Arumugam Suyavaran

The extra cellular synthesis of gold and silver nanoparticles and their free radical scavenging and antibacterial properties

The bio reduction of chloro auric acid (HAuCl(4)) and silver nitrate (AgNO(3)) is achieved extracellularly by using the aqueous extract of Solanum torvum (S. torvum) fruit. The nanoparticle formation was screened by UV-visible spectroscopy through color conversion due to surface plasma resonance bands at 560 nm and 430 nm for gold and silver nanoparticles respectively. The spherical shapes with smooth surface of gold and silver nanoparticles were analyzed through scanning electron microscope and its presence was confirmed by energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups in the gold and silver salts and the bio interactive functional groups present in the S. torvum extract were characterized by employing Fourier transform infra-red spectroscopy (FTIR). The biomedical properties of gold and silver nanoparticles were premeditated as free radical scavenging activity and antibacterial static agents. Gold and silver nanoparticles serve as strong hydroxyl, superoxide, nitric oxide and DPPH radical scavengers in contrast to their corresponding metal oxides. The radical quenching properties of gold and silver nanoparticles were found to correlate with in vitro DNA protective effect. The silver nanoparticles show strong zone of inhibition against Escherichia coli, Pseudomonas and Bacillus whereas, gold nanoparticles exhibit fair zone of inhibition. To our knowledge this is the first report that S. torvum extract can reduce metal acids to nano materials.

Spectroscopic and molecular docking studies on the interaction of troxerutin with DNA.

Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.

Synthesis and biological evaluation of isoindoloisoquinolinone, pyroloisoquinolinone and benzoquinazolinone derivatives as poly(ADP-ribose) polymerase-1 inhibitors.

A series of novel fused isoquinolinones with isoindoloisoquinolinone, pyroloisoquinolinone, and benzoquinalizinone skeletons were synthesized from corresponding phenethylimides. The isoquinolinone derivatives were evaluated for their protective effect on chicken erythrocytes subjected to oxidative damage. The effect of isoquinolinone derivatives were analysed by estimation of cell viability, antioxidant enzyme activities, DNA damage (comet assay), PARP-1 inhibition assay and molecular docking of the compounds with PARP-1 active site. The compounds CRR-271, CRR-288 and CRR-224+225 showed significant protective effect at 100 μM concentration. The PARP-1 inhibition assay revealed the IC50 values of CRR-271, CRR-288 and CRR-224+225 as <200 nM, further molecular docking studies shows higher binding energies with PARP-1 active site. Interesting findings in this study suggest that the novel isoquinolinone derivatives inhibit PARP-1 activity and protect cells against oxidative DNA damage, which could be implemented in the treatment of inflammatory diseases.

Preconditioning methods in the management of hepatic ischemia reperfusion‐ induced injury: update on molecular and future perspectives.

Hepatic IR (ischemia reperfusion) injury is a commonly encountered obstacle in the post‐operative management of hepatic surgery. Hepatic IR occurs during ‘Pringle maneuver’ for reduction of blood loss or during a brief period of cold storage followed by reperfusion of liver grafts. The stress induced during hepatic IR, triggers a spectrum of cellular responses leading to the varying degrees of hepatic complications which in turn affect the post operative care. Different preconditioning methods either activate or subdue different sets of molecular signals, resulting in varied levels of protection against hepatic IR injury. Yet, there is a serious lacuna in the knowledge regarding the choice of preconditioning methods and the resulting molecular changes in order to assess the efficiency and choice of these methods correctly. This review provides an update on the various preconditioning approaches such as surgical/ischemic, antioxidant, pharmaceutical and genetic preconditioning strategies published during last six years (2009–2015). Further, we discuss the attenuation or inhibition of specific inflammatory, apoptotic and necrotic markers in the various experimental models of liver IR subjected to different preconditioning strategies. While enlisting the controversies in the ischemic preconditioning strategy, we bring out the uncertainties in the existing molecular targets and their reliability in the attenuation of hepatic IR injury. Future research studies would include the novel preconditioning strategies employ i) the targeted gene silencing of key molecular targets inducing IR, ii) hyper expression of beneficial molecular signals against IR via gene transfer techniques. The above studies would see the combination of these latest techniques with the established preconditioning strategies for better post‐operative hepatic management.

Extracellularly synthesized ZnO nanoparticles interact with DNA and augment gamma radiation induced DNA damage through reactive oxygen species

The present study proposes a green synthesis of highly stable and biocompatible ZnO nanoparticles (ZnONPs) using ferulic acid as the reductant. The biosynthesized nanoparticles were characterized by UV-visible spectroscopy, photoluminescence spectroscopy, X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, atomic mass spectroscopy, energy dispersive X-ray spectroscopy and elemental mapping. The characterization results elucidate the formation of crystalline wurtzite structured acicular shaped ZnONPs. Furthermore, the intricate mechanism of ZnONPs–DNA interaction was studied. The binding affinity and mechanism of ZnONPs with calf thymus-DNA interactions were scrutinized and the conformational changes were analyzed. The results reveal the interaction of ZnONPs with DNA in intercalation mode and the values of the binding constant (K) and Stern–Volmer quenching constant (Ksv) were found to be 5.8 × 105 M−1 and 4.1 × 105 M−1, respectively. Furthermore, gamma radiation induced reactive oxygen species (ROS) generation and DNA damage by ZnONPs were analyzed by various spectrophotometric methods, which unveiled the radiosensitizer role of ZnONPs through the significantly increased generation of ROS. Our current experimental evidence explores the ZnONPs’ dual role capacity as DNA binders as well as radiosensitizers. Based on the present research findings we conclude that ZnONPs can be excellent anticancer agents, warranting in vivo studies.

Selenium nanoparticles synthesized in aqueous extract of Allium sativum perturbs the structural integrity of Calf thymus DNA through intercalation and groove binding

Biomedical application of selenium nanoparticles (SeNPs) demands the eco-friendly composite for synthesis of SeNPs. The present study reports an aqueous extract of Allium sativum (AqEAS) plug-up the current need. Modern spectroscopic, microscopic and gravimetric techniques were employed to characterize the synthesized nanoparticles. Characterization studies revealed the formation of crystalline spherical shaped SeNPs. FTIR spectrum brings out the presence of different functional groups in AqEAS, which influence the SeNPs formation and stabilization. Furthermore the different aspects of the interaction between SeNPs and CT-DNA were scrutinized by various spectroscopic and cyclic voltametric studies. The results reveals the intercalation and groove binding mode of interaction of SeNPs with stacked base pair of CT-DNA. The Stern-Volmer quenching constant (KSV) were found to be 7.02×106M-1 (ethidium bromide), 4.22×106 M-1 (acridine orange) and 7.6×106M-1 (Hoechst) indicating strong binding of SeNPs with CT-DNA. The SeNPs - CT-DNA interactions were directly visualized by atomic force microscopy. The present study unveils the cost effective, innocuous, highly stable SeNPs intricate mechanism of DNA interaction, which will be a milestone in DNA targeted chemotherapy.

Probing the interaction of troxerutin with transfer RNA by spectroscopic and molecular modeling

The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: therapeutic potential of NOX2 and p38MAPK inhibitors†

Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the exact role of neutrophils in IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets—NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury. We found that acrolein initiated neutrophil chemotaxis and induced NET release both in vitro and in vivo. Acrolein exposure caused NET induced nuclear and mitochondrial damage in HepG2 cells as well as aggravated the IR injury in rat liver. Pretreatment with F‐apocynin and naringin, efficiently suppressed acrolein induced NET release in vitro. Notably, it suppressed the expression of inflammatory cytokines, P38MAPK‐ERK activation, and apoptotic signals in rat liver exposed to acrolein and subjected to IR. Moreover, this combination effectively attenuated acrolein induced NET release and hepatic IR injury. In the current study we have shown that the acrolein accumulation in liver due to chronic stress, is responsible for neutrophil recruitment and its activation leading to NET induced liver damage during surgery. Our study shows that therapeutic targeting of NOX2 and P38MAPK signaling in patients with chronic hepatic disorders would improve post operative hepatic function and survival.

Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates

Despite zinc oxide nanoparticles (ZnONPs) being increasingly used as carriers in biomedical fields due to their multifaceted properties and therapeutic importance, better understanding of the mechanisms and cellular consequences resulting from their interaction with cells and cellular components has been warranted. In the present study, we investigate the size-dependent interaction of ZnONPs on RBCs, and its impact on cell viability, DNA damage, ROS generation and morphological changes, employing cellular and analytical methods. Size, charge, stability and solubility were confirmed by DLS, zeta potential, ICP-AES and TEM analysis. Further ICP-AES, TEM, spectroscopic observations and cell based assays showed that ZnONPs exhibited a size dependent impact on RBCs and haemoglobin (Hb), particularly size <50 nm. Conversely, ferulic acid (FA) conjugates and serum albumin significantly reduced the adverse effects exhibited by ZnONPs. The extent of DNA damage and ROS generation is comparatively low in ZnONPs-FA than in ZnONPs alone treated cells. Thus our study documents a novel conceptualization delineating the influence of size on the material properties and therapeutic potential of nanoparticle.

Nutrient profile of porridge made from Eleusine coracana (L.) grains: effect of germination and fermentation.

Porridge (koozh) is one of the traditional foods made from Eleusine coracana L. grains (Finger millet). It is a soft food prepared from processed (germinated & fermented) finger millet flour (FMF). However, in the modern world of fast food, koozh is usually prepared from non-processed (non-germinated & non-fermented) FMF. Hence, present study was undertaken to evaluate the macro and micro nutrient contents in koozh prepared from germinated (fermented & non-fermented) and non-germinated (fermented & non-fermented) FMF. Highest protein, carbohydrate and glycoprotein contents were found in koozh prepared from germinated & non-fermented FMF. The free amino acid contents are higher in germinated & fermented condition when compare to other preparations. No significant change was observed in the calorific value of all preparations. There is no statistical difference in macro-nutrients & micro-nutrients minerals such as calcium, iron, magnesium, manganese, phosphorous and zinc among all the preparations. However, copper content is higher in non-germinated condition, whereas selenium, silicon and sulphur are higher in germinated FMF when compared to others. Significant level of total phenol, total flavonoid and free radical scavenging activity was observed in all preparations, which increased further during fermentation. The present observations, lead us to conclude that koozh prepared from germinated & non-fermented FMF contains higher level of carbohydrate, protein and glycoprotein, however germinated & fermented koozh has increased aminoacids, phytochemicals and free radical scavenging activity. Hence it is suggested that the consumption of koozh made from germinated & fermented FMF may provide easily digestible and energetic nutrients for healthier life.