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Mariana Sottomayor - One of the best experts on this subject based on the ideXlab platform.

  • synergistic and additive influence of cyclodextrins and methyl jasmonate on the expression of the terpenoid indole alkaloid pathway genes and metabolites in catharanthus roseus cell cultures
    Plant Cell Tissue and Organ Culture, 2014
    Co-Authors: Jorge Gutierrez, Lorena Almagro, M A Pedreno, Mariana Sottomayor
    Abstract:

    In the present work, we study the relationship between the production of indole alkaloids and the transcript profiles of several genes involved in their biosynthesis in Catharanthus roseus cell cultures elicited with 50 mM cyclodextrins (CDs) and/or 100 µM methyl jasmonate (MJ) for 8 days. Gene expression and indole alkaloid production were significantly enhanced by CDs treatment while MJ induced alkaloid synthesis to a lesser extent and had almost no effect on gene expression. The combined treatment with both the elicitors pointed to synergistic effect on gene transcript accumulation, which resulted in a 6,071.42 and 8,100 % enhancement of ajmalicine and Catharanthine productivity, respectively, compared with non-treated cells at day 8. This increase in alkaloid production under the combined influence of CDs and MJ was 329.66 and 595.07 % for ajmalicine and 202.5 and 291.36 % more for Catharanthine in compared with elicitation with CDs or MJ alone. Interestingly the over-synthesized alkaloids readily secreted into the culture medium, thereby avoiding the possibility of retro-inhibition and cytotoxicity due to their accumulation in cells.

  • pharmacological effects of catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission
    Phytomedicine, 2010
    Co-Authors: David M Pereira, Mariana Sottomayor, Federico Ferreres, Patricia Valentao, Jorge M A Oliveira, Joana Faria, Luis Gaspar, Paula B Andrade
    Abstract:

    The leaves of Catharanthus roseus constitute the only source of the well known indolomonoterpenic alkaloids vincristine and vinblastine. In this work we studied the biological potential of the roots, which are used in several countries as decocts or hot water extracts for the treatment of a number of conditions. The aqueous extract strongly inhibited acetylcholinesterase (AchE) in an in vitro microassay, an effect ascribable mainly to serpentine (IC(50) = 0.775 microM vs physostigmine IC(50) = 6.45 microM) as assessed with the pure compound. Pure alkaloids were tested for muscarinic and nicotinic antagonism using rat ex-vivo preparations, namely, ileum and diaphragm/phrenic-nerve, respectively. Serpentine competitively blocked muscarinic receptors with a pA(2) of 5.2, whereas the precursor ajmalicine up to 80 microM was undistinguishable from control, and Catharanthine exhibited an unsurmountable muscarinic antagonism at greater than 10 microM concentrations. Nicotinic receptor mediated diaphragm contractions were fully inhibited by Catharanthine (IC(50) = 59.6 microM) and ajmalicine (IC(50) = 72.3 microM), in a reversible but non-competitive manner, unlike the more potent nicotinic antagonist tubocurarine (IC(50) = 0.35 microM) whose competitive blockade was overcome by a physostigmine-induced increase in acetylcholine. Serpentine up to 100 microM did not change diaphragm contractions suggesting reduced affinity for neuromuscular nicotinic receptors. Despite strong in vitro AchE inhibition, serpentine failed to restore diaphragm contractions upon submaximal tubocurarine blockade, suggesting that poor tissue penetration may prevent serpentine from inhibiting AchE in deep neuromuscular synapses in the ex-vivo preparation. To our knowledge, the present study is the first to assess the effect of C. roseus root extracts, as well as of serpentine, ajmalicine and Catharanthine on AchE. The results described herein suggest that the currently overlooked C. roseus roots may constitute a promising source of compounds with pharmaceutical interest. Moreover, given serpentine's potent in vitro AchE inhibitory activity and low cholinergic receptor affinity, it is conceivable that minor structural modifications may yield a potent and selective AchE inhibitor, potentially useful for the pharmacological management of conditions such as Alzheimer's disease and/or myasthenia gravis.

  • simple and reproducible hplc dad esi ms ms analysis of alkaloids in catharanthus roseus roots
    Journal of Pharmaceutical and Biomedical Analysis, 2010
    Co-Authors: Federico Ferreres, Mariana Sottomayor, David M Pereira, Patricia Valentao, Jorge M A Oliveira, Joana Faria, Luis Gaspar, Paula B Andrade
    Abstract:

    Abstract Catharanthus roseus is one of the most important medicinal plants worldwide. The leaves of this species are the only source of the indolomonoterpenic alkaloids vincristin (leurocristine) and vinblastin (vincaleucoblastine), whose anticancer activity represents powerful therapeutics to many diseases, such as Hodgkin lymphoma. Usually, the remaining plant parts go to waste. Here we describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied using HPLC–DAD–ESI-MS/MS, which allowed the identification of 19- S -vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, Catharanthine, serpentine and a serpentine isomer. Quantification of the identified compounds revealed that serpentine and its isomer were predominant (64.7%) over the other alkaloids, namely vindolinine and its isomer (23.9%), Catharanthine (7.7%) and ajmalicine (3.8%). The used procedure revealed to be simple, sensitive and reproducible.

  • on the fate of Catharanthine and vindoline during the peroxidase mediated enzymatic synthesis of α 3 4 anhydrovinblastine
    Enzyme and Microbial Technology, 1997
    Co-Authors: Mariana Sottomayor, Frank Dicosmo, Ros A Barcelo
    Abstract:

    The fate of Catharanthine and vindoline during the peroxidase-mediated enzymatic synthesis of α-3′,4′-anhydrovinblastine (AVLB) has been studied. The results showed that Catharanthine and vindoline are suitable electron donors for the oxidizing intermediates of horseradish peroxidase (compound I and compound II). The reduction of peroxidase compound II is one of the limiting steps in the coupling reaction. In fact, k3 (compound II reduction constant) values were 2.53 × 103 m−1 s−1 and 3.57 × 103 m−1 s−1 for Catharanthine and vindoline, respectively. These values are extremely low if we compare them with those found for other substrates of peroxidase-catalyzed oxidations. From these results and the analysis of the reaction products in conditions in which coupling occurred, we propose a mechanism where vindoline-free radicals resulting from reaction of vindoline with the oxidized states of peroxidase are deactivated by reaction with Catharanthine. Catharanthine radicals actually set off the coupling reaction.

Paula B Andrade - One of the best experts on this subject based on the ideXlab platform.

  • pharmacological effects of catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission
    Phytomedicine, 2010
    Co-Authors: David M Pereira, Mariana Sottomayor, Federico Ferreres, Patricia Valentao, Jorge M A Oliveira, Joana Faria, Luis Gaspar, Paula B Andrade
    Abstract:

    The leaves of Catharanthus roseus constitute the only source of the well known indolomonoterpenic alkaloids vincristine and vinblastine. In this work we studied the biological potential of the roots, which are used in several countries as decocts or hot water extracts for the treatment of a number of conditions. The aqueous extract strongly inhibited acetylcholinesterase (AchE) in an in vitro microassay, an effect ascribable mainly to serpentine (IC(50) = 0.775 microM vs physostigmine IC(50) = 6.45 microM) as assessed with the pure compound. Pure alkaloids were tested for muscarinic and nicotinic antagonism using rat ex-vivo preparations, namely, ileum and diaphragm/phrenic-nerve, respectively. Serpentine competitively blocked muscarinic receptors with a pA(2) of 5.2, whereas the precursor ajmalicine up to 80 microM was undistinguishable from control, and Catharanthine exhibited an unsurmountable muscarinic antagonism at greater than 10 microM concentrations. Nicotinic receptor mediated diaphragm contractions were fully inhibited by Catharanthine (IC(50) = 59.6 microM) and ajmalicine (IC(50) = 72.3 microM), in a reversible but non-competitive manner, unlike the more potent nicotinic antagonist tubocurarine (IC(50) = 0.35 microM) whose competitive blockade was overcome by a physostigmine-induced increase in acetylcholine. Serpentine up to 100 microM did not change diaphragm contractions suggesting reduced affinity for neuromuscular nicotinic receptors. Despite strong in vitro AchE inhibition, serpentine failed to restore diaphragm contractions upon submaximal tubocurarine blockade, suggesting that poor tissue penetration may prevent serpentine from inhibiting AchE in deep neuromuscular synapses in the ex-vivo preparation. To our knowledge, the present study is the first to assess the effect of C. roseus root extracts, as well as of serpentine, ajmalicine and Catharanthine on AchE. The results described herein suggest that the currently overlooked C. roseus roots may constitute a promising source of compounds with pharmaceutical interest. Moreover, given serpentine's potent in vitro AchE inhibitory activity and low cholinergic receptor affinity, it is conceivable that minor structural modifications may yield a potent and selective AchE inhibitor, potentially useful for the pharmacological management of conditions such as Alzheimer's disease and/or myasthenia gravis.

  • simple and reproducible hplc dad esi ms ms analysis of alkaloids in catharanthus roseus roots
    Journal of Pharmaceutical and Biomedical Analysis, 2010
    Co-Authors: Federico Ferreres, Mariana Sottomayor, David M Pereira, Patricia Valentao, Jorge M A Oliveira, Joana Faria, Luis Gaspar, Paula B Andrade
    Abstract:

    Abstract Catharanthus roseus is one of the most important medicinal plants worldwide. The leaves of this species are the only source of the indolomonoterpenic alkaloids vincristin (leurocristine) and vinblastin (vincaleucoblastine), whose anticancer activity represents powerful therapeutics to many diseases, such as Hodgkin lymphoma. Usually, the remaining plant parts go to waste. Here we describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied using HPLC–DAD–ESI-MS/MS, which allowed the identification of 19- S -vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, Catharanthine, serpentine and a serpentine isomer. Quantification of the identified compounds revealed that serpentine and its isomer were predominant (64.7%) over the other alkaloids, namely vindolinine and its isomer (23.9%), Catharanthine (7.7%) and ajmalicine (3.8%). The used procedure revealed to be simple, sensitive and reproducible.

Nelson Nainggolan - One of the best experts on this subject based on the ideXlab platform.

Jayabaskaran Chelliah - One of the best experts on this subject based on the ideXlab platform.

Shilpa Ramani - One of the best experts on this subject based on the ideXlab platform.