Publications by authors named "Phaniendra Alugoju"

12 Publications

  • Page 1 of 1

Molecular mechanisms of action of Trehalose in cancer: A comprehensive review.

Life Sci 2021 Mar 5;269:118968. Epub 2021 Jan 5.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address:

Cellular homeostasis maintained by several cellular processes such as autophagy, apoptosis, inflammation, oxidative stress, aging, and neurodegeneration, contribute to cell growth and development. Cancer cells undergo aberrant changes from a normal cell that show abnormal behaviour such as reduced apoptosis and autophagy, increased oxidative stress and inflammation. Various pharmacological and genetic inhibitors have been reported as drug candidates to control cancer cells, but the use of natural molecules as anti-cancer agents are limited. There is an emerging need for the development of alternative natural therapeutic agents that maintain cellular homeostasis without affecting cell viability and physiology. This review highlights the multifunctional roles of Trehalose, a natural disaccharide that can target various cellular processes in the cancer. Trehalose possessing an antioxidant activity also has effect on cancer, which is explained through targeting cell progression, angiogenesis and metastasis pathways at molecular level targeting EGFR, PI3K, Akt, VEGF and MMP 9 proteins inside the cell.
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http://dx.doi.org/10.1016/j.lfs.2020.118968DOI Listing
March 2021

Effect of short-term oral supplementation of crocin on age-related oxidative stress, cholinergic, and mitochondrial dysfunction in rat cerebral cortex.

Life Sci 2020 Dec 7;263:118545. Epub 2020 Oct 7.

Department of Biochemistry and Molecular Biology, Pondicherry University, India. Electronic address:

Background And Aim: Aging is associated with oxidative stress and altered cholinergic and mitochondrial function. Crocin is a carotenoid antioxidant that quenches free radicals and protects cells and tissues from oxidation in biological systems. The aim of the present study is to investigate the effect of oral supplementation of Crocin on age-associated oxidative stress, cholinergic, and mitochondrial function in rat cerebral cortex.

Main Methods: The middle-aged (15 months old) rats were segregated into three groups (n = 6): Control (ad-libitum fed +0.9% saline as vehicle), Cro 50 (ad-libitum fed + crocin 50 mg/kg/day), Cro 150 (ad-libitum fed + crocin 150 mg/kg/day). The experiment was scheduled for 45 days. The serum and brain parameters were estimated after euthanasia.

Key Findings: Crocin supplementation of Cro 50 and Cro 150 displayed a relative decline in body weight gain during the experimental period and significantly reduced age-associated serum triglyceride level over control. In rat cerebral cortex, age-associated macromolecular damage, decline in endogenous antioxidants and an increase in intracellular calcium concentration were significantly reversed due to oral supplementation of Crocin. Cro 150 significantly improved acetylcholine content as a consequence of acetylcholinesterase inhibition. Further, remarkable mitochondrial function was observed in Cro 150 over the control group as determined by citrate synthase and cytochrome C oxidase enzyme activities.

Significance: Oral supplementation of Crocin significantly reversed age-associated oxidative stress and neuroinflammatory markers. Meanwhile, Cro 150 remarkably improved cholinergic and mitochondrial function over the control group and facilitated further delay in the aging process due to enhanced cognitive effect.
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http://dx.doi.org/10.1016/j.lfs.2020.118545DOI Listing
December 2020

Multifaceted targeting of neurodegeneration with bioactive molecules of saffron (Crocus sativus): An insilco evidence-based hypothesis.

Med Hypotheses 2020 Oct 23;143:109872. Epub 2020 May 23.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

Oxidative stress-mediated neurodegeneration is responsible for 12% mortality around the globe. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are the most prevalent neurodegenerative diseases, associated with modulation of acetylcholine levels and amyloid beta accumulation & dopamine level and alpha-synuclein oligomerization, respectively. Therefore, a better understanding of their pathological mechanisms reveals novel target proteins and encourages exploitation of suitable lead molecules. In the present study, targets for AD and PD were sought not only to suppress the pathological condition but to restore the normal physiological function. In this view, activation of retinoic acid receptor alpha can be formulated as a novel target to improve choline acetyltransferase transcription that works together with acetylcholine esterase and beta-secretase 1 inhibition against AD. Likewise, inhibition of Polo-like kinase 2 fails to phosphorylate alpha-synuclein and motivates efficient autophagic clearance. Therefore, PLK2 inhibition, together with L-DOPA supplementation and monoamine oxidase B inhibition widens the therapeutic options for PD. As oxidative stress is the major factor for neurodegeneration, AMPK activation stabilizes energy metabolism and Sirtuin 1 (histone deacetylase 1) activation enhances AMPK, PGC1a and Nrf gene expressions. Phytochemical extracts from saffron stigma were broadly appreciated on memory enhancement and cognition. However, the exact mechanism was not established. Therefore, this inspires the exploitation of phytochemicals in saffron stigma extract using in-silico tools, to anticipate lead molecules that interact with various neurodegeneration associated protein targets.
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http://dx.doi.org/10.1016/j.mehy.2020.109872DOI Listing
October 2020

Role of quercetin and caloric restriction on the biomolecular composition of aged rat cerebral cortex: An FTIR study.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Sep 14;220:117128. Epub 2019 May 14.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

Aging brain is characterized by a change in biomolecular composition leading to a diverse range of neurological diseases. Anti-aging research is of current interest, to lessen the burden of age-related macromolecular damage through antioxidant supplementation and caloric restriction. However, data concerning the effect of these anti-aging regimens on age-related biomolecular changes in rat brain is still lacking. In the present study, for the first time, we employed Fourier transform infrared (FTIR) spectroscopy, to investigate the effect of quercetin, caloric restriction (CR) and combination of both on alterations in the composition of lipids and proteins of aged rat brain cerebral cortex. Aged male Wistar rats (21 months old) were divided into four groups: Control (CONT), fed pellet diet; Quercetin (QUER), fed quercetin (50 mg/kg/day); CR (caloric restriction) (fed 40% reduced CONT), and CRQ (40% CR and 50 mg/kg/day QUER). Three-month-old rats served as young control (YOUNG). Our short-term study (45 days) shows decreased band area of unsaturated lipids, decreased area ratios of olefinic/lipid and CH antisymmetric stretching (2925 cm)/lipids in CONT group compared to young rats, suggesting age-associated lipid peroxidation in aged rats. A slight decrease in the frequency of CH antisymmetric mode of lipids (whereas no change in CH symmetric mode), but a decrease in bandwidths of both CH antisymmetric and symmetric modes of lipids was observed for CONT group compared to YOUNG. Further, a significant decrease in the peak area of infrared bands of proteins and an increase in the peak area of the CO band of lipids was observed in the CONT group. Our data also show that lower levels of α-helical structures and higher levels of random coils, representing altered protein secondary structure composition in the CONT group compared to YOUNG group. Reduction in neuronal cell density and shrinked nucleus was also observed in aged rats. Increase in the accumulation of oxidative mediated damage to macromolecules and diminished antioxidant levels, could be the possible reason for the age-related alterations in the composition of lipids and proteins. However, the combination of quercetin and CR, but not either treatment alone, significantly prevented the age associated alterations in the lipid and protein profiles in the rat cerebral cortex. Further, our results help to understand the mechanism of action of antioxidants under non-restriction and CR conditions, this might help in the development of novel anti-aging treatments to ameliorate oxidative stress in age-related disorders.
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http://dx.doi.org/10.1016/j.saa.2019.05.033DOI Listing
September 2019

Magnolol protects Saccharomyces cerevisiae antioxidant-deficient mutants from oxidative stress and extends yeast chronological life span.

FEMS Microbiol Lett 2019 04;366(8)

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.

We investigated the protective effect of a natural polyphenol, magnolol, on Saccharomyces cerevisiae cells under oxidative stress, and during aging. Our results showed the sensitivity of S. cerevisiae antioxidant gene deficient mutants (sod1∆, sod2∆, cta1∆, ctt1∆, gtt2∆ and tsa1∆) against hydrogen peroxide (H2O2) and menadione stress was rescued by magnolol as demonstrated in spot and colony forming unit counts. Yeast cells pretreated with magnolol showed decreased intracellular oxidation, lipid peroxidation and an increased level of reduced glutathione. Further, SOD1, CTA1 and GTT2 gene expression was examined by reverse transcription-polymerase chain reaction, and was found that magnolol significantly attenuated the upregulation of SOD1 and CTA1 genes under oxidative stress. Finally, longevity of the wild type and sod1 mutant cells were extended by magnolol, and also enhance stress resistance against oxidant stress during chronological aging.
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http://dx.doi.org/10.1093/femsle/fnz065DOI Listing
April 2019

Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach.

Nutr Cancer 2018 Aug-Sep;70(6):971-983. Epub 2018 Sep 11.

a Department of Biochemistry and Molecular Biology, School of Life Sciences , Pondicherry University , Kalapet , India.

Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.
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http://dx.doi.org/10.1080/01635581.2018.1490445DOI Listing
June 2019

Quercetin enhances stress resistance in mutant cells to different stressors.

J Food Sci Technol 2018 Apr 19;55(4):1455-1466. Epub 2018 Feb 19.

Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, 605 014 India.

The gene is an ortholog of the human () gene. mutant () lacking Tel1p, share some of the cellular defects with mutation that includes prevention of oxidative damage repair, premature aging and apoptosis. In the present study, we investigated the protective effects of quercetin on the sensitivity of yeast cells exposed to oxidative, apoptotic and DNA damaging stress and viability of cells during chronological aging. Quercetin improved the stress resistance of ∆ cells when challenged with oxidants such as hydrogen peroxide (HO), menadine bisulphite (MBS) and tertiary butyl hydroperoxide (t-BHP) by scavenging reactive oxygen species (ROS). Quercetin protected the cells from acetic acid-induced apoptotic cell death and sensitivity against hydroxyurea. We found that quercetin attenuated ROS accumulation and apoptotic markers in cells and therefore an increase in cell viability during chronological aging. Our results from the model, suggest that use of quercetin as a food supplement might alleviate oxidative stress mediated DNA damage, apoptosis and age related damaging effects in AT patients and also improve health beneficial effects in humans.
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http://dx.doi.org/10.1007/s13197-018-3062-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876216PMC
April 2018

Effect of Short-term Quercetin, Caloric Restriction and Combined Treatment on Age-related Oxidative Stress Markers in the Rat Cerebral Cortex.

CNS Neurol Disord Drug Targets 2018 ;17(2):119-131

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry-605 014, India.

Background & Objective: Aging is characterized by gradual accumulation of macromolecular damage leading to progressive loss of physiological function and increased susceptibility to diverse diseases. Effective anti-aging strategies involving caloric restriction or antioxidant supplementation are receiving growing attention to attenuate macromolecular damage in age associated pathology.

Method: In the present study, we for the first time investigated the effect of quercetin, caloric restriction and combined treatment (caloric restriction with quercetin) on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged male Wistar rats. 21 months aged rats were divided into four groups (n=6-8) such as group 1-fed ad libitum (AL); group 2-quercetin supplementation of 50 mg/kg b.w/day for 45 days fed ad libitum (QUER); group 3: caloric restricted (CR) (fed 40% reduced AL for 45 days); group 4-fed 40% CR and 50 mg/kg b.w/day QUER for 45 days (CR + QUER). Group 5-three month age old rats served as young control (YOUNG).

Results: Our results demonstrate that combined treatment of caloric restriction and quercetin significantly improved the age associated decline in the activities of endogenous antioxidant enzymes [such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and glutathione (GSH) content and attenuated elevated levels of protein carbonyl content (PCC), lipid peroxidation, lipofuscin, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, it is also observed that combined treatment ameliorated age associated alterations in acetylcholine esterase (AChE) and adenosine triphosphatases (ATPases) such as Na+/K+-ATPase and Ca+2-ATPase (but not Mg+2- ATPase) enzyme activities.

Conclusion: Finally, we conclude that combined treatment of caloric restriction and quercetin (but not either treatment alone) in late life is an effective anti-aging therapy to counteract the age related accumulation of oxidative macromolecular damage.
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http://dx.doi.org/10.2174/1871527317666180314120507DOI Listing
June 2019

Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.

Curr Microbiol 2018 May 9;75(5):519-530. Epub 2017 Dec 9.

Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, 605 014, India.

The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.
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http://dx.doi.org/10.1007/s00284-017-1412-xDOI Listing
May 2018

Free radicals: properties, sources, targets, and their implication in various diseases.

Indian J Clin Biochem 2015 Jan 15;30(1):11-26. Epub 2014 Jul 15.

Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, 605 014 India.

Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation). Free radicals can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, thereby altering the normal redox status leading to increased oxidative stress. The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders (Parkinson's disease-PD, Alzheimer's disease-AD and Multiple sclerosis-MS), cardiovascular diseases (atherosclerosis and hypertension), respiratory diseases (asthma), cataract development, rheumatoid arthritis and in various cancers (colorectal, prostate, breast, lung, bladder cancers). This review deals with chemistry, formation and sources, and molecular targets of free radicals and it provides a brief overview on the pathogenesis of various diseased conditions caused by ROS/RNS.
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http://dx.doi.org/10.1007/s12291-014-0446-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310837PMC
January 2015

Effects of short term exposure of atrazine on the liver and kidney of normal and diabetic rats.

J Toxicol 2014 29;2014:536759. Epub 2014 Sep 29.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India.

The present study evaluates the effects of short term (15 days) exposure of low dose (300 μg kg(-1)) of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) on antioxidant status and markers of liver and kidney damage in normal (nondiabetic) and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg(-1) could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.
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http://dx.doi.org/10.1155/2014/536759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198780PMC
October 2014

Effects of Atrazine on Reproductive Health of Nondiabetic and Diabetic Male Rats.

Int Sch Res Notices 2014 28;2014:676013. Epub 2014 Oct 28.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.

The aim of the present study was to investigate the effects of low dose of atrazine on reproductive system of male Wistar rats. 16 rats were divided into four groups of four animals each. Group I (nondiabetic) and group III (diabetic) animals served as controls that received safflower oil (300 μL/kg bw/day), respectively. Group II (nondiabetic) and group IV (diabetic) animals received atrazine (300 μg/kg bw/day). Nonsignificant decrease in the activities of antioxidant and steroidogenic enzymes and sperm parameters suggests that atrazine did not produce any effect on reproductive system of rats. Histological findings also revealed that atrazine at a dose of 300 μg/kg bw did not produce any testicular toxic effects in nondiabetic and diabetic atrazine treated rats. Low dose of atrazine did not show reproductive toxicity in rats. To know the effects of atrazine in diabetic rats further studies have to be carried out with increased concentration of atrazine.
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http://dx.doi.org/10.1155/2014/676013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897337PMC
July 2016
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