Quinolizidine-Type Alkaloids: Chemodiversity, Occurrence, and Bioactivity

Cely-Veloza, W; Kato, Massuo Jorge; Coy-Barrera, Ericsson

doi:10.1021/acsomega.3c02179

Cited by 14 publications

(5 citation statements)

References 278 publications

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“…4d). Our results confirm the intermediacy of (−)-sparteine in relation to (+)-lupanine and its derivatives, which has not been clear in recent depictions of the general QA pathway 32, 33 .…”

Section: Mainsupporting

confidence: 84%

Metabolic engineering of narrow-leafed lupin for the production of enantiomerically pure (‒)-sparteine

Mancinotti,

Yang,

Geu-Flores

2024

Preprint

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Sparteine is a plant-derived alkaloid widely known for its utility as chiral ligand in asymmetric synthesis. However, its variable market price and availability have failed to meet the demand for a cheap and reliable product. Sparteine is naturally synthesized by a sub-group of legume plants, which typically accumulate complex mixtures of closely related alkaloids. Here, we identified two enzymes from narrow-leafed lupin (NLL, L. angustifolius) that can sequentially oxidize (−)-sparteine to (+)-lupanine. The first enzyme is a cytochrome P450 monooxygenase belonging to family 71 (CYP71D189) and the second one is a short-chain dehydrogenase/reductase (SDR1). We also screened a non-GMO NLL mutant library and isolated a knockout in CYP71D189. The knockout displayed an altered metabolic profile where (−)-sparteine accounted for 96% of the alkaloid content in the seeds (GC-MS basis). The (−)-sparteine isolated from the mutant seeds was enantiomerically pure (99% ee). Apart from the altered alkaloid profile, the mutant did not have any noticeable phenotype. Our work demonstrates that (−)-sparteine is the precursor of most QAs in NLL and provides a convenient source of this valuable compound for academia and industry.

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Section: Mainsupporting

confidence: 84%

Metabolic engineering of narrow-leafed lupin for the production of enantiomerically pure (‒)-sparteine

Mancinotti,

Yang,

Geu-Flores

2024

Preprint

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“…Oxymatrine is a quinolizidine alkaloid compound that has been shown in numerous studies to have various beneficiary functions, including antioxidant effects; antiinflammatory, antiviral, and anticancer activities; immune system regulation; cardiovascular improvement; and nervous system protection [33][34][35][36][37]. It can activate the Nrf2 pathway and enhance antioxidant enzymes [39,40]. Several studies have reported that OM treatment could improve ischemia/reperfusion and liver failure through the Nrf2/ho-1 pathway [30,31,41].…”

Section: Discussionmentioning

confidence: 99%

Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase

Maharajan,

Lee,

Vijayakumar

et al. 2023

Antioxidants

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The accumulation of oxidative stress is one of the important factors causing cellular senescence. Oxymatrine (OM) is a natural quinolizidine alkaloid compound known for its antioxidant effects. This study aimed to investigate the anti-senescence potential of OM through oxidative stress-induced in vitro and in vivo models. By treating 600 μM of H2O2 to the HT22 mouse hippocampal neuronal cell line and by administering 150 mg/kg D-galactose to mice, we generated oxidative stress-induced senescence models. After providing 1, 2, and 4 μg/mL of OM to the HT22 mouse cell line and by administering 50 mg/kg OM to mice, we evaluated the enhancing effects. We evaluated different senescence markers, AMPK activity, and autophagy, along with DCFH-DA detection reaction and behavioral tests. In HT22 cells, OM showed a protective effect. OM, by reducing ROS and increasing p-AMPK expression, could potentially reduce oxidative stress-induced senescence. In the D-Gal-induced senescence mouse model, both the brain and heart tissues recovered AMPK activity, resulting in reduced levels of senescence. In neural tissue, to assess neurological recovery, including anxiety symptoms and exploration, we used a behavioral test. We also found that OM decreased the expression level of receptors for advanced glycation end products (RAGE). In heart tissue, we could observe the restoration of AMPK activity, which also increased the activity of autophagy. The results of our study suggest that OM ameliorates oxidative stress-induced senescence through its antioxidant action by restoring AMPK activity.

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“…Sophora alopecuroides L. (Fabaceae family, Sophora genus) is widely distributed over a large area of northwestern China and southern Russia. , This plant has long been used in heart disease, treating fever, bacterial infection, rheumatism, and gastrointestinal diseases in traditional Chinese medicine. − Phytochemical investigations have shown that S. alopecuroides contains quinolizidine alkaloids (QAs, matrine-, cytisine-, anagyrine-, thermopsine-, and aloperine-types), flavonoids, polysaccharides, and steroids. ,− Among these compounds, aloperine, which was first isolated in 1935 from the leaves and seeds of S. alopecuroides, , has been extensively researched and has displayed good bioactivity.…”

Section: Introductionmentioning

confidence: 99%

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of Sophora alopecuroides L.

Hu,

Zhang,

Zhang

et al. 2024

J. Agric. Food Chem.

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As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1−15) as well as six known aloperine-type alkaloids (16−21) were obtained from the extract of S. alopecuroides. The structures of 1−21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1−21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1−21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC 50 : 7.38 μg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.

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Quinolizidine-Type Alkaloids: Chemodiversity, Occurrence, and Bioactivity

Cited by 14 publications

References 278 publications

Metabolic engineering of narrow-leafed lupin for the production of enantiomerically pure (‒)-sparteine

Metabolic engineering of narrow-leafed lupin for the production of enantiomerically pure (‒)-sparteine

Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of Sophora alopecuroides L.

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