Publications by authors named "Kozhiparambil Gopalan Raghu"

16 Publications

  • Page 1 of 1

Vanillic acid mitigates the impairments in glucose metabolism in HepG2 cells through BAD-GK interaction during hyperinsulinemia.

J Biochem Mol Toxicol 2021 Mar 2:e22750. Epub 2021 Mar 2.

Biochemistry and Molecular Mechanism Laboratory, Agro-processing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, India.

Glucokinase (GK), a key regulator of hepatic glucose metabolism in the liver and glucose sensor and mediator in the secretion of insulin in the pancreas, is not studied in detail for its therapeutic application in diabetes. Herein, we study the alteration in GK activity during hyperinsulinemia-induced insulin resistance in HepG2 cells. We also investigated the link between GK and Bcl-2-associated death receptor (BAD) during hyperinsulinemia. There are emerging demands for GK activators from natural resources, and we selected vanillic acid (VA) to evaluate its potential as GK activators during hyperinsulinemia in HepG2 cells. VA is a phenolic compound and a commonly used food additive in many food industries. We found that VA safeguarded GK inhibition during hyperinsulinemia significantly in HepG2 cells. VA also prevented the depletion of glycogen synthesis during hyperinsulinemia, which is evident from protein expression studies of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, glycogen synthase, and glycogen synthase kinase-3β. This was associated with activation of BAD activity, which was also confirmed by Western blotting. Molecular docking revealed strong binding between GK active site and VA, supporting their strong interaction. These are the first in vitro data to indicate the beneficial properties of VA with respect to insulin resistance induced by hyperinsulinemia by GK activation. Since it is activated via BAD, the hypoglycemia associated with general GK activation is not expected here and therefore has significant implications for future therapies against diabetes.
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http://dx.doi.org/10.1002/jbt.22750DOI Listing
March 2021

An in vitro study reveals the anti-obesity effects of 7- methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran from Myristica fragrans.

Eur J Pharmacol 2021 Jan 27;891:173686. Epub 2020 Oct 27.

Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, 695019, India. Electronic address:

Adipogenesis, the maturation process of preadipocytes, is closely associated with the development of obesity and other complex metabolic syndromes. Herein, we investigated the effect of 7- methoxy-3-methyl-5-((E)- prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (TM), a benzofuran, isolated from the mace of Myristica fragrans Houtt on adipogenesis in 3T3-L1 preadipocytes to extrapolate whether this compound has any anti-obesity potential. For this, 3T3-L1 preadipocytes were induced to differentiate in the presence of various concentrations of TM (1, 5, 10 μM) and analyzed for triglyceride (TG) accumulation and the expression of proteins and genes involved in lipogenesis and lipolysis associated with adipogenesis. Results showed that TM significantly reduced TG accumulation and expression of marker proteins of adipocyte differentiation (peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and fatty acid-binding protein 4) and increased the secretion of glycerol in a dose-dependent manner. There was a significant dose-dependent decrease in the expression of fatty acid synthase, stearoyl-CoA desaturase-1, sterol regulatory element-binding transcription factor 1c, and acetyl-CoA carboxylase 1 and an increase in carnitine palmitoyltransferase 1, acyl-CoA oxidase, and peroxisome proliferator-activated receptor α in TM treated cells. The phosphorylation of cAMP-activated protein kinase was also increased, which in turn activated the phosphorylation of acetyl-CoA carboxylase in mature adipocytes. Also, there was an increase in glucose uptake by TM, suggesting its insulin-sensitizing potential. This is the first report on the anti-obesity effects of TM from Myristica fragrans on adipogenesis and lipid metabolism in 3T3-L1 adipocytes and demands detailed in vivo study for developing TM as anti-obesity therapeutics.
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http://dx.doi.org/10.1016/j.ejphar.2020.173686DOI Listing
January 2021

An Overview on Arsenic Trioxide-Induced Cardiotoxicity.

Cardiovasc Toxicol 2019 04;19(2):105-119

Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (CSIR - NIIST), Thiruvananthapuram, Kerala, 695019, India.

Arsenic trioxide (ATO) is among the first-line chemotherapeutic drugs used in oncological practice. It has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukaemia. The clinical use of ATO is hampered due to cardiotoxicity and hence many patients are precluded from receiving this highly effective treatment. An alternative to this would be to use any drug that can ameliorate the cardiotoxic effects and allow exploiting the full therapeutic potential of ATO, with considerable impact on cancer therapy. Generation of reactive oxygen species is involved in a wide range of human diseases, including cancer, cardiovascular, pulmonary and neurological disorders. Hence, agents with the ability to protect against these reactive species may be therapeutically useful. The present review focuses on the beneficial as well as harmful effects of arsenic and ATO, the mechanisms underlying ATO toxicity and the possible ways that can be adopted to circumvent ATO-induced toxicity.
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http://dx.doi.org/10.1007/s12012-018-09504-7DOI Listing
April 2019

Significance of mitochondria on cardiometabolic syndromes.

Fundam Clin Pharmacol 2018 Aug 3;32(4):346-356. Epub 2018 May 3.

Agroprocessing and Technology Division, CSIR -National Institute for Interdisciplinary Science and Technology (NIIST), Industrial estate P.O., Pappanamcode, Thiruvananthapuram, 695019, Kerala, India.

Metabolic syndromes (MS) are a cluster of disorders such as obesity, hypertension, dyslipidemia, and diabetes. Cardiometabolic syndrome (CMS), a branch of MS, is a group of diseases affecting cardiovascular, renal, metabolic, prothrombotic, and inflammatory abnormalities due to defects in energy metabolism. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defect in the 1980s, research advances have revealed a number of common human diseases involving mitochondrial dysfunction. One of the major defects in CMS and its associated diseases is excess cellular oxidative stress and oxidative damage to mitochondrial components. In this study, we overview specific aspects of mitochondrial biology that have contributed and likely will continue enhance the progress of development of therapeutics for CMS. During the last decade, however, increasing evidence has emerged supporting the role of mitochondrial functional parameters in the genesis of various metabolism-related disorders. The biochemical pathways which modulate various mitochondrial functional indicators such as mitochondrial biogenesis, mitochondrial membrane potential, electron transport chain and ATP synthesis, intramitochondrial oxidative stress, and mitochondria-mediated cell death have been recognized in diagnosis and prognosis of various disorders associated with energy metabolism and heart function.
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http://dx.doi.org/10.1111/fcp.12359DOI Listing
August 2018

Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in high energy diet rat model.

J Ethnopharmacol 2016 Dec 27;193:500-509. Epub 2016 Sep 27.

Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India. Electronic address:

Ethnopharmacological Relevance: This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model.

Materials And Methods: Experimental groups consisted of normal diet (ND), ND+SCE 500mg/kg bwd, HFS+vehicle, HFS+metformin 100mg/kg bwd, HFS+SCE 250/500mg/kg bwd. Initially the animals were kept under HFS diet for 8 weeks, and at the end of 8 week period, animals were found to develop insulin resistance and dyslipidemia. Post-administration of SCE, metformin or vehicle were carried out for 3 weeks. Gene and protein expressions relevant to insulin signalling pathway were analysed.

Results: HFS significantly altered the normal physiology of animals via proteins and genes relevant to metabolism like stearoyl-CoA desaturase (SCD1), sterol regulatory element binding protein 1 (SREBP-1c), fatty acid synthase (FAS), glucose 6 phosphatase (G6Pase), phosphoenol pyruvate carboxykinase (PEPCK), glucose transporter 2 (GLUT2), protein tyrosine phosphatse 1B (PTP1B), peroxisome proliferator activated receptor alpha (PPAR alpha), sirtuin 1 (SIRT1) and glucokinase. SCE administration attenuates the insulin resistance in HFS rat by the down regulation of SCD1 gene expression that modulates SREBP-1c dependent and independent hepatic lipid accumulation.

Conclusion: SCE enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in HFS rat model.
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http://dx.doi.org/10.1016/j.jep.2016.09.050DOI Listing
December 2016

Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

J Diet Suppl 2016 13;13(3):300-12. Epub 2015 Aug 13.

a Agroprocessing and Natural Products Division , CSIR-National Institute for Interdisciplinary Science and Technology (NIIST) , Pappanamcode , Trivandrum, Kerala , India.

Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p < .05) and increased the activities of antioxidant enzymes like catalase and superoxide dismutase along with increased concentration of non-enzymatic antioxidant, reduced glutathione (GSH). Similarly, BDE caused a significant decrease in the lipid peroxidation (LPO) in the cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.
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http://dx.doi.org/10.3109/19390211.2015.1036186DOI Listing
August 2016

Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes.

Eur J Pharmacol 2015 May 3;754:162-72. Epub 2015 Mar 3.

Agroprocessing and Natural Products Division, Council for Scientific and Industrial Research - National Institute for Interdisciplinary Science and Technology (CSIR - NIIST), Thiruvananthapuram, Kerala 695019, India. Electronic address:

Arsenic trioxide (ATO), though a very effective drug for the treatment of acute promyelocytic leukemia, leads to cardiotoxicity. As mitochondria are the center of attention of cardiac cell׳s general metabolic status, it is primarily important to see the interaction of ATO with mitochondria. Studies related exclusively to the alterations in mitochondria and its associated functions caused by ATO are very limited. The present investigation aims to explore the effect of ATO on various components of electron transport chain, oxygen consumption, ATP production, mitochondrial superoxide generation, transmembrane potential, permeability pore opening, calcium homeostasis and apoptosis. Attempts were also made to see the efficacy of phloretin, a potent antioxidant flavonoid found majorly in apple peel on cardiotoxicity. The H9c2 cells exposed to ATO (5µM) exhibited increased oxidative stress with reduced innate antioxidant status, mitochondrial dysfunctions and apoptosis. It increased the intracellular calcium content, caused alterations in the activity of transcription factor Nrf2, xanthine oxidase, aconitase and caspase 3 compared to the control group. Phloretin at 2.5 and 5µM concentrations were able to protect the cells from ATO toxicity via protecting mitochondria through its antioxidant potential. The present investigation based on mitochondria reveals the probability of cardioprotective potential of phloretin for the cancer patients on ATO chemotherapy.
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http://dx.doi.org/10.1016/j.ejphar.2015.02.036DOI Listing
May 2015

Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3-L1 adipocytes via PPARγ signaling pathway.

Biofactors 2014 Nov-Dec;40(6):646-57. Epub 2014 Dec 20.

Biochemistry and Cell Culture Laboratory, Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, 695019, India.

The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPARγ). Naturally occurring PPARγ modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPARγ activity. In the present work, we studied chebulagic acid (CHA) isolated from fruits of Terminalia chebula with respect to its effect on adipogenesis, glucose transport, and endocrine function of adipocyte. The mRNA expression profile of PPARγ target gene CCAAT/enhancer-binding protein alpha (C/EBP-α) was analyzed by qRT-PCR. The putative binding mode and the potential ligand-target interactions of CHA, with PPARγ was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARγ signaling and adipogenesis dose dependently but in a moderate way, less than rosiglitazone. GLUT4 expression and adiponectin secretion was increased by CHA treatment. The mRNA expression of PPARγ target gene C/EBP-α was increased in CHA -treated adipocytes. The comparison of results of various parameters of adipogenesis, insulin sensitivity, endocrine function and molecular docking experiments of roziglitazone and chebulagic acid indicate that the latter behaves like partial PPARγ agonist which could be exploited for phytoceutical development against T2DM.
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http://dx.doi.org/10.1002/biof.1193DOI Listing
September 2015

Antidiabetic property of Aerva lanata (L.) Juss. ex Schult. is mediated by inhibition of alpha glucosidase, protein glycation and stimulation of adipogenesis.

J Diabetes 2015 Jul 19;7(4):548-61. Epub 2015 Feb 19.

Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research - National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, India.

Background: Diabetes is the leading cause of morbidity and mortality, with a number currently diagnosed as high as 371 million. Plant-based therapy could be an ideal choice because of fewer side-effects and wider acceptability. Hence, the antihyperglycemic potential of Aerva lanata, a herb prescribed for diabetes in Ayurveda was evaluated to elucidate its possible mechanism of action.

Methods: High performance liquid chromatography analysis was used for the characterization of 70% ethanolic (aqueous leaf extract [ALE]) and ethyl acetate (AEA) extracts. Further, they were evaluated for their antioxidant, inhibition of alpha glucosidase, protein glycation dipeptidyl peptidase IV (DPP IV), protein tyrosine phosphatase 1B (PTP1B) and stimulation of glucose uptake and glitazone like property (adipogenic potential) using in vitro models. The promising alpha glucosidase inhibitory potential of ALE was further evaluated in normal and streptozotocin (STZ) diabetic rats.

Results: ALE inhibited yeast (IC50 - 81.76 μg/mL) and rat intestinal alpha glucosidase (IC50 - 108.7 μg/mL), protein glycation, DPP IV enzyme (IC50 - 118.62 μg/mL) and PTP1B (IC50 - 94.66 μg/mL). ALE stimulated maximal adipogenesis at 50 μg/mL and enhanced insulin mediated glucose uptake (threefold of basal) at 100 μg/mL in L6 myotubes. ALE (500 mg/kg b.w.) showed a significant antihyperglycemic activity in sucrose loaded STZ normal (15.57%) and diabetic (18.44%) rats. HPLC analysis of ALE revealed the presence of bioactives like alpha amyrin, betulin and beta sitosterol.

Conclusions: Alpha glucosidase inhibition, antiglycation, and adipogenic potential significantly contribute to the antidiabetic property of Aerva lanata. In addition, insulin sensitization and antioxidant potential also enhance its therapeutic potential.
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http://dx.doi.org/10.1111/1753-0407.12216DOI Listing
July 2015

Curcumin improves hypoxia induced dysfunctions in 3T3-L1 adipocytes by protecting mitochondria and down regulating inflammation.

Biofactors 2014 Sep-Oct;40(5):513-23. Epub 2014 Aug 11.

Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, Kerala, India.

Obesity induced metabolic syndrome is increasing worldwide at an alarming rate. It is characterized by excessive expansion of white adipose tissue which leads to hypoxia and impairs normal metabolism. Recent studies reveal that hypoxia could be one of the factors for inflammation, insulin resistance and other obesity related complications. There is a high demand for anti-obese phytoceuticals to control and manage the complications resulting from obesity. In this study, we investigated how hypoxia affect the physiological functions of 3T3-L1 adipocytes emphasizing on oxidative stress, inflammation, and mitochondrial functions. We also evaluated the protective role of various doses of curcumin, a well-known dietary antioxidant, on hypoxia induced alterations. The results revealed that hypoxia significantly altered the vital parameters of adipocyte biology like HIF 1α expression (103.47% ↑), lactate, and glycerol release (184.34% and 69.1% ↑, respectively), reactive oxygen species production (432.53% ↑), lipid and protein oxidation (376.6% and 566.6% ↑, respectively), reduction in antioxidant enzymes (superoxide dismutase and catalase) status, secretion of inflammatory markers (TNF α, IL 6, IL 1β, and IFN γ), and mitochondrial functions (mitochondrial mass, membrane potential, permeability transition pore integrity, and superoxide generation). Curcumin substantially protected adipocytes from toxic effects of hypoxia in a dose dependent manner by protecting mitochondria and down regulating inflammation. Acriflavine is used as a positive control. A detailed investigation is required for the development of curcumin as an effective nutraceutical against obesity.
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http://dx.doi.org/10.1002/biof.1175DOI Listing
July 2015

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver, kidney, pancreas and eye lens in rats.

Exp Toxicol Pathol 2014 Sep 6;66(7):281-91. Epub 2014 Jun 6.

Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research - National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, Kerala, India. Electronic address:

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg(-1) bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug.
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http://dx.doi.org/10.1016/j.etp.2014.05.004DOI Listing
September 2014

Protective effect of Boerhaavia diffusa L. against mitochondrial dysfunction in angiotensin II induced hypertrophy in H9c2 cardiomyoblast cells.

PLoS One 2014 30;9(4):e96220. Epub 2014 Apr 30.

Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India.

Mitochondrial dysfunction plays a critical role in the development of cardiac hypertrophy and heart failure. So mitochondria are emerging as one of the important druggable targets in the management of cardiac hypertrophy and other associated complications. In the present study, effects of ethanolic extract of Boerhaavia diffusa (BDE), a green leafy vegetable against mitochondrial dysfunction in angiotensin II (Ang II) induced hypertrophy in H9c2 cardiomyoblasts was evaluated. H9c2 cells challenged with Ang II exhibited pathological hypertrophic responses and mitochondrial dysfunction which was evident from increment in cell volume (49.09±1.13%), protein content (55.17±1.19%), LDH leakage (58.74±1.87%), increased intracellular ROS production (26.25±0.91%), mitochondrial superoxide generation (65.06±2.27%), alteration in mitochondrial transmembrane potential (ΔΨm), opening of mitochondrial permeability transition pore (mPTP) and mitochondrial swelling. In addition, activities of mitochondrial respiratory chain complexes (I-IV), aconitase, NADPH oxidase, thioredoxin reductase, oxygen consumption rate and calcium homeostasis were evaluated. Treatment with BDE significantly prevented the generation of intracellular ROS and mitochondrial superoxide radicals and protected the mitochondria by preventing dissipation of ΔΨm, opening of mPTP, mitochondrial swelling and enhanced the activities of respiratory chain complexes and oxygen consumption rate in H9c2 cells. Activities of aconitase and thioredoxin reductase which was lowered (33.77±0.68% & 45.81±0.71% respectively) due to hypertrophy, were increased in BDE treated cells (P≤0.05). Moreover, BDE also reduced the intracellular calcium overload in Ang II treated cells. Overall results revealed the protective effects of B. diffusa against mitochondrial dysfunction in hypertrophy in H9c2 cells and the present findings may shed new light on the therapeutic potential of B. diffusa in addition to its nutraceutical potentials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096220PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005769PMC
November 2014

Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

Food Funct 2014 Mar;5(3):502-11

Agroprocessing and Natural Products Division, Council for Scientific and Industrial Research - National Institute for Interdisciplinary Science and Technology (CSIR - NIIST), Thiruvananthapuram, Kerala 695019, India.

Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.
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http://dx.doi.org/10.1039/c3fo60470eDOI Listing
March 2014

Preparation and characterization of selenium incorporated guar gum nanoparticle and its interaction with H9c2 cells.

PLoS One 2013 30;8(9):e74411. Epub 2013 Sep 30.

Agroprocessing and Natural Products Division, CSIR- National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India.

This study deals with the preparation and characterization of selenium incorporated guar gum nanoparticle (SGG), and its effect on H9c2 cardiomyoblast. Herein, nanoprecipitation techniques had been employed for the preparation of SGG nanoparticle. The prepared nanoparticle had been subjected to various types of analytical techniques like transmission electron microscopy (TEM), X-ray diffraction (XRD) and particle size analysis to confirm the characteristics of nanoparticle as well as for selenium incorporation. Physical characterization of nanoparticle showed that the size of nanoparticles increase upto ∼69-173 nm upon selenium incorporation from ∼41-132 nm. Then the prepared nanoparticles were evaluated for its effect on H9c2 cells. In this regard, the effect of nanoparticle on various vital parameters of H9c2 cells was studied. Parameters like cell viability, uptake of selenium incorporated guar gum nanoparticle by the cells, effect of SGG on DNA integrity, apoptosis, reactive oxygen species generation, alteration in transmembrane potential of mitochondria and cytoskeletal integrity had been investigated. Viability results showed that up to 25 nM of SGG was safe (10.31%) but beyond that it induces cytotoxicity. Cellular uptake of selenium showed that cell permeability for SGG is significantly high compared to normal selenium (7.2 nM of selenium for 25 nM SGG compared with 5.2 nM selenium for 25 nM sodium selenite). There was no apoptosis with SGG and also it protects DNA from hydroxyl radical induced breakage. Likewise no adverse effect on mitochondria and cytoskeleton was observed for 25 nM of SGG. Overall results reveal that SGG is highly suitable for biomedical research application.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074411PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787042PMC
May 2014

An in vitro study reveals nutraceutical properties of Ananas comosus (L.) Merr. var. Mauritius fruit residue beneficial to diabetes.

J Sci Food Agric 2014 Mar 4;94(5):943-50. Epub 2013 Sep 4.

Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research, National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram-, 695019, Kerala, India.

Background: Rapid urbanisation and nutritional transition is fuelling the increased global incidence of type 2 diabetes. Pineapple fruit residue was explored for its nutraceutical properties as an alternative or adjunct to currently available treatment regime. Ethyl acetate and methanolic extracts of pineapple fruit residue were evaluated for anti-diabetic activity in cell free and cell based systems. Specifically, we assessed: (1) antioxidant potential, (2) anti-glycation potential, (3) carbohydrate digestive enzyme inhibition, and (4) lipid accumulation and glycerol-3-phosphate dehydrogenase activity in differentiating 3T3-L1 cells.

Results: The active components in the ethyl acetate and methanolic extracts were identified as sinapic acid, daucosterol, 2-methylpropanoate, 2,5-dimethyl-4-hydroxy-3(2H)-furanone, methyl 2-methylbutanoate and triterpenoid ergosterol using DART/HRMS and ESI/HRMS. Micronutrient analysis revealed the presence of magnesium, potassium and calcium. Adipogenic potential, anti-glycation property of the ethyl acetate extract, and DNA damage protection capacity of the methanolic extract are promising.

Conclusion: Results from this study clearly indicate that pineapple fruit residue could be utilised as a nutraceutical against diabetes and related complications.
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http://dx.doi.org/10.1002/jsfa.6340DOI Listing
March 2014

Desmodium gangeticum (Linn.) DC. exhibits antihypertrophic effect in isoproterenol-induced cardiomyoblasts via amelioration of oxidative stress and mitochondrial alterations.

J Cardiovasc Pharmacol 2013 Jan;61(1):23-34

Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, India.

Cardiac hypertrophy occurs in response to increased workload, such as hypertension or valvular heart disease. Oxidative stress has been implicated in cardiac hypertrophy and in its transition to heart failure. This study was taken up with the objective to evaluate the role of oxidative stress in cardiomyoblast hypertrophy and its modulation by Desmodium gangeticum (DG) that has been traditionally used in Ayurveda, an Indian system of medicine. The methanolic root extract was analyzed for total phenolic content and tested for antioxidant potential. Hypertrophy was induced by exposing H9c2 cell line to β-adrenergic receptor agonist, isoproterenol (ISO), for 96 hours. Analyses of reactive oxygen species (ROS) generation, mitochondrial transmembrane potential ([INCREMENT]Ψm), and integrity of permeability transition were performed in ISO as well as Desmodium and ISO-cotreated cells. The results demonstrated potent free radical scavenging activity of DG. Cell line studies showed significant increase in ROS generation, dissipation of [INCREMENT]Ψm, and permeability transition pore opening in ISO-treated cells. Desmodium was found to attenuate ISO-induced hypertrophy by reduction of ROS generation, restoration of [INCREMENT]Ψm, and prevention of permeability transition pore opening. This study is the first documentation of the modulatory effect of DG on cardiac hypertrophy.
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http://dx.doi.org/10.1097/FJC.0b013e3182756ad3DOI Listing
January 2013