Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice

Chen, Liping; Pan, Hanbo; Bai, Yujing; Li, Huiqin; Yang, Wen; Lin, Zhi‐Xiu; Cui, Wei; Xian, Yan‐Fang

doi:10.1007/s00213-020-05522-y

Cited by 21 publications

(11 citation statements)

References 42 publications

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“…Neurodegeneration is used for several neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. There are various pathophysiological bases of neurodegenerative diseases but the most important are: accumulation of abnormal proteins, oxidative stress, neuroinflammation, and mitochondrial dysfunction [ 4 , 5 ], in Figure 1 , a simple diagram has shown the progression of neurodegenerative diseases, and the role of different factors.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

et al. 2020

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Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.

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Section: Introductionmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

et al. 2020

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“…Exogenous IL-17 administration may increase the activity of the transient receptor protein vanilloid 4 (TRPV4) ( Hung et al, 2017 ), which was discovered in network pharmacology. Furthermore, gelsemine and koumine have been shown to inhibit the overexpression of pro-inflammatory cytokines in mice and rats ( Jin et al, 2018b ; Chen et al, 2020 ). These above evidenced improve our confidence that GEB can restore the imbalance between pro-inflammatory cytokines and anti-inflammatory cytokines and thus promote its antinociceptive effects.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Gelsemium elegans (Gardner and Champ.) Benth. Against Neuropathic Pain Based on Network Pharmacology and Experimental Evidence

Que

Chen

et al. 2022

Front. Pharmacol.

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Gelsemium elegans (Gardner and Champ.) Benth. (Gelsemiaceae) (GEB) is a toxic plant indigenous to Southeast Asia especially China, and has long been used as Chinese folk medicine for the treatment of various types of pain, including neuropathic pain (NPP). Nevertheless, limited data are available on the understanding of the interactions between ingredients-targets-pathways. The present study integrated network pharmacology and experimental evidence to decipher molecular mechanisms of GEB against NPP. The candidate ingredients of GEB were collected from the published literature and online databases. Potentially active targets of GEB were predicted using the SwissTargetPrediction database. NPP-associated targets were retrieved from GeneCards, Therapeutic Target database, and DrugBank. Then the protein-protein interaction network was constructed. The DAVID database was applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Molecular docking was employed to validate the interaction between ingredients and targets. Subsequently, a 50 ns molecular dynamics simulation was performed to analyze the conformational stability of the protein-ligand complex. Furthermore, the potential anti-NPP mechanisms of GEB were evaluated in the rat chronic constriction injury model. A total of 47 alkaloids and 52 core targets were successfully identified for GEB in the treatment of NPP. Functional enrichment analysis showed that GEB was mainly involved in phosphorylation reactions and nitric oxide synthesis processes. It also participated in 73 pathways in the pathogenesis of NPP, including the neuroactive ligand-receptor interaction signaling pathway, calcium signaling pathway, and MAPK signaling pathway. Interestingly, 11-Hydroxyrankinidin well matched the active pockets of crucial targets, such as EGFR, JAK1, and AKT1. The 11-hydroxyrankinidin-EGFR complex was stable throughout the entire molecular dynamics simulation. Besides, the expression of EGFR and JAK1 could be regulated by koumine to achieve the anti-NPP action. These findings revealed the complex network relationship of GEB in the “multi-ingredient, multi-target, multi-pathway” mode, and explained the synergistic regulatory effect of each complex ingredient of GEB based on the holistic view of traditional Chinese medicine. The present study would provide a scientific approach and strategy for further studies of GEB in the treatment of NPP in the future.

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“…Its mechanisms may not only increase the levels of neurosteroid pregnenolone and allopregnanolone in the hippocampus [ 31 ], but can also be related to the agonistic effect on glycine receptors [ 32 ]. A low concentration (5–10 µg/kg) of koumine significantly alleviates the cognitive impairment induced by beta amyloid (main neurotoxin of Alzheimer’s disease [AD]), suggesting that koumine inhibits the proliferation of glial cells associated with AD [ 33 ]. Koumine inhibits the overexpression of interleukin 6 (IL-6), IL-1, and tumor necrosis factor (TNF) in tumors, showing anti-neuritis effects [ 34 ].…”

Section: Pharmacological Effects Of Gebmentioning

confidence: 99%

“…These findings lay a certain foundation for the treatment of AD and related neurodegenerative diseases. It is reasonably deduced that koumine inhibits glycogen synthase kinase-3 (GSK3) (activity of GSK3 increases in the brain of AD patients, and GSK3 is a strong promoter of pro-inflammatory cytokines), thereby reducing GSK3-mediated neuroinflammation [ 33 ].…”

Section: Pharmacological Effects Of Gebmentioning

confidence: 99%

Gelsemium elegans Benth: Chemical Components, Pharmacological Effects, and Toxicity Mechanisms

et al. 2021

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Gelsemium elegans Benth (GEB), also known as heartbreak grass, is a highly poisonous plant belonging to the family Loganiaceae and genus Gelsemium that has broad application prospects in medicine. This article reviews its chemical components, pharmacological effects, toxicity mechanisms, and research progress in clinical applications in recent years. Indole alkaloids are the main active components of GEB and have a variety of pharmacological and biological functions. They have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the therapeutic dose being close to the toxic dose. Application of small-dose indole alkaloids fails to work effectively, while high-dose usage is prone to poisoning, aggravating the patient’s conditions. Special caution is needed, especially to observe the changes in the disease condition of the patients in clinical practice. In-depth research on the chemical components and mechanisms of GEB is essential to the development of promising lead compounds and lays the foundation for extensive clinical application and safe usage of GEB in the future.

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Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice

Cited by 21 publications

References 42 publications

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

Molecular Mechanism of Gelsemium elegans (Gardner and Champ.) Benth. Against Neuropathic Pain Based on Network Pharmacology and Experimental Evidence

Gelsemium elegans Benth: Chemical Components, Pharmacological Effects, and Toxicity Mechanisms

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