Exploiting plant alkaloids

Schläger, Sabrina; Dräger, Birgit

doi:10.1016/j.copbio.2015.12.003

Cited by 79 publications

(38 citation statements)

References 48 publications

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“…Dopamine is an important neurotransmitter in the brain, and in plants, it is a precursor of numerous specialized metabolites, including phenethylisoquinoline alkaloids (e.g., colchicine) (Polturak and Aharoni 2018;Ehrenworth and Peralta-Yahya 2017), emetine alkaloids (e.g., emetine) (Nomura and Kutchan 2010), benzylisoquinoline alkaloids (e.g., morphine) (Schlager and Drager 2016;Liu et al 2017), catecholamines (e.g., epinephrine), and phenylethylamines (e.g., mescaline) (Rinner and Waser 2016). Dopamine can be synthesized via 3-hydroxylation of tyramine or decarboxylation of L-DOPA, but enzymes responsible for the 3-hydroxylation of tyrosine or tyramine are still unclear in plants.…”

Section: Biosynthesis Of Tyrosine-derived Specialized Metabolitesmentioning

confidence: 99%

General and specialized tyrosine metabolism pathways in plants

Fang

et al. 2019

aBIOTECH

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The tyrosine metabolism pathway serves as a starting point for the production of a variety of structurally diverse natural compounds in plants, such as tocopherols, plastoquinone, ubiquinone, betalains, salidroside, benzylisoquinoline alkaloids, and so on. Among these, tyrosine-derived metabolites, tocopherols, plastoquinone, and ubiquinone are essential to plant survival. In addition, this pathway provides us essential micronutrients (e.g., vitamin E and ubiquinone) and medicine (e.g., morphine, salidroside, and salvianolic acid B). However, our knowledge of the plant tyrosine metabolism pathway remains rudimentary, and genes encoding the pathway enzymes have not been fully defined. In this review, we summarize and discuss recent advances in the tyrosine metabolism pathway, key enzymes, and important tyrosine-derived metabolites in plants.

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Section: Biosynthesis Of Tyrosine-derived Specialized Metabolitesmentioning

confidence: 99%

General and specialized tyrosine metabolism pathways in plants

Fang

et al. 2019

aBIOTECH

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“…The chorismate is involved in the formation of both tryptophan and arogenate metabolites (Kumar et al, 2016b), the later one on the other hand, can be converted into tyrosine and phenylalanine, the branchpoints for the formation of alkaloids and phenylpropanoids, respectively (Pascual et al, 2016; Schlager and Drager, 2016). The CA formed from phenylalanine acts as immediate precursor to P-I and also produces various phenylpropanoids via the formation of p -CA (Kumar et al, 2016b; Rigano et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Modular Design of Picroside-II Biosynthesis Deciphered through NGS Transcriptomes and Metabolic Intermediates Analysis in Naturally Variant Chemotypes of a Medicinal Herb, Picrorhiza kurroa

2017

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Picroside-II (P-II), an iridoid glycoside, is used as an active ingredient of various commercial herbal formulations available for the treatment of liver ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing to its negligence in Picrorhiza kurroa shoots which sets constant barrier for function validation experiments. In this study, we utilized natural variation for P-II content in stolon tissues of different P. kurroa accessions and deciphered its metabolic route by integrating metabolomics of intermediates with differential NGS transcriptomes. Upon navigating through high vs. low P-II content accessions (1.3–2.6%), we have established that P-II is biosynthesized via degradation of ferulic acid (FA) to produce vanillic acid (VA) which acts as its immediate biosynthetic precursor. Moreover, the FA treatment in vitro at 150 μM concentration provided further confirmation with 2-fold rise in VA content. Interestingly, the cross-talk between different compartments of P. kurroa, i.e., shoots and stolons, resolved spatial complexity of P-II biosynthesis and consequently speculated the burgeoning necessity to bridge gap between VA and P-II production in P. kurroa shoots. This work thus, offers a forward looking strategy to produce both P-I and P-II in shoot cultures, a step toward providing a sustainable production platform for these medicinal compounds via-à-vis relieving pressure from natural habitat of P. kurroa.

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“…Vincristine is a naturally occurring alkaloid found in Catharanthus roseus and is mainly used to treat leukaemia and lymphomas . Its major side effect is progressive peripheral neuropathy.…”

Section: What Is Known and Objectivesmentioning

confidence: 99%

In vitro compatibility and stability of admixtures containing etoposide, epirubicin hydrochloride and vindesine sulphate in a single infusion bag

Yan

et al. 2019

J Clin Pharm Ther

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What is known and objectives: The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or refractory non-Hodgkin's lymphoma. However, vincristine and doxorubicin hydrochloride are relatively toxic, leading to neurovirulence and cardiotoxicity, respectively. In this study, we replaced these drugs with vindesine and epirubicin hydrochloride to reduce the cardiotoxicity and evaluated admixtures containing these drugs along with etoposide in a single infusion bag in vitro. Methods:The appearance and pH of the admixtures were evaluated, and the number of particles was detected. High-performance liquid chromatography was used to measure the concentration and degradation rates of etoposide, epirubicin hydrochloride and vindesine sulphate in each admixture. Results and discussion: No precipitation occurred when mixing clinically relevant concentrations of etoposide, epirubicin hydrochloride and vindesine sulphate in a 0.9% NaCl injection solution. Furthermore, the delta pH of the admixtures was ≤0.12 throughout the experiment, and the number of particles (≥10 and ≥25 μm) in the solutions over the 24 hours post-preparation period met USP standards. Etoposide, epirubicin hydrochloride and vindesine sulphate were retained at >96% of their initial concentrations in the admixtures at 25°C over the course of the experiment. Etoposide, epirubicin hydrochloride and vindesine sulphate are compatible when mixed in a 0.9% NaCl injection solution, and the admixtures are stable for at least 24 hours when stored in infusion bags. What is new and conclusion: This in vitro analysis indicates the suitability of our novel admixtures containing less toxic drug equivalents in a single infusion bag for clinical application. K E Y W O R D S admixture, compatibility, epirubicin hydrochloride, etoposide, stability, vindesine sulphate

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Exploiting plant alkaloids

Cited by 79 publications

References 48 publications

General and specialized tyrosine metabolism pathways in plants

General and specialized tyrosine metabolism pathways in plants

Modular Design of Picroside-II Biosynthesis Deciphered through NGS Transcriptomes and Metabolic Intermediates Analysis in Naturally Variant Chemotypes of a Medicinal Herb, Picrorhiza kurroa

In vitro compatibility and stability of admixtures containing etoposide, epirubicin hydrochloride and vindesine sulphate in a single infusion bag

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