Beyond Alkaloids: Novel Bioactive Natural Products From Lobelia Species

Zheng, Qi; Wang, Ye; Zhang, Shuihan

doi:10.3389/fphar.2021.638210

Cited by 10 publications

(11 citation statements)

References 68 publications

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“…Numerous investigations have shown that lobeline has a variety of pharmacological effects on the CNS (reviewed in Reference 46). Interestingly, lobeline shares 73% structural similarity and several common pharmacophoric features like aromatic rings, an ionizable moiety and a hydrophobic surface with donepezil, a well‐known AChE inhibitor (Figure 1a–d and Table 1).…”

Section: Resultsmentioning

confidence: 99%

Lobeline: A multifunctional alkaloid modulates cholinergic and glutamatergic activities

et al. 2023

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Developing drugs for Alzheimer's disease (AD) is an extremely challenging task due to its devastating pathology. Previous studies have indicated that natural compounds play a crucial role as lead molecules in the development of drugs. Even though, there are remarkable technological advancements in the isolation and synthesis of natural compounds, the targets for many of them are still unknown. In the present study, lobeline, a piperidine alkaloid has been identified as a cholinesterase inhibitor through chemical similarity assisted target fishing method. The structural similarities between lobeline and donepezil, a known acetylcholinesterase (AChE) inhibitor encouraged us to hypothesize that lobeline may also exhibit AChE inhibitory properties. It was further confirmed by in silico, in vitro and biophysical studies that lobeline could inhibit cholinesterase. The binding profiles indicated that lobeline has a higher affinity for AChE than BChE. Since excitotoxicity is one of the major pathological events associated with AD progression, we also investigated the neuroprotective potential of lobeline against glutamate mediated excitotoxicity in rat primary cortical neurons. The cell based NMDA receptor (NMDAR) assay with lobeline suggested that neuroprotective potential of lobeline is mediated through the blockade of NMDAR activity.

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Section: Resultsmentioning

confidence: 99%

Lobeline: A multifunctional alkaloid modulates cholinergic and glutamatergic activities

et al. 2023

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“…First, the proper mechanism by which pH induced isomerization should be revealed. Secondly, the study of isomer activity should not be limited to nAChRs receptors, nor should it be restricted to the excitatory respiration effect [ 26 ]. Last but not the least, the study of the structure–activity relationship of trans -lobeline should be considered in subsequent studies.…”

Section: Discussionmentioning

confidence: 99%

From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors

Yang

Tang

et al. 2022

Molecules

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Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

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“…East Asian lobelias are traditional medicinal plant species because of their bioactivity and many chemical constituents (Anand et al, 2009;Han et al, 2013;Zheng et al, 2021). However, the scarcity of genomic resources for East Asian lobelias has hampered plant genetics, ecology, taxonomy, and resource utilization.…”

Section: Molecular Markersmentioning

confidence: 99%

“…Valuable medicines with anti-inflammatory, antioxidative, antiviral, and antiepileptic functions can be made from lobeline and its derivatives (Tamboli et al, 2012;Thawabteh et al, 2019). Lobeline is predominantly derived from plants of the Lobelia (Lammers, 2007b;Zheng et al, 2021). Lobelia L. is the largest genus among all the 29 genera in the subfamily Lobelioideae (Campanulaceae) and has an almost cosmopolitan distribution mainly in tropical to warm-temperate climate regions (Lammers, 2007a;Lammers, 2011).…”

Section: Introductionmentioning

confidence: 99%

Plastome evolution in the East Asian lobelias (Lobelioideae) using phylogenomic and comparative analyses

Xie

Liu

et al. 2023

Front. Plant Sci.

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Lobelia species, as rich source of the alkaloid lobeline which has been shown to have important biological activity, have been used in folk medicine throughout East Asia to treat various diseases. However, Lobelia is a complex and varied genus in East Asia and is thus difficult to identify. Genomic resources would aid identification, however the availability of such information is poor, preventing a clear understanding of their evolutionary history from being established. To close this gap in the available genomic data, in this study, 17 plastomes of East Asian lobelias were newly sequenced and assembled. Although the plastomes of Lobelia sect. Hypsela, L. sect. Speirema, and L. sect. Rhynchopetalum shared the gene structure, the inverted repeat (IR)/large single copy (LSC) boundaries, genome size, and the number of repeats were variable, indicating the non-conservative nature of plastome evolution within these sections. However, the genomes of the Lobelia sect. Delostemon and L. sect. Stenotium showed rearrangements, revealing that these two sections might have undergone different evolutionary histories. We assessed nine hotspot genes and 27-51 simple sequence repeat motifs, which will also serve as valuable DNA barcode regions in future population genetics studies and for the delineation of plant species. Our phylogenetic analysis resolved the evolutionary positions of the five sections in agreement with previous evolutionary trees based on morphological features. Although phylogenetic reconstruction of Lobelioideae based on the rpoC2 gene has rarely been performed, our results indicated that it contains a considerable amount of phylogenetic information and offers great promise for further phylogenetic analysis of Lobelioideae. Our site-specific model identified 173 sites under highly positive selections. The branch-site model exhibited 11 positive selection sites involving four genes in the East Asian branches. These four genes may play critical roles in the adaptation of East Asian taxa to diverse environments. Our study is the first to detect plastome organization, phylogenetic utility, and signatures of positive selection in the plastomes of East Asian lobelias, which will help to further advance taxonomic and evolutionary studies and the utilization of medicinal plant resources.

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Beyond Alkaloids: Novel Bioactive Natural Products From Lobelia Species

Cited by 10 publications

References 68 publications

Lobeline: A multifunctional alkaloid modulates cholinergic and glutamatergic activities

Lobeline: A multifunctional alkaloid modulates cholinergic and glutamatergic activities

From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors

Plastome evolution in the East Asian lobelias (Lobelioideae) using phylogenomic and comparative analyses

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