Department Of Zoology
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Item Connecting the Link between Oxidative Stress, Dietary Antioxidants and Hypertension(CRC Press, 2023-06-12T00:00:00) Kaur, Sukhchain; Midha, Tushar; Dutta, Oyndril; Saini, Om Prakash; Muduli, Rasmi Ranjan; Mantha, Anil K.; Dhiman, MonishaCardiovascular disorders such as hypertension, coronary heart disease (CHD), cerebrovascular disease, etc. accounts for millions of deaths per year and among these, hypertension (i.e. increased blood pressure) acts as a silent killer and is responsible for 7.5 billion deaths worldwide. Previously, abnormal functioning of the Renin Angiotensin Aldosterone System (RAAS) was considered as a risk factor for hypertension but in recent times, oxidative stress is a key factor in exaggerating the disease progression. In hypertension, oxidative stress damages the biomolecules, decreases the NO availability and endothelial functioning. The use of external antioxidants as therapeutic agents is an excellent approach in the treatment of hypertension. These antioxidants can reverse the deleterious effects of oxidative stress and recover normal cellular homeostasis. The book chapter is focused on the various natural antioxidants and their role as anti-hypertensive agents. � 2024 selection and editorial matter, Victor R. Preedy, Vinood B. Patel, and Rajkumar Rajendram.Item Bioremediation: A favorable perspective to eliminate heavy metals from polluted soil(Elsevier, 2022-09-30T00:00:00) Kaur, Sukhchain; Midha, Tushar; Verma, Harkomal; Muduli, Rasmi Ranjan; Dutta, Oyindril; Saini, Omprakash; Prakash, Richa; Sharma, Sandeep; Mantha, Anil K.; Dhiman, MonishaThe heavy metal contamination in the environment causes serious risk and long-term lethal effects to all living organisms due to their ability to show toxicity at low concentrations. The bio-magnification of heavy metals in the food chain is a matter of concern for public health. The persistent exposure to heavy metals such as mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), and uranium (U) cause several pathologic conditions in humans by interfering with normal cellular processes. Due to the non-biodegradable nature of these pollutants, they get accumulated for a long time in the soil. The removal of these pollutants by conventional methods is not satisfactory due to the high cost and generation of huge quantities of waste products. Hence, the use of micro-organisms is the most successful approach to remediate heavy metals from the environment due to their efficacy and financial viability. Numerous microorganisms have been employed to diminish the toxic effects of heavy metals. The combination of microorganisms and plants as a bioremediation strategy is another efficient method for heavy metal bioremediation. The chapter will summarize the heavy metal exploitation with a focus on Cd, As, Pb, and Chromium (Cr). It will also describe the various bioremediation techniques which are being used in the removal of these heavy metals from soil. � 2023 Elsevier Inc. All rights reserved.Item Herbal Remedies for Improving Cancer Treatment Through Modulation of Redox Balance(Springer Singapore, 2022-09-28T00:00:00) Kaur, Sukhchain; Verma, Harkomal; Kaur, Sharanjot; Singh, Subham; Mantha, Anil K.; Dhiman, MonishaThe redox modulation induced by oxidative stress is one of the major cause of the metabolic and inflammatory disorders including cancer. The reactive oxygen species (ROS) produced by various sources in the cell shift the redox homeostasis of cells towards more oxidizing or acidic environment. This shift results in the alterations of normal physiologic functioning of biomolecules as well as causes damage to these biomolecules (proteins, lipids, and DNA/RNA). The excessive ROS and redox modulation are the key factors that support growth, progression, and survival of cancer cells. ROS-induced redox modulation further activates pro-tumorigenic cellular pathways for e.g., PI3K/AKT, HIF-1, and MAPK signaling pathways as well as hinders epigenetic signaling. Increasing evidences demonstrate that long-term side effects of anti-cancer chemotherapy are major concern of medical sciences although modern treatments are quite effective. The combination of various herbal formulations with anti-cancer therapy shows improvement in treatment effectiveness in cancer patients. Bioactive compounds present in herbal formulations possess antioxidant and anti-cancer properties that help in the regulation of redox status of cancer cells. The synergetic effects of herbal remedies along with conventional treatment are proven as novel therapeutics in cancer progression management. Clinical studies have shown that broad range of herbs and bioactive compounds from various plants having antioxidant, anti-inflammatory properties can suppress the carcinogenesis. In this chapter we will discuss the role of various plants such as Glycyrrhiza glabra, Picrorhiza kurroa, Tinospora cordifolia, Curcuma longa, Ocimum sanctum, Viola odorata, and bioactive compound ferulic acid found in various cereals. The chapter will also focus on various mechanisms involved in the modulation of chemo-toxicity and improvement of efficacy of conventional anti-cancer therapies by these plants. � Springer Nature Singapore Pte Ltd. 2022.Item Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo(Elsevier Ltd, 2021-07-30T00:00:00) Khan, Iliyas; Sarkar, Bibekananda; Joshi, Gaurav; Nakhate, Kartik T.; Ajazuddin; Mantha, Anil K.; Kumar, Raj; Kaul, Ankur; Chaturvedi, Shubhra; Mishra, Anil K.; Gupta, UmeshThe proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 � 4.27 nm in size, having 0.112 � 0.035 PDI, with -10.1 � 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 � 1.58 and 11.98 � 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice. � 2021 The Author(s)Item Mitigation of Gliadin-Induced Inflammation and Cellular Damage by Curcumin in Human Intestinal Cell Lines(Springer, 2021-01-04T00:00:00) Gupta, Kunj Bihari; Mantha, Anil K.; Dhiman, MonishaWheat is a major diet from many years; apart from its nutritious value, the wheat protein gliadin is responsible for many inflammatory diseases like celiac disease (CD), and non-celiac gluten sensitivity (NCGS). In this study, the gliadin-induced inflammation and associated cellular damage along with the protective role of curcumin was evaluated using human intestinal cell lines (HCT-116 and HT-29) as a model. Cells were cultured and exposed to 160 ?g/ml of gliadin, 100 ?M H2O2, and 10 ?M curcumin (3 h pretreatment) followed by the assessment of inflammation. Spectrophotometric methods, real-time-PCR, ELISA, Western blotting, and confocal microscopy techniques were used to assess inflammatory markers such as advanced oxidation protein products (AOPPs) level, activity of myeloperoxidase (MPO) and NADPH oxidase (NOX), cytokines, and cell damage markers. The results show that gliadin increases the AOPPs level and the activity of MPO and NOX expression. It enhances inflammation by increasing expression of pro-inflammatory cytokines, altered expression of anti-inflammatory, and regulatory cytokines. It exacerbates the cellular damage by increasing MMP-2 and 9 and decreasing integrin ? and ? expression. Gliadin promotes disease pathogenesis by inducing the inflammation and cellular damage which further alter the cellular homeostasis. The pretreatment of curcumin counteracts the adverse effect of gliadin and protect the cells via diminishing the inflammation and help the cell to regain the cellular morphology suggesting phytochemical-based remedial interventions against wheat allergies. � 2021, Springer Science+Business Media, LLC, part of Springer Nature.Item Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II.(Wiley, 2018) Kaur, G; Cholia, RP; Joshi, G; Amrutkar, SM; Kalra, S; Mantha, Anil K.; Banerjee, UC; Kumar, R.The design and synthesis of dihydropyrazolo[1,5‐c]quinazolines (1a–h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compounds, 1b and 1h, were found to be potent cytotoxic agents against glioma cells and exerted selective TopoII inhibitory activity. Furthermore, the compounds induced alterations in reactive oxygen species levels as measured by DCFDA assay and were found to induce cell cycle arrest at the G1 phase at lower concentrations and profound apoptosis at higher concentrations. The interaction of selected investigational molecules with TopoII was further corroborated by molecular modeling.Item Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors.(Elsevier, 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, VinodMonoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1-21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 µM concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders.Item Common geometric basis for apurinic/apyrimidinic endonuclease catalytic activity in structurally non-homologous APE1 and Endonuclease IV.(2013) Tsutakawa, S.E.; Shin, D.S.; Mol, C.D.; Izumi, T.; Arvai, A.S.; Mantha, Anil K.; Szczesny, B.; Ivanov, I.N.; Hosfield, D.J.; Frankel, K.A.; Hitomi, K; Cunningham, R. P.; Tainer, J. A.Item Indian herbs and their therapeutic potential against Alzheimer’s disease: What makes them special? Neuroprotective Effects of Phytochemicals in Neurological Disorders.(2016) Kaur, Navrattan; Sarkar, Bibekananda; Gill, Iqbal; Kaur, S; Mittal, Sunil; Dhiman, Monisha; Padala, Prasad R; Perez-Polo ,Regino; Mantha, Anil K.Item Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors(Academic Press Inc., 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, VinodMonoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1?21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 ?M concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders. ? 2018 Elsevier Inc.
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