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Krishnendu Manna,1,* Zareen S Khan,2,* Moumita Saha,3,* Snehasis Mishra,3 Nilesh Gaikwad,4 Jatindra Nath Bhakta,1 Kaushik Banerjee,2 Krishna Das Saha3 1Department of Food & Nutrition, University of Kalyani, Nadia, West Bengal, India; 2National Referral Laboratory, ICAR-National Research Centre for Grapes, Pune, Maharashtra, 412307, India; 3Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, 700032, India; 4ICAR-National Research Centre on Pomegranate, Solapur, Maharashtra, 413255, India*These authors contributed equally to this workCorrespondence: Krishna Das Saha, Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, West Bengal, 700032, India, Tel +91 33 2499 5810, Fax +91 33 2473 5197, Email krishna@iicb.res.in Kaushik Banerjee, National Referral Laboratory, ICAR-National Research Centre for Grapes, Pune, Maharashtra, 412307, India, Email kbgrape@yahoo.comObjective: Grape Seed Extract is a natural source of various polyphenols, which have been shown to possess potent antioxidant and free radical-scavenging activities. The earlier studies have reported that grape seed extract exhibits broad-spectrum pharmacological activities. Therefore, studying the hepatoprotective effects and elucidation of mechanisms of action of the Indian Variety, Manjari Medika grape seed extract (GSE), may give an insight into therapeutic benefits. Methotrexate (MTX) is the first-line pharmacological therapy for different rheumatic diseases. The major adverse events such as hepatotoxicity are evident even in the low doses used for the treatment. The present study investigated the role of MTX on hepatic damage in murine liver and the plausible protective effects of the Indian grape variety, Manjari Medika grape seed extract, in ameliorating it.Methods and Results: To assess the hepatological modulation, mice were divided into eight groups to investigate the ameliorative potential of this GSE (75 and 125 mg/kg) and correlate the experimental findings. The active components of the extract were assessed through UPLC-(ESI)-QToF-MS analysis. On the other hand, various biochemical and immunological indices were carried out to correlate the experimental data. The result demonstrated that the prophylactic administration of GSE reduced MTX-induced hepatic toxicity indices, which subsequently restored the hepatic morphological architecture. Moreover, the application of GSE in a dual dosage (75 and 125 mg/kg) suppressed MTX-induced reactive oxygen species generation, followed by lipid peroxidation and cellular nitrite formation. MTX-induced inflammasome activation through the redox-assisted cascade of TLR4/NF-κB signaling was further reduced by applying the GSE. The results showed that the activation of cytoprotective transcription factor Nrf2 enhanced the level of endogenous antioxidants. Furthermore, through the regulation of TLR4/NF-κB and Nrf2/HO-1 axis, this extract could reduce the MTX-mediated hepatic damage.Conclusion: Our findings suggest that Manjari Medika seed extract could be used as a therapeutic agent to relieve the side effects of MTX and other hepatic disorders.Graphical Abstract: Keywords: hepatic fibrosis, Kupffer cells, Manjari Medika grape seed extract, proanthocyanidins, inflammasome, antioxidant response

Objective: The local thermoregulation in testis is important for optimum spermatozoa development. Excessive heat hampers this regulation resulting in alteration of normal testicular function. The present investigation confirms the role of free radicals in hyperthermia induced oxidative damage in testis and elucidates the dose-dependent ameliorating effect of resveratrol (RSV) against testicular oxidative damage. The aim of the present investigation is also to observe the role of selective concentration of RSV on heat induced oxidative changes in the damaged tissue. Methods: 48 male Wister rats were exposed to hyperthermic condition for the past 7 days of the total 21 days of experiment. RSV was pre- and co-treated with heat stress daily in a dose-dependent manner (1 mg, 5 mg, and 10 mg/kg body weight) for 21days. Results: Reactive oxygen species level was estimated using flow cytometry. Enhancement of hepatotoxicity markers in serum, lipid peroxidation and decreasing antioxidant status in the testis homogenate demonstrated that the oxidative damage in heat exposed tissue. Conclusion: Histological study along with biochemical and molecular assessment of the redox balance of testicular tissue in the present study revealed that RSV significantly ameliorated the heat induced damage in testis. The findings suggest that RSV is an effective antioxidant polyphenolic compound that can protect testis against hyperthermia induced oxidative damage.

Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO2) nanoparticles can manifest either anti- or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO2 nanoparticles of different concentrations (5–100 μg/mL) in the culture media. The half maximal inhibitory concentration (IC50) of nanoceria for HCT 116 is found to be 50.48 μg/mL while that for the HEK 293 cell line is 92.03 μg/mL. To understand the intricate molecular mechanisms of CeO2-induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.

Aim: Tannic acid and vitamin E loaded-poly D, L-lactide-co-glycolic acid (PLGA) nanoparticles (NP) were developed to achieve hepatoprotection in alcoholic liver disease mice model. Materials & methods: PLGA NPs were formed by emulsion solvent evaporation and characterized and delivered to mice. Histology studies were performed, serum enzyme levels of AST, ALT and inflammatory cytokines were checked using ELISA kits. Confocal microscopy and western blot analysis were utilized to determine protein expression levels, and docking studies were performed for interaction analysis. Results: PLGA NPs provided hepatoprotection by reducing inflammatory load, preventing reactive oxygen species generation and apoptosis, as well as by inhibiting the EGFR-AKT-STAT3 pathway. Conclusion: PLGA NPs of tannic acid and vitamin E could be a future medication for alcoholic liver disease treatment.

Biosensors are rational or scientific devices that are generally used to convert any measurable and biochemical signal of a molecule or chemical entity into an analytical and useful, visual outcome based on physicochemical principle. A wide variety of stimulus are generally used by biosensors to transform qualitative or quantitative changes to identifiable or recognizable signals. They are of great benefit to society in current pandemic situations possessing huge potentials not only in the field of detection but also in diagnosis, prognosis and treatment. In contemporary times, diseases and infections have greatly increased taking a huge toll on health expenditure of individuals, overall quality of life and even mortality of persons at a time. Applications include early detection of disease, disease prognosis, biomolecule recognition, surveillance, monitoring, identification, etc. Besides, they also play a phenomenal role in pathogens or microbial identification and detection of various other lethal microbes in food, medication, various matrices and systems, diseased and infectious conditions and are being widely used nowadays. Many electronics as well as instrument manufacturers are currently investing in this burgeoning domain knowing that this health sector holds great promise and rewards. Massive progress and advancement have been witnessed in this scientific field in the past few years and expected to maintain this snowballing trend. Research and development (R & D) in modern micro-level and nanolevel sensor systems serves to associate multidimensions like biology, chemistry, nanoscience and physics, by the amalgamation of various fields such as nanomaterials, electrical circuits, chemicals, sensors, probes, etc. One of the most important areas of focus nowadays is the manufacture of specific, cost-effective and multiplexed or versatile bio-sensing devices that can be used in diverse fields of medicine and disease. This chapter explores the importance of the application of biosensors, their use, and current and future trends in the field of disease diagnosis, along with their advantages and disadvantages.

Cancer detection and diagnosis are grounded mainly on the identification of several unfamiliar features of abnormal cells such as atypical mutations in genetic materials (i.e., genes), qualitative as well as quantitative variations in vital proteins function and quantities, and also detecting changes in various physiological and morphological properties like differences in structure, adhesive properties, elasticity, etc., along with biochemical processes. The most exciting and fascinating techniques currently employed for cancer diagnosis are biosensor analytical devices, which generally comprise a biological component and a physicochemical detector. Biosensor enables the attachment of a wide variety of analyte or chemicals of interest (e.g., macromolecules, chemicals, metabolites, toxins, etc.) in a biologic material (e.g., tissue, cells, organs, organoids, surfaces, etc.) or any such related sample to a probe and their fruitful identification and occasionally their quantification. The biosensors can be broadly classified according to the type of transducer or biorecognition elements present in the sensor and the type of analyte detected, and the mechanism/principle of detection. Most analysis performed by the biosensors requires the labeling of the analyte with a specific indicator. However, efforts are directed at eliminating such challenges, and currently, many techniques are being developed that allows readily direct detection of analytes without prior tagging or labeling. The most common or widespread “label-free” biosensors for cancer detection employs optoelectronic phenomena like surface plasmon resonance or piezoelectric techniques like quartz crystal microbalance. This chapter considers some of the currently available biosensors’ presently used diagnostic and prognostic tools for cancer development. Besides, we shall give details and theoretical insights into their current research trends, along with advantages and disadvantages.

Cancer is among the leading causes of death worldwide. Most cancers represent specific symptoms; however, to comprehend and understand them we need proper diagnostic measures and the expertise of experienced health personals. There are also screening tests available for particular cancer types. The major challenges for the physicians are that cancer symptoms are often overlapped with related benign disease, and thus the importance of accurate diagnostics has grown to offer conclusive evidence of cancer being a possible explanation of the symptoms. New biomarkers and methods are emerging to improve cancer diagnosis; classification of cancer subtypes, prognosis, and prediction of response to therapy is also becoming more convenient with the modernization of available techniques. In practice, a cancer diagnosis has become easier in the past decade with the inclusion of recent techniques as well as further development of relatively old diagnostic procedures. The major concern of any cancer diagnostic is its accuracy, with the least false-positive or false-negative results, as well as it should be timely with early presentation of any symptoms. Any diagnostic test can falls between perfect and useless test and no diagnostic test can absolutely tell us if a patient has a particular disease or not, with cancer diagnostics are no exception. The diagnostic test should also be configured to detect almost any target, their requirement for minimal quantities of sample, and their ability to be automated. Improved diagnostics are also making it possible to understand tumorigenesis, metastasis, and other disease processes. Diagnostic tests based on such information should enable more precise and objective decision-making about cancer staging, progression, and response to therapy. This chapter deals with the different diagnostic measures applied for the detection of malignancy, describing both the conventional methods and associated modifications to them. This chapter also highlights the diagnostic features of some common cancers. The novel modifications and future possible diagnostic tools are also discussed in detail with important attributes of diagnosis especially in relation to cancer.

Moumita Saha,1 Krishnendu Manna,2 Krishna Das Saha1 1Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India; 2Department of Food and Nutrition, University of Kalyani, Kalyani, West Bengal, IndiaCorrespondence: Krishna Das Saha, Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal, 700032, India, Tel +91 33 2499 5810, Fax +91 33 2473 5197, Email krishna@iicb.res.inBackground: NLRP3 inflammasome activation plays a critical role in mediating inflammation and NASH (non-alcoholic steatohepatitis) progression that ultimately leads to cirrhosis and hepatocellular carcinoma. Melatonin (MLT) controls high-fat diet-induced NASH in the murine model by modulating NLRP3 mediated inflammation. P2X7R-mediated inflammasome activation is reported in several inflammatory models including NASH.Objective: The role of MLT in P2X7R-mediated inflammation in the NASH model has not yet been explored. The present study investigated the role of MLT in amending high-fat diet-induced nonalcoholic steatohepatitis in the murine liver.Methods: To evaluate the hepatological changes, mice were divided into four groups to investigate the improvement potential of this MLT (10 and 20 mg/kg) and to assess the experimental findings. Histology, biochemical assays, ELISA, FACS analysis, Western blotting, and IF were performed to assess the physical and molecular changes upon melatonin treatment.Results: The result demonstrated that MLT administration reduced HFD (high-fat diet)-induced non-alcoholic steatohepatitic indices, which successively restored the hepatic morphological architecture and other pathophysiological features too. Moreover, the application of MLT suppressed HFD-induced activation of the inflammasome and through TLR4/NF-κB signaling. Herein, we report that MLT significantly suppresses P2X7R expression and calcium influx along with inflammasome in both in vitro and in vivo. The docking study revealed a strong binding affinity of MLT with P2X7R. Moreover, the results also showed that the Nrf2 level was boosted which may normalize the expression of antioxidant proteins that safeguard against oxidative damage triggered by inflammation. Furthermore, some matrix metalloproteinases like MMP 2 and MMP 9 were repressed and TIMP-1 level was increased, which also signifies that MLT could improve liver fibrosis in this model.Conclusion: Based on our findings, this study may conclude that MLT could be used as a therapeutic agent in the high-fat diet-induced NASH model as it has persuasive anti-inflammatory potential.Graphical Abstract: Keywords: melatonin, NASH, NAFLD, inflammasome, P2X7, inflammation, Kupffer cells

Quercetin has been found to possess diverse pharmacological properties including in different types of cancers. The application of quercetin in the pharmaceutical field is limited due to its poor bioavailability resulting from poor water solubility and poor permeability. We report a systematic chemical modification of quercetin toward the development of semisynthetic derivatives through a selective synthetic methodology, which enables the installation of different substitutions at C-3′ and C-5 positions of quercetin. The hypothesis of the present manuscript was to modulate the log D value and aqueous solubility of quercetin through the attachment of some facilitator moieties. The semisynthetic derivatives with an ideal log D value and improved aqueous solubility will possess a better cell-penetrating ability compared to quercetin. Representative compound 17 shows 96-fold increase in the cytotoxic activity in HCT-116 colon cancer cells as compared to quercetin. The in vivo treatment of 17 in CT-26 tumor-be...

Aim: The present work provides first-time empirical and molecular interaction evidence to establish the higher biofunctionality of a therapeutic lipid, α-eleostearic acid (ESA), encapsulated in a novel and thoroughly characterized biocompatible nanoemulsion (NE) system (particle size

The development of drug carriers based on nanomaterials that can selectively carry chemotherapeutic agents to cancer cells has become a major focus in biomedical research. A novel pH-sensitive multifunctional envelope-type mesoporous silica nanoparticle (SBA-15) was fabricated for targeted drug delivery to human colorectal carcinoma cells (HCT-116). SBA-15 was functionalized with folic acid (FA), and the material was loaded with the water-insoluble flavonoid, quercetin (QN). Additionally, acid-labile magnetite Fe3O4 nanoparticles were embedded over the FA-functionalized QN-loaded monodisperse SBA-15 to prepare the highly orchestrated material FA-FE-SBA15QN. The in vitro and in vivo anti-carcinogenic efficacy of FA-FE-SBA15QN was carried out to explore the pH-sensitive QN release with putative mechanistic aspects. FA-FE-SBA15QN caused a marked tumor suppression, and triggered mitochondrial-dependent apoptosis through a redox-regulated cellular signaling system. Furthermore, FA-IO-SBA-15-QN initiated the c-Jun N-terminal Kinase (JNK)-guided H2AX phosphorylation, which relayed the downstream apoptotic signal to the phosphorylate tumor suppressor protein, p53. On the other hand, the selective inhibition of heat shock protein-27 (HSP-27) by FA-FE-SBA15QN augmented the apoptotic fate through JNK/H2AX/p53 axis. The in vitro and in vivo magnetic resonance imaging (MRI) studies have indicated the theranostic perspective of the composite. Thus, the result suggested that the newly synthesized FA-FE-SBA15QN could be used as a promising chemo theranostic material for the management of carcinoma.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Gold nanoparticle formulated tannic acid (AuNP-TA) was synthesized, and its anticancer activity was compared to that of free tannic acid (TA). The half maximal inhibitory concentration (IC50) was reduced by half when cell lines were treated with AuNP-TA as compared to IC50 values upon free TA treatment. Both showed better cytotoxic activity in HCT116 cell line as compared to MCF7 and HepG2. AuNP-TA induced death of HCT116 cells was associated with characteristic apoptotic changes. At the same treatment dose, AuNP-TA generated more ROS, caused a more extensive DNA damage and promoted higher expression of p53 and p21 than TA. Treatment with AuNP-TA regulated generation of p53 and ROS bi-directionally. Binding studies showed that TA lowered the expression of Akt, which inhibited the survival of colon cancer cells. Also, cell cycle arrest at the G2/M phase, enhanced expression of caspase-3/9, Bak, and Bax, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in AuNP-TA treated HCT116 cells. Thus, AuNP-TA is more efficient than TA in inducing apoptotic cell death of HCT116 cells via the ROS/P53/Akt axis.

Organic-inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated Fe

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated. The spherical nanosized particles showed slow, sustained release in vitro. Moreover, CHR-NP dramatically reduced the serum IgE, ovalbumin (OVA)-induced lung histological alteration, as well as Th2 (T-helper 2) cytokines in the bronchoalveolar lavage fluid (BALF). It also suppressed the elevated serum pro-inflammatory cytokines and their upstream TLR/NF-κB/NLRP3 pathway activation in lung superior to CHR and almost identical to dexamethasone (DEX). Thus this study suggests the potentiality of CHR-NP in ameliorating allergic asthma progression.

Five new coordination polymers (CPs) namely, [{Zn(μ2-H2O)0.5(5N3-IPA)(2,2'-bpe)}]∞ (1), [{Zn(μ2-H2O)0.5(5N3-IPA)(1,10-phen)}]∞ (2), [{Zn(5N3-IPA)(1,2-bpe)}]∞ (3), [{Zn(5N3-IPA)(1,2-bpey)}]∞ (4), and [{Zn(H2O)(5N3-IPA)(4,4'-tme)}(H2O)0.5]∞ (5) (5N3-H2IPA = 5-azidoisophthalic acid, 2,2'-bpe= 2,2'-bipyridine, 1,10-phen = 1,10-phenanthroline, 1,2-bpe = 1,2-bis(4-pyridyl)ethane, 1,2-bpey = 1,2-bis(4-pyridyl)ethylene, 4,4'-tme = 4,4'-trimethylenedipyridine), have been synthesized based on a mixed ligand approach adopting a solvothermal technique. Depending upon the intrinsic structural flexibility of the bis-pyridyl coligands, interesting structural topologies have also been observed in the resulting CPs: Sra SrAl2 type topology for 3 and a 3-fold interpenetrated dmp topology for 4. A green hand grinding technique has been implemented to reduce the particle size of the CPs to generate nanoscale CPs (NCPs). SEM studies of NCPs reveal the formation of square and spherical particles for NCP 1 and 2, respectively, and nano rod for NCP 3, 4, and 5. Remarkably, when scaled down to nano range all the NCPs retain their crystalline nature. The cytotoxic activity of the NCPs (1-5) has been studied using human colorectal carcinoma cells (HCT 116). Significant cell death is observed for NCP 2, which is further corroborated by cell growth inhibition study. The observed cell death is likely to be due to mitochondrial-assisted apoptosis as is evident from immunofluorescence study.

Tender coconut water (TCW), a well-known plant beverage, has been used as a stress-relieving traditional medicine since ancient times. It is also used to treat various ailments of disease, including hepatic disorders, renal disorders, gastric disorders and reproductive disorders. However, the reasons for its effectiveness as a natural antioxidant as well as its testicular protective effects against whole body heat stress (HS)-induced oxidative imbalance remain to be revealed. The present study aimed to elucidate the protective efficacy of TCW on HS-induced testicular damage in a murine system and to explore the possible mechanism of action. Standardized liquid chromatography-mass spectrometry (LC-MS) was used to detect the presence of active components in TCW. Male Wistar rats were exposed to acute HS with or without TCW treatment to evaluate the degree of testicular damage, which was monitored through histological as well as biochemical analysis. Assessment of endogenous antioxidant response and the modulation of signaling pathways associated with inflammation were also subjected to immunofluorescence and flow cytometric evaluation. Acute hyperthermia caused an elevation of excess generation of oxygen radicals following the suppression of antioxidant capacity and augmentation of lipid peroxidation in murine testicles, which was restored by treatment with TCW. The results also demonstrated marked phosphorylation of IKKα/β and IκBα following the activation of NF-κB-guided pro-inflammation upon HS. TCW treatment reversed the HS-induced proinflammatory state through activation of the Nrf2-assisted antioxidant response, which restored the testicular damage. TCW provided competent scientific evidence to substantiate the claims for its use in the treatment of HS-induced inflammation and inflammation-mediated testicular damage.

We report a new highly crystalline 2D π-conjugated hexagonal mesoporous covalent organic framework material, TrzCOF, through the solvothermal polycondensation of 1,3,5-tri(4-formylbiphenyl) benzene [Ph7(CHO)3, TFBPB] with 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and it displayed excellent anticancer activity for human colorectal carcinoma HCT-116 cells.

Cancer is one of the most deadly diseases worldwide. Although several chemotherapeutic agents are available at present for its treatment, they have their own limitations. The main problems of these chemotherapeutic agents are cost involvement and severe life-threatening antagonistic effects. Here, we report a new biodegradable N-rich porous organic polymer methylenedianiline-triformyl phloroglucinol (MDTFP-1) synthesized via a Schiff base condensation reaction between two reactive monomers, that is, 4,4′-methylenedianiline and 2,4,6-triformyl phloroglucinol under inert atmosphere. Because this porous polymer contains polyphenolic building units and has a high Brunauer–Emmett–Teller surface area (283 m2 g–1), it has been explored in the anticancer activity using HCT 116, A549, and MIA PaCa-2 cell lines. We have carried out the flow cytometric assessment using Annexin-V-FITC/PI staining through the exposed level of phosphatidylserine in the outer membrane of cells with MDTFP-1-induced apoptosis. Our results suggested that apoptosis of cells have been enhanced in a time-dependent manner in the presence of this novel porous polymer.

The current investigation has identified the biomarkers associated with severity of disability and correlation among plethora of systemic, cellular and molecular parameters of intellectual disability (ID) in a rehabilitation home. The background of study lies with the recent clinical evidences which identified complications in ID. Various indicators from blood and peripheral system serve as potential surrogates for disability related changes in brain functions. ID subjects (Male, age 10 ± 5 yrs, N = 45) were classified as mild, moderate and severe according to the severity of disability using standard psychometric analysis. Clinical parameters including stress biomarkers, neurotransmitters, RBC morphology, expressions of inflammatory proteins and neurotrophic factor were estimated from PBMC, RBC and serum. The lipid peroxidation of PBMC and RBC membranes, levels of serum glutamate, serotonin, homocysteine, ROS, lactate and LDH-A expression increased significantly with severity of ID whereas changes in RBC membrane β-actin, serum BDNF, TNF-α and IL-6 was found non-significant. Structural abnormalities of RBC were more in severely disabled children compared to mildly affected ones. The oxidative stress remained a crucial factor with severity of disability. This is confirmed not only by RBC alterations but also with other cellular dysregulations. The present article extends unique insights of how severity of disability is correlated with various clinical, cellular and molecular markers of blood. This unique study primarily focuses on the strong predictors of severity of disability and their associations via brain-blood axis.

Krishnendu Manna,1,* Snehasis Mishra,1,* Moumita Saha,1 Supratim Mahapatra,1 Chirag Saha,1 Govind Yenge,2 Nilesh Gaikwad,2 Ramkrishna Pal,2 Dasharath Oulkar,3 Kaushik Banerjee,3 Krishna Das Saha1 1Cancer Biology and Inflammatory Disorder Division, Council of Scientific & Industrial Research–Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India; 2Postharvest Technology Laboratory, Indian Council of Agricultural Research-National Research Centre on Pomegranate, Solapur 413255, Maharashtra, India; 3National Referral Laboratory, Indian Council of Agricultural Research-National Research Centre for Grapes, Pune 412307, Maharashtra, India *These authors contributed equally to this work Background: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer.Purpose: This study was designed to investigate the ameliorative role of pomegranate peel extract–stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model.Methods: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence.Results: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic β-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis.Conclusion: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN. Keywords: pomegranate polyphenol, gold nanoparticle, diabetic kidney disease, advanced glycation end-product, NF-κB, STAT3, Nrf2

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

The lymphatic organ, the spleen, is of immense immunological importance as it is the largest blood filter in the mammalian system. The objective of the current study is to explore the detrimental cellular and sub-cellular effects in the spleen, mediated by the widely used herbicide, paraquat (PQ). PQ is an uncoupling agent for the electron transport chain complex in the mitochondria, which promulgates serious alterations in the intracellular oxidative microenvironment. This leads to the activation of a cascade of sub cellular events leading to cell death. Since PQ-induced oxidative damage in the spleen is not well explored, we planned to develop a PQ toxicity model in rodents, addressing its negative effects in the highest molecular terms. The toxicity markers were evaluated in terms of oxidative stress, cellular apoptosis, inflammation and splenomegaly in Swiss albino mice after treatment with PQ. The increase in thiobarbituric acid reactive substances (TBARS), tissue nitrite formation, intracellular reactive oxygen species (iROS) production, depletion of the activities of catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and the reduction in mitochondrial inner trans membrane potential (MMP) were significant in the PQ treated group compared to the control. A pronounced inhibition of cell proliferative response and increased p53, Bax expression, caspase 3 activities and decreased Bcl-2 were also associated with PQ-induced apoptosis. Moreover, a pro-inflammatory response was apparent in the PQ treated group as indicated by elevated levels of pro-inflammatory markers (TNF-α, IL-6 and COX-2). Thus, this is perhaps the first mechanistic report showing how a herbicide induces the oxidative stress responsible for immunomodulation, apoptosis, as well as splenomegaly in the murine system.

Organic-inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated Fe2O3 nanoparticles with excellent colloidal stability in water using a hydrothermal method for the theranostics applications. The attachment of FA to Fe2O3 was confirmed using various spectroscopic techniques including FTIR and picosecond resolved fluorescence studies. The nanohybrid (FA-Fe2O3) is a combination of two nontoxic ingredients FA and Fe2O3, showing remarkable photodynamic therapeutic (PDT) activity in human colorectal carcinoma cell lines (HCT 116) via generation of intracellular ROS. The light induced enhanced ROS activity of the nanohybrid causes significant nuclear DNA damage, as confirmed from the comet assay. Assessment of p53, Bax, Bcl2, cytochrome c (cyt c) protein expression and caspase 9/3 activity provides vivid evidence for cell death via an apoptotic pathway. In vitro magnetic resonance imaging (MRI) experiments in folate receptor (FR) overexpressed cancer cells (HCT 116) and FR deficient human embryonic kidney cells (HEK 293) reveal the target specificity of the nanohybrid towards cancer cells, and are thus pronounced MRI contrasting agents for the diagnosis of colorectal cancer.

The spleen is a crucial organ manifesting immune functions. Thus, radiation-induced oxidative challenge is vulnerable for the spleen. Our major objective was to protect the spleen from radiation-induced anomalous situations and to identify the signaling pathways involved.Swiss albino mice were treated with ferulic acid (FA) once in a day at a dose of 50 mg/kg body weight for 5 consecutive days before exposing them to single dose of 10 Gy irradiation. The ROS generation and MMP change were determined by flow cytometry. The expression of different signaling proteins was investigated by immunoblotting and immunocytochemistry.FA pretreatment significantly prevented radiation-induced oxidative stress by downregulating TBARS formation and by upregulating SOD and catalase activity. FA scavenged ROS, prevented the alteration of MMP and downregulated the expression of stress marker Cdc42 and apoptotic markers pFA prevented the activation of apoptotic signaling events in the spleen by interfering with the free radical chain reaction and by scavenging superfluous ROS. This is perhaps the first comprehensive study with a mechanistic viewpoint that FA can protect the spleen from ionizing radiation.

The major drawback of anticancer therapy is the development of resistance against drugs and radiation at the later phase of treatment which may lead to recurrences of the disease. Therefore, strategy was taken to enhance radiation sensitivity of lung (A549) and liver (HepG2) carcinoma cells by treatment with ferulic acid (FA) prior to irradiation. FA pre-treatment initially decreased reactive oxygen species (ROS) level in carcinoma cells which induced reductive stress and cytostasis. To overcome this stress, cellular mechanism increased the Keap1 level to down-regulate nuclear localisation of Nrf2 and its dependent antioxidant system. The antioxidant system reached the lowest level after 3 and 6 h of FA treatment in A549 and HepG2 cells respectively. As endogenous ROS were still being generated at same rate, ROS level was clearly higher than control which changed the reductive stress to oxidative stress. Exposure to γ-radiation in this condition further increased ROS level and caused radio-sensitisation of carcinoma cells. Combination of irradiation (IR) and FA activated mitochondrial apoptotic pathway and concomitantly inhibited the cell cycle progression and survival pathway over the IR group. Moreover, the combination treatment showed significant tumour regression, caspase 3 activation and nuclear fragmentation in tumour tissue compared to radiation alone. In contrast, FA pre-treatment protected peripheral blood mononuclear cells (PBMC) and normal lung fibroblast WI38 cells from radiation damage. Together, combination treatment offers effective strategy of killing cancer cells and demonstrates its potential for increasing the efficacy of radio-therapy.

Correction for ‘A new triazine based π-conjugated mesoporous 2D covalent organic framework: its in vitro anticancer activities’ by Sabuj Kanti Das et al., Chem. Commun., 2018, 54, 11475–11478.

Understanding the mechanism of ionizing radiation (IR)-induced systemic stress and its modulation by phytocomponents has great significance for the development of novel phyto-radioprotectors. The present study was intended to evaluate the radioprotective effect of naringin (NG), a citrus flavonoid on the modulation of IR-induced activation of the redox-regulated signaling system in murine liver. On the basis of survival analysis, mice were treated with 75 mg kg−1 body weight of NG for three consecutive days before irradiation (6 Gy). Pretreatment with NG significantly prevented the IR-induced generation of intracellular reactive oxygen species (ROS), along with the formation of hepatic thiobarbituric acid reactive substances (TBARS) and cellular nitrite. NG also showed significant reduction in IR-induced nuclear DNA damage through the inhibition of DNA-dependent protein kinase (DNA-PK). Further, the IR-induced cell death was arrested in the presence of NG through the inhibition of p53 mediated stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) pathways and modulation of other molecules of apoptosis pathways. Moreover, NG supported the intracellular defense mechanisms, by maintaining the endogenous antioxidants probably through phosphoinositide 3-kinase/protein kinase-B (PI3K/Akt) guided transcriptional activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, NG inhibited IR-induced inflammation through suppression of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) followed by the alteration of pro inflammatory factors. Taken together, these results suggested that NG reversed the IR-induced redox-imbalance in murine liver, probably by the inhibition of ROS/p38-MAPK/NF-κB, along with the activation of the PI3K/Akt/Nrf2 pathway and the reduction of apoptosis by interfering with the p53/SAPK/JNK/Bax pathway.

Radioprotective action of gossypetin (GTIN) against gamma (γ)-radiation-induced oxidative stress in liver was explored in the present article. Our main aim was to evaluate the protective efficacy of GTIN against radiation-induced alteration of liver in murine system. To evaluate the effect of GTIN, it was orally administered to mice at a dose of 30 mg/kg body weight for three consecutive days prior to γ-radiation at a dose of 5 Gy. Radioprotective efficacy of GTIN were evaluated at physiological, cellular, and molecular level using biochemical analysis, comet assay, flow cytometry, histopathology, immunofluorescence, and immunoblotting techniques. Ionizing radiation was responsible for augmentation of hepatic oxidative stress in terms of lipid peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and immunofluorescence studies showed that irradiation enhanced the nuclear translocation of nuclear factor kappa B (NF-κB) level, which leads to hepatic inflammation. To investigate further, we found that radiation induced the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment ameliorated these radiation-mediated effects. This is the novel report where GTIN rationally validated the molecular mechanism in terms of the modulation of cellular signaling system’ instead of ‘ This is the novel report where GTIN is rationally validated in molecular terms to establish it as promising radioprotective agents. This might be fruitful especially for nuclear workers and defense personnel assuming the possibility of radiation exposure.

The adverse effects of ionizing radiation occur due to the generation of reactive oxygen species (ROS). The aim of this study was to identify the protective effects of naringin (NG), a citrus flavonoid, on ionizing radiation (IR)-induced differential stress response, with an exploration of the mechanisms involved in this process. Isolated murine splenocytes were incubated in the presence and in the absence of different concentrations of NG (50 and 100 μM) for 1 h prior to 6 Gy γ-irradiation, and the molecular mechanisms of action were determined through biochemical, immunoblot, flow cytometric, and immunofluorescence studies. Pretreatment with NG significantly prevented IR-induced intracellular ROS generation, thereby preventing the formation of cellular TBARS and the development of cellular nitrite. NG significantly reduced nuclear DNA damage with respect to the irradiated splenocytes, through the inhibition of DNA-PKcs and p-γH2AX. The reduced cell viability as a result of irradiation was recovered by NG through modulation of the redox-regulated cell signaling system. NG pretreatment resulted in significant inhibition of IR-induced G1/S phase cell cycle arrest through the modulation of p53-dependent p21/WAF1, cyclin E, and CDK2 activation. The results also demonstrated that NG blocked the IR-induced p38 function and reversed IR-mediated differential stress response through inhibition of the NF-κB pathway. Thus, the p38/NF-κB pathway participated in the IR-induced inflammatory development, leading to upregulation of CRP, MCP-1, and iNOS2 gene expression. However, NG pretreatment reversed the inflammatory development through downregulation of NF-κB, and regulated the expression of CRP, MCP-1, and iNOS2. The above results provide a theoretical basis for the preventive use of NG against radiation-induced multiple cellular anomalies.

Covalent organic frameworks (COFs) having periodicity in pores of nanoscale dimensions can be suitably designed for the organic building units bearing reactive functional groups at their surfaces. Thus, they are an attractive option as an anticancer agent to overcome the limitations of chemotherapy. Herein, we first report a new porous biodegradable nitrogen containing COF material, EDTFP-1 (ethylenedianiline-triformyl phloroglucinol), synthesized using 4,4′-ethylenedianiline and 2,4,6-triformylphloroglucinol via Schiff base condensation reaction. EDTFP-1 exhibited 3D-hexagonal porous structure with average pores of ca. 1.5 nm dimension. Here, we have explored the anticancer potentiality of EDTFP-1. Result demonstrated an enhanced cytotoxicity was observed against four cancer cells HCT 116, HepG2, A549, and MIA-Paca2 with significant lower IC50 on HCT116 cells. Additionally, EDTFP-1-induced cell death was associated with the characteristic apoptotic changes like cell membrane blebbing, nuclear DNA fragmen...

To evaluate the protective effect of gossypetin (GTIN) against gamma (γ)-radiation-mediated DNA damage.Increasing concentrations (10-150 μM) of GTIN were incubated with supercoiled DNA 1 h prior exposure to γ-radiation in the range of 5-Gy absorbed dose from Co(60) γ source. To establish the effective protective concentration of GTIN, supercoiled DNA was pre-incubated with 50 μM of GTIN for 1 h followed by exposure of 5, 10 and 20 Gy doses of γ-radiation. Moreover, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical, nitric oxide (NO) scavenging, metal chelating activity and ferric reducing antioxidant power (FRAP) of GTIN were measured and compared with standards. The flowcytometric analysis and radiation-induced genomic DNA damage by comet assay were employed to estimate the level of intracellular reactive oxygen species (ROS) using isolated murine hepatocytes.GTIN was able to effectively scavenge different free radicals in in vitro situations. It could significantly prevent radiation induced supercoiled and genomic DNA damage with reduced comet parameters. It also acted as a potent scavenger of the radiation induced ROS.GTIN ameliorated radiation-induced oxidative stress and DNA damage by its free-radical scavenging activity.

Whole body radiation exposure causes extensive physiological stress which may prove fatal if it is not appropriately managed. The current study is intended to evaluate the radioprotective effects of epicatechin (EC) in terms of amelioration of radiation induced hepatic and testicular oxidative stress. Swiss albino mice were administered with EC for three consecutive days before exposing them to a single dose of 5-Gy 60 Co gamma (γ) irradiation. Mice were necropsied and liver and testis were taken for biochemical tests for the detection of hepatic and testicular oxidative stress markers. To determine the oxidative stress developed after radiation SGOT, SGPT and ALP were measured to assess the alterations in liver function, reduced glutathione (GSH) content and lipid peroxidation (LPO) were also determined from liver homogenate. To evaluate oxidative stress of testis, LPO, Alkaline Phosphatase (ALP) and Acid Phosphatase (ACP) were also evaluated. Whole body gamma radiation enhanced SGOT, SGPT and ALP level increased as also LPO and depleted GSH level in liver homogenate. Testicular damage was prominent since LPO and ACP level enhanced where as ALP level decreased. Epicatechin pretreatment ameliorated all these gamma radiation mediated alterations and improved the mice from the situation of oxidative stress. Thus, epicatechin pretreatment ameliorated radiation mediated systemic oxidative stress which also prevented liver and testis from further damage.

The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy (60)Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.

Smokeless tobacco (SLT) or chewing tobacco is very common addiction practice in India across the ages making a somber threat and huge disease burden. Oral use of SLT is often assorted with many ingredients and is capable to induce extreme toxicological challenges and carcinogenic developments. The current study investigated the systemic stress in human subjects using blood parameters of SLT chewers. Perturbations in parameters of metabolism, inflammation, RBC morphology and enhanced apoptosis of PBMC in SLT-chewers compared to non-chewer human subjects were found. The study further delved whether SLT mediated any neurodegeration. In vitro studies using SLT showed the neuronal cell death in a dose dependent manner compromising the mitochondrial health. Apoptosis was induced with the consequence of generation of reactive species, induction of DNA damage, alteration of membrane potential, mitochondrial morphology, activation of caspase-cascade, apoptotic proteins and disruption of the neuronal cytoskeleton network. To correlate the neurobiological insult of SLT, mouse behavioral studies with open-field test and plus maze and molecular analyses were investigated. This unique mechanistic study with molecular mechanism validated fatal effects of SLT and SLT-mediated neuronal cell death.

Smokeless tobacco (SLT) remains a threat amongst a large population across the globe and particularly in India. The oral use of tobacco has been implicated to cause physiological stress leading to extreme toxicological challenge. The study included 47 SLT-users and 44 non-users providing a spectrum of pathophysiological, clinico-biochemical, antioxidant parameters, cell cycle progression study of PBMC and morphological changes of red blood cells (RBC). The expressions of p53, p21, Bax, Bcl-2, IL-6, TNF- α, Cox-2, iNOS were analyzed from thirteen representative SLT-users and twelve non-users. Difference in CRP, random glucose, serum cholesterol, TG, HLDL-C, LDL-C, VLDL-C, neutrophil count, monocyte count, ESR, SOD (PBMC) and TBARS (RBC membrane) were found to be statistically significant (p

Four water-soluble dinuclear Zn(II) complexes (1–4) of compartmental ligand L = 2,6-bis(R-iminomethyl)-4-R′-phenolate (where R = N-ethylpiperidine or R = N-ethylpyrrolidine, R′ = methyl or tert-butyl) have been synthesized, characterized, and their DNA cleavage activity and cytotoxicity toward HepG2 cancerous cells are evaluated. The dinuclear complexes are formed by a pentadentate-substituted phenolate ligand chelating the metal ions separated by ca 3.27 A. Each metal is a distorted trigonal bipyramid, completing the coordination sphere through acetate. The X-ray structural determination of 2 shows that the complex is counterbalanced by half (formulation [Zn2L2(CH3CO2)2][(Zn(SCN)4]0.5), while in 1 and 3 two crystallographically-independent complexes are present in the unit cell with a . Among the four complexes only the 4-tert-butyl-phenolato derivatives (3 and 4) show DNA cleavage activity in in-vivo conditions and appear to be promising toward metal complexes to be used as anticancer agents. The cytoto...

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation.

The present study demonstrates for the first time the protective role of two common flavonoids, quercetin and its glycone rutin, against high cholesterol diet (2%) induced hepatotoxicity and inflammation. Swiss albino mice were given either a standard laboratory diet (control), high cholesterol diet (HCD) or high cholesterol diet along with quercetin or rutin (100 mg kg−1 body weight) in their respective groups. The HCD mice exhibited a gain in body weight, significant rise in serum and hepatic level of total cholesterol, triglyceride, liver function enzymes, lipid peroxidation, and pro-inflammatory cytokines (P < 0.05). Histopathological studies showed hepatic fat accumulation and tissue disintegration. There was significant depletion of major hepatic antioxidants (P < 0.05). Immunoblot studies revealed a high expression of redox sensitive transcription factors NF-κB and TNF-α. A subsequent rise in the mRNA expression of inflammatory markers like C reactive protein and inducible nitric oxide synthase 2 were also found from the RT-PCR study. Simultaneous treatment with quercetin or rutin along with HCD significantly prevented the gains in body weight, lipid level, liver function enzymes, lipid peroxidation level and expression of inflammatory markers. The restoration of hepatic antioxidant homeostasis and hepatic morphology has also been observed. Hence, the present study illustrates the hypolipidemic, hepatoprotective and anti-inflammatory effects of two similar flavonoids.

Reaction of ZnII-acetate with two N, N, O-donor Schiff-base ligands, HL1 {4-Chloro-2-[(2-morpholin-4-yl-ethylimino)-methyl]-phenol} and HL2 {4-Chloro-2-[(3-morpholin-4-yl-propylimino)-methyl]-phenol}, which are formed in situ via condensation of 5-chlorosalicylaldehyde and N-(2-aminoethyl/propyl)morpholine, produce one tri- and one mononuclear species, Zn3L1(OAc)4 (1) and ZnL2(OAc) (2). The hypothetical ZnL1(OAc) and Zn3L2(OAc)4 are energetically unfavorable by 9.2 and 5.1 kcal/mol, in compare with their respective real counterparts 1 and 2 evidenced from DFT calculations. Both 1 and 2 catalyze the hydrolytic cleavage of phosphoester bond of (4-nitrophenyl) phosphate where 1 shows higher activity than that of 2. The proposed mechanistic pathways of phosphatase activity of 1 and 2 and the higher efficiency of the latter have been rationalized by DFT study. DNA cleavage activities have been investigated using supercoiled pET28a plasmid DNA where both the complexes show dose dependent DNA cleavage activity with varying degree. Complex 1 shows excellent breakage activity even at a concentration of 20 μM. However, in both cases hydroxyl radical pathway is most probably operative in DNA cleavage activity.