doses of ferulic acid and resveratrol restored the changes in the above parameters analyzed. The present study, showed that ferulic acid and resveratrol exerted antioxidant as well as anti-diabetic effects, consequently alleviate liver, kidney and pancreas damage caused by alloxan-induced diabetes, probably through inhibition of the proinflammatory factor, NF-κB.

Biosynthesis of silver nanoparticles using ethanolic petals extract of Rosa indica and characterization of its antibacterial, anticancer and anti-inflammatory activities.

The present study was aimed at biosynthesis of silver nanoparticles (AgNPs) using ethanolic extract of rose (Rosa indica) petals and testing their potential antibacterial activity using selective human pathogenic microbes, anticancer activity using human colon adenocarcinoma cancer cell line HCT 15 as well as anti-inflammatory activity using rat peritoneal macrophages in vitro. The biologically synthesized AgNPs were also characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The characterized AgNPs showed an effective antibacterial activity against Gram negative (Escherichia coli, Klebsiella pneumoniae) than Gram positive (Streptococcus mutans, Enterococcus faecalis) bacteria. MTT assay, analysis of nuclear morphology, mRNA expression of Bcl-2, Bax and protein expression of caspase 3 as well as 9, indicated potential anticancer activity. In addition, green synthesized AgNPs also attenuated cytotoxicity, nuclear morphology and free radical generation (O2(-) and NO) by rat peritoneal macrophages in vitro. The results of our study show the potential green synthesis of silver nanoparticles in mitigating their toxicity while retaining their antibacterial activities.

Synthesis of silver nanoparticles using Solanum trilobatum fruits extract and its antibacterial, cytotoxic activity against human breast cancer cell line MCF 7

In the present study, we have synthesized silver nanoparticles by a simple and eco-friendly method using unripe fruits of Solanum trilobatum. The aqueous silver ions when exposed to unripe fruits extract were reduced and stabilized over long time resulting in biosynthesis of surface functionalized silver nanoparticles. The bio-reduced silver nanoparticles were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction (XRD). These biologically synthesized silver nanoparticles were tested for its antibacterial activity against few human pathogenic bacteria including Gram-positive (Streptococcus mutans, Enterococcus faecalis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria. In addition, we also demonstrated anticancer activity of these nanoparticles in vitro against human breast cancer cell line (MCF 7) using MTT, nuclear morphology assay, Western blot and RT-PCR expression. These results taken together show the potential applications of biosynthesized silver nanoparticles using S. trilobatum fruits.

Inhibition of diabetic-cataract by vitamin K1 involves modulation of hyperglycemia-induced alterations to lens calcium homeostasis.

This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity. These changes were associated with cataract formation in diabetic animals. By contrast treatment of diabetic rats with vitamin K1 (5 mg/kg, sc, twice a week) resulted in animals with partially elevated blood glucose and with transparent lenses having normal levels of sorbitol, AGE, Ca2+ ATPase, Ca2+, and oxidative stress. Vitamin K 1 may function to protect against cataract formation in the STZ induced diabetic rat by affecting the homeostasis of blood glucose and minimizing subsequent oxidative and osmotic stress. Thus, these results show that Vitamin K1 inhibits diabetic-cataract by modulating lens Ca2+ homeostasis and its hypoglycemic effect through its direct action on the pancreas.

Hyperglycemia-Induced Oxidative-Nitrosative Stress Induces Inflammation and Neurodegeneration via Augmented Tuberous Sclerosis Complex-2 (TSC-2) Activation in Neuronal Cells.

Diabetes is a systemic disease mainly characterized by chronic hyperglycemia and with extensive and long-lasting spiteful complications in central nervous systems (CNS). Astrocytes play an important role in the defense mechanism of CNS, with great ability of withstanding accumulation of toxic substances. Apart from functional disorders, hyperglycemia leads to slow progressive structural abnormalities in the CNS through oxidative stress pathways. However, the molecular mechanism by which neurons die under oxidative stress induced by high glucose (HG) remains largely unclear. Here, we report that HG-induced inflammation and neurodegeneration in brain tissues, brain astrocytes (C6), and pheochromocytoma (PC-12) cells are cultured in HG conditions. Our results show that the increases in phosphorylation of Akt and ERK1/2MAPK are associated with increased accumulations of reactive oxygen species (ROS) in neuronal cells, which simultaneously enhanced phosphorylations of tuberous sclerosis complex-2 (TSC-2) and mammalian target of rapamycin (mTOR) in the diabetic brain and in HG-exposed neuronal cells. Pharmacologic inhibition of Akt or ERK1/2 or siRNA-mediated gene silencing of TSC-2 suppressed the strong downregulation of TSC-2-mTOR activation. Findings of this study also demonstrate that HG resulted in phosphorylation of NF-κB, coinciding with the increased production of inflammatory mediators and activation of neurodegenerative markers. Pretreatment of cells with antioxidants, phosphoinositide3-kinase (PI3-K)/Akt, and ERK1/2 inhibitors significantly reduced HG-induced TSC-2 phosphorylation and restored NF-κB protein expression leading to decreased production of inflammatory mediators and neurodegenerative markers. These results illustrate that ROS functions as a key signaling component in the regulatory pathway induced by elevated glucose in neuronal cell activation leading to inflammation and neurodegeneration.

Lutein and cataract: from bench to bedside

Abstract Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein.

Future prospects of antibacterial metal nanoparticles as enzyme inhibitor.

Nanoparticles are being widely used as antibacterial agents with metal nanoparticles emerging as the most efficient antibacterial agents. There have been many studies which have reported the mechanism of antibacterial activity of nanoparticles on bacteria. In this review we aim to emphasize on all the possible mechanisms which are involved in the antibacterial activity of nanoparticles and also to understand their mode of action and role as bacterial enzyme inhibitor by comparing their antibacterial mechanism to that of antibiotics with enzyme inhibition as a major mechanism. With the emergence of widespread antibiotic resistance, nanoparticles offer a better alternative to our conventional arsenal of antibiotics. Once the biological safety of these nanoparticles is addressed, these nanoparticles can be of great medical importance in our fight against bacterial infections.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

Abstract Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH)2 without any organic molecule (CdO‐1) and calcination of Cd‐citrate coordination polymer (CdO‐2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO‐2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO‐1 nanoparticles. Histopathological observations also support our contention that CdO‐1 nanoparticles showed higher toxicity relative to CdO‐2 nanoparticles. The organic unit of Cd‐citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd2+ ions in CdO‐2 compared to non‐covered CdO‐1 nanoparticles and hence mitigate the toxicity in the case of CdO‐2. This was supported by atomic absorption spectrophotometer analyses of Cd2+ ions release from CdO‐1 and CdO‐2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd2+ from sources such as cigarette smoke. HighlightsToxicity of CdO nanoparticles can be mitigated by the use of sodium citrate.Sodium citrate covers the CdO surface and reduces Cd2+ ion release.Use of sodium citrate reduces both biochemical and histopathological changes.Sodium citrate can be a remediation strategy against CdO nanoparticles toxicity.

Platinum nanoparticles inhibit bacteria proliferation and rescue zebrafish from bacterial infection

Platinum nanoparticles (PtNPs) with potent antibacterial activity were synthesized using pectin and sodium borohydride as capping and reducing agents, respectively. For the first time, the in vivo antibacterial activity of PtNPs was demonstrated using adult zebrafish as the animal model. As a proof of concept, zebrafish infected with a model pathogen, Escherichia coli and a fish-specific pathogen, Aeromonas hydrophila, were subjected to treatment with PtNPs. A bacteria colony count assay revealed that the PtNPs exhibit dose-dependent inhibition of bacterial proliferation and rescued zebrafish completely from bacteria infection. The mechanism of antibacterial action includes the loss of membrane integrity and generation of reactive oxygen species. Toxicology studies reveal that the antibacterial concentration of PtNPs used in this study is non-toxic to zebrafish. Being non-toxic to zebrafish, these PtNPs might open up new avenues in antimicrobial therapy for future biomedical applications.

Magnesium Ion Acts as a Signal for Capsule Induction in Cryptococcus neoformans

Cryptococcal meningitis caused by Cryptococcus neoformans, is a common opportunistic neural infection in immunocompromised individuals. Cryptococcus meningitis is associated with fungal burden with larger capsule size in cerebrospinal fluid (CSF). To understand the role of CSF constituents in capsule enlargement, we have evaluated the effect of artificial CSF on capsule induction in comparison with various other capsule inducing media. Two different strains of C. neoformans, an environmental and a clinical isolates were used in the present study. While comparing the various capsule inducing media for the two different strains of C. neoformans, it was observed that the capsule growth was significantly increased when grown in artificial CSF at pH 5.5, temperature 34°C for ATCC C. neoformans and 37°C for Clinical C. neoformans and with an incubation period of 72 h. In addition, artificial CSF supports biofilm formation in C. neoformans. While investigating the individual components of artificial CSF, we found that Mg2+ ions influence the capsule growth in both environmental and clinical strains of C. neoformans. To confirm our results we studied the expression of four major CAP genes namely, CAP10, CAP59, CAP60, and CAP64 in various capsule inducing media and in different concentrations of Mg2+ and Ca2+. Our results on gene expression suggest that, Mg2+ does have an effect on CAP gene expression, which are important for capsule biosynthesis and virulence. Our findings on the role of Mg2+ ion as a signal for capsule induction will promote a way to elucidate the control mechanisms for capsule biosynthesis in C. neoformans.