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4. Identification of a second 16-hydroxytabersonine-O-methyltransferase suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in Catharanthus roseus

Author

Lemos Cruz, Pamela, Carqueijeiro, Ines, Koudounas, Konstantinos, Bomzan, Dikki Pedenla, Stander, Emily Amor, Abdallah, Cécile, Kulagina, Natalja, Oudin, Audrey, Lanoue, Arnaud, Giglioli-Guivarc’h, Nathalie, Nagegowda, Dinesh A, Papon, Nicolas, Besseau, Sébastien, Clastre, Marc, and Courdavault, Vincent

Published
2023
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19. Betulinic acid mitigates oxidative stress-mediated apoptosis and enhances longevity in the yeast Saccharomyces cerevisiae model

Author

Sudharshan, S. J., Narayanan, Ananth Krishna, Princilly, Jemima, Dyavaiah, Madhu, and Nagegowda, Dinesh A.

Subjects
General Medicine, Biochemistry
Abstract

Betulinic acid (BA), a pentacyclic triterpenoid found in certain plant species, has been reported to have several health benefits including antioxidant and anti-apoptotic properties. However, the mechanism by which BA confers these properties is currently unknown. Saccharomyces cerevisiae, a budding yeast with a short life cycle and conserved cellular mechanism with high homology to humans, was used as a model for determining the role of BA in aging and programmed cell death (PCD). Treatment with hydrogen peroxide (H2O2) exhibited significantly increased (30–35%) survivability of antioxidant (sod1Δ, sod2Δ, cta1Δ, ctt1Δ, and tsa1Δ) and anti-apoptotic (pep4Δ and fis1Δ) mutant strains when cells were pretreated with BA (30 µM) as demonstrated in spot and CFU (Colony forming units) assays. Measurement of intracellular oxidation level using the ROS-specific dye H2DCF-DA showed that all tested BA-pretreated mutants exhibited decreased ROS than the control when exposed to H2O2. Similarly, when mutant strains were pretreated with BA and then exposed to H2O2, there was reduced lipid peroxidation as revealed by the reduced malondialdehyde content. Furthermore, BA-pretreated mutant cells showed significantly lower apoptotic activity by decreasing DNA/nuclear fragmentation and chromatin condensation under H2O2-induced stress as determined by DAPI and acridine orange/ethidium bromide staining. In addition, BA treatment also extended the life span of antioxidant and anti-apoptotic mutants by ∼10–25% by scavenging ROS and preventing apoptotic cell death. Our overall results suggest that BA extends the chronological life span of mutant strains lacking antioxidant and anti-apoptotic genes by lowering the impact of oxidative stress, ROS levels, and apoptotic activity. These properties of BA could be further explored for its use as a valuable nutraceutical.

Published
2023
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21. Identification of a second 16-hydroxytabersonine-O-methyltransferase suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in Catharanthus roseus

Author

Lemos Cruz, Pamela, primary, Carqueijeiro, Ines, additional, Koudounas, Konstantinos, additional, Bomzan, Dikki Pedenla, additional, Stander, Emily Amor, additional, Abdallah, Cécile, additional, Kulagina, Natalja, additional, Oudin, Audrey, additional, Lanoue, Arnaud, additional, Giglioli-Guivarc’h, Nathalie, additional, Nagegowda, Dinesh A, additional, Papon, Nicolas, additional, Besseau, Sébastien, additional, Clastre, Marc, additional, and Courdavault, Vincent, additional

Published
2022
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26. Betulinic acid mitigates oxidative stress-mediated apoptosis and enhances longevity in the yeast Saccharomyces cerevisiae model.

Author

Sudharshan, S. J., Krishna Narayanan, Ananth, Princilly, Jemima, Dyavaiah, Madhu, and Nagegowda, Dinesh A.

Subjects
BETULINIC acid, SACCHAROMYCES cerevisiae, APOPTOSIS, NUCLEAR fragmentation, LIFE cycles (Biology), LONGEVITY
Abstract

Betulinic acid (BA), a pentacyclic triterpenoid found in certain plant species, has been reported to have several health benefits including antioxidant and anti-apoptotic properties. However, the mechanism by which BA confers these properties is currently unknown. Saccharomyces cerevisiae, a budding yeast with a short life cycle and conserved cellular mechanism with high homology to humans, was used as a model for determining the role of BA in aging and programmed cell death (PCD). Treatment with hydrogen peroxide (H2O2) exhibited significantly increased (30–35%) survivability of antioxidant (sod1Δ, sod2Δ, cta1Δ, ctt1Δ, and tsa1Δ) and anti-apoptotic (pep4Δ and fis1Δ) mutant strains when cells were pretreated with BA (30 µM) as demonstrated in spot and CFU (Colony forming units) assays. Measurement of intracellular oxidation level using the ROS-specific dye H2DCF-DA showed that all tested BA-pretreated mutants exhibited decreased ROS than the control when exposed to H2O2. Similarly, when mutant strains were pretreated with BA and then exposed to H2O2, there was reduced lipid peroxidation as revealed by the reduced malondialdehyde content. Furthermore, BA-pretreated mutant cells showed significantly lower apoptotic activity by decreasing DNA/nuclear fragmentation and chromatin condensation under H2O2-induced stress as determined by DAPI and acridine orange/ethidium bromide staining. In addition, BA treatment also extended the life span of antioxidant and anti-apoptotic mutants by ∼10–25% by scavenging ROS and preventing apoptotic cell death. Our overall results suggest that BA extends the chronological life span of mutant strains lacking antioxidant and anti-apoptotic genes by lowering the impact of oxidative stress, ROS levels, and apoptotic activity. These properties of BA could be further explored for its use as a valuable nutraceutical. [ABSTRACT FROM AUTHOR]

Published
2022
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39. Alternative splicing creates a pseudo-strictosidine β-d-glucosidase modulating alkaloid synthesis in Catharanthus roseus

Author

Carqueijeiro, Inês, primary, Koudounas, Konstantinos, additional, Dugé de Bernonville, Thomas, additional, Sepúlveda, Liuda Johana, additional, Mosquera, Angela, additional, Bomzan, Dikki Pedenla, additional, Oudin, Audrey, additional, Lanoue, Arnaud, additional, Besseau, Sébastien, additional, Lemos Cruz, Pamela, additional, Kulagina, Natalja, additional, Stander, Emily A, additional, Eymieux, Sébastien, additional, Burlaud-Gaillard, Julien, additional, Blanchard, Emmanuelle, additional, Clastre, Marc, additional, Atehortùa, Lucia, additional, St-Pierre, Benoit, additional, Giglioli-Guivarc’h, Nathalie, additional, Papon, Nicolas, additional, Nagegowda, Dinesh A, additional, O’Connor, Sarah E, additional, and Courdavault, Vincent, additional

Published
2020
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40. A plastid‐localized geranylgeranyl diphosphate synthase plays a necessary role in monoterpene indole alkaloid biosynthesis in

Author

Kumar, Sarma Rajeev, Rai, Avanish, Bomzan, Dikki Pedenla, Kumar, Krishna, Hemmerlin, Andrea, Dwivedi, Varun, Godbole, Rucha C., Barvkar, Vitthal, Shanker, Karuna, Shilpashree, H.B., Bhattacharya, Ankita, Smitha, Attibele Ramamurthy, Hegde, Namratha, Nagegowda, Dinesh A., Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
[SDV.BV]Life Sciences [q-bio]/Vegetal Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

47. A plastid‐localized bona fide geranylgeranyl diphosphate synthase plays a necessary role in monoterpene indole alkaloid biosynthesis in Catharanthus roseus

Author

Kumar, Sarma Rajeev, primary, Rai, Avanish, additional, Bomzan, Dikki Pedenla, additional, Kumar, Krishna, additional, Hemmerlin, Andréa, additional, Dwivedi, Varun, additional, Godbole, Rucha C., additional, Barvkar, Vitthal, additional, Shanker, Karuna, additional, Shilpashree, H. B., additional, Bhattacharya, Ankita, additional, Smitha, Attibele Ramamurthy, additional, Hegde, Namratha, additional, and Nagegowda, Dinesh A., additional

Published
2020
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48. Antibacterial efficacy of Jackfruit rag extract against clinically important pathogens and validation of its antimicrobial activity in Shigella dysenteriae infected Drosophila melanogaster infection model

Author

Dhwani, NV, primary, Raju, Gayathri, additional, Mathew, Sumi E, additional, Baranwal, Gaurav, additional, Shivaram, Shivakumar B, additional, Katiyar, Neeraj, additional, Pramanik, Nilkamal, additional, Jhunjhunwala, Siddharth, additional, Shilpashree, H.B., additional, Nagegowda, Dinesh A., additional, Kumar, Ritesh, additional, Shasany, Ajit K., additional, Biswas, Raja, additional, and Shankarappa, Sahadev A, additional

Published
2020
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50. Antibacterial efficacy of Jackfruit rag extract against clinically important pathogens and validation of its antimicrobial activity in Shigella dysenteriae infected Drosophila melanogaster infection model.

Author

Dhwani, N. V., Raju, Gayathri, Mathew, Sumi E., Baranwal, Gaurav, Shivaram, Shivakumar B., Katiyar, Neeraj, Pramanik, Nilkamal, Jhunjhunwala, Siddharth, Shilpashree, H. B., Nagegowda, Dinesh A., Kumar, Ritesh, Shasany, Ajit K., Biswas, Raja, and Shankarappa, Sahadev A.

Subjects
ANTIBACTERIAL agents, JACKFRUIT, PATHOGENIC microorganisms, DROSOPHILA melanogaster, GRAM-negative bacteria
Abstract

Exploration of alternative sources of antibacterial compounds is an important and possibly an effective solution to the current challenges in antimicrobial therapy. Plant derived wastes may offer one such alternative. Here, we investigated the antibacterial property of extract derived from a part of the Jackfruit (Artocarpus heterophyllus Lam.) called 'rag', generally considered as fruit waste. Morpho-physical characterization of the Jackfruit rag extract (JFRE) was performed using Gaschromatography, where peaks indicative of furfural; pentanoic acid; and hexadecanoic acid were observed. In vitro biocompatibility of JFRE was performed using the MTT assay, which showed comparable cellular viability between extracttreated and untreated mouse fibroblast cells. Agar well disc diffusion assay exhibited JFRE induced zones of inhibition for a wide variety of laboratory and clinical strains of Gram-positive and Gram-negative bacteria. Analysis of electron microscope images of bacterial cells suggests that JFRE induces cell death by disintegration of the bacterial cell wall and precipitating intracytoplasmic clumping. The antibacterial activity of the JFREs was further validated in vivo using Shigella dysenteriae infected fly model, where JFRE pre-fed flies infected with S. dysenteriae had significantly reduced mortality compared to controls. JFRE demonstrates broad antibacterial property, both in vitro and in vivo, possibly by its activity on bacterial cell wall. [ABSTRACT FROM AUTHOR]

Published
2021

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