Pharmacological Properties of Gelsemium Alkaloids

Gelsemium alkaloids are a diverse family of indole-based compounds derived from plants of the Gelsemium genus, notable for both potent therapeutic activities and significant toxicity. Their bioactivities span central nervous system modulation, analgesia, anxiolysis, anti-inflammatory and anticancer effects, underpinned by interactions with ligand-gated ion channels, signalling kinases and mitochondrial pathways. At low doses, specific alkaloids such as koumine and gelsemine exhibit neuroprotective and anxiolytic actions via modulation of glycine and GABA_A receptors, and may elevate neuroactive steroids in the spinal cord to relieve neuropathic pain. Anti-inflammatory properties arise from suppression of NF-κB and MAPK signalling, dampening cytokine release in immune cells. Antitumour potential has been demonstrated through induction of reactive oxygen species, mitochondrial dysfunction and apoptosis in cancer cell lines. The narrow margin between therapeutic and toxic doses remains a critical challenge, demanding precise understanding of pharmacokinetics, receptor selectivity and detoxification mechanisms. Ongoing research seeks to harness the structural diversity of these alkaloids for novel drug leads while minimising adverse effects.

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Pharmacological Properties of Gelsemium Alkaloids publication trend

The graph below shows the total number of articles in pharmacological properties of gelsemium alkaloids across all publications each year (not limited to Nature Index journals).

Technical terms

Indole alkaloid: An organic compound containing an indole core derived from tryptophan, often bioactive in the central nervous system.

Glycine receptor (GlyR): A pentameric ligand-gated chloride channel in the spinal cord and brainstem that mediates inhibitory neurotransmission.

GABA_A receptor: A ligand-gated ion channel that conducts chloride ions upon activation by γ-aminobutyric acid, the primary inhibitory neurotransmitter in the central nervous system.

NF-κB (nuclear factor kappa B): A transcription factor that regulates genes involved in inflammation, immunity and cell survival.

MAPK (mitogen-activated protein kinase): A family of serine/threonine kinases that transduce extracellular signals to intracellular responses, including inflammation and apoptosis.

IC₅₀: The concentration of a compound required to inhibit a biological process or receptor by 50%, used to compare potencies.

Apoptosis: Programmed cell death characterised by caspase activation, mitochondrial membrane potential loss and DNA fragmentation.

References

1. Molecular Pharmacology of Gelsemium Alkaloids on Inhibitory Receptors. International Journal of Molecular Sciences (2024).
2. Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium: a comprehensive review. Journal of Enzyme Inhibition and Medicinal Chemistry (2023).
3. Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans. Molecules (2023).
4. Koumine Attenuates Lipopolysaccaride-Stimulated Inflammation in RAW264.7 Macrophages, Coincidentally Associated with Inhibition of NF-κB, ERK and p38 Pathways. International Journal of Molecular Sciences (2016).
5. Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling. Biomolecules (2019).
6. Koumine Enhances Spinal Cord 3α-Hydroxysteroid Oxidoreductase Expression and Activity in a Rat Model of Neuropathic Pain. Molecular Pain (2015).