Gelsemine free base

• CAS: 509-15-9
• Catalog Number: ACM509159
• Category: Main Products
• Molecular Weight: 322.40
• Molecular Formula: C₂₀H₂₂N₂O₂
• Synonyms: 8abeta,9s*,10s*))-8alph; Gelsemin; GESEMINE; gelsemine free base; GELSAMINE
• IUPAC Name: GELSEMINE
• SMILES: CN1CC2(C3CC4C5(C2C1C3CO4)C6=CC=CC=C6NC5=O)C=C
• InChI Key: NFYYATWFXNPTRM-UHFFFAOYSA-N
• Boiling Point: 493.4ºC at 760 mmHg
• Melting Point: 181-183ºC
• Flash Point: 252.2ºC
• Density: 1.33 g/cm³
• Appearance: White powder
• EC Number: 208-095-2
• Exact Mass: 322.16800
• Packing Group: I
• WGK Germany: 3

Case Study

Anti-Mechanical Allodynia, Glycine Receptor-Activating and Neurosteroid-Mediated Antinociceptive Properties of Gelsemine

Shoaib, R. M., Zhang, J. Y., Mao, X. F., & Wang, Y. X. Biochemical Pharmacology, 2019, 165, 129-140.

The pharmacological properties and molecular mechanism of gelsemine (a principal indole alkaloid isolated from Gelsemium sempervirens Ait.) were studied using in vivo neuropathic pain models, radioligand binding assays, and spinal molecular analyses. The main bioactive component is gelsemine, with indole alkaloid structure as the core functional moiety responsible for its anti-mechanical allodynia, glycine receptor-activating, and neurosteroid-mediated antinociceptive effects.
Gelsemine exhibited significant anti-mechanical allodynia activity: in L5/L6 spinal nerve-ligated neuropathic rats, intrathecal injection of gelsemine (10 μg) produced potent mechanical antiallodynia, with an ED₅₀ of 0.5 μg and maximum effect of 51% MPE, effectively elevating paw withdrawal thresholds in the injured hindlimb. It demonstrated potent glycine receptor-activating effects: gelsemine acted as a full orthosteric agonist, competitively displacing ³H‑strychnine binding to spinal glycine receptors (IC₅₀ = 43.8 μM) and activating spinal α3‑glycine receptors without affecting glial activity. Additionally, gelsemine exerted neurosteroid-mediated antinociceptive properties: it concentration‑dependently upregulated 3α‑hydroxysteroid oxidoreductase (3α‑HSOR) mRNA in spinal neurons by 68%, promoted allopregnanolone biosynthesis, and enhanced GABAₐ receptor‑mediated inhibition. Molecular and behavioral analyses confirmed complete blockade of antiallodynia by strychnine, 3α‑HSOR inhibition, siRNA gene silencing, or GABAₐ receptor antagonism, with no effect from minocycline. These studies demonstrate that gelsemine possesses significant anti-mechanical allodynia, glycine receptor-activating and neurosteroid-mediated antinociceptive properties.
The in vivo antiallodynic effect was investigated in male Wistar rats with L5/L6 spinal nerve ligation-induced neuropathy, randomized into seven groups (n = 5-6 per group): normal, sham, neuropathic control, vehicle, gelsemine (10 μg), gelsemine + strychnine, and gelsemine + medroxyprogesterone acetate. Intrathecal drugs were administered at designated time points; mechanical withdrawal thresholds were measured via von Frey filaments. Spinal 3α‑HSOR mRNA was quantified by RT‑qPCR; radioligand binding assays characterized glycine receptor interactions. The results verified that gelsemine produces robust mechanical antiallodynia through the spinal neuronal glycine receptor/3α‑HSOR/allopregnanolone/GABAₐ receptor pathway.

Anxiolytic, Neurosteroid-Modulating and Non-Sedative Properties of Gelsemine

Meyer, L., Boujedaini, N., Patte‑Mensah, C., & Mensah‑Nyagan, A. G. Behavioural Brain Research, 2013, 253, 90-94.

Gelsemine exhibited significant anxiolytic activity: in adult male Sprague‑Dawley rats, daily intraperitoneal injection of gelsemine (10⁻⁶ to 10⁻¹⁰ M) for 7 days dose‑dependently increased open‑arm entries by up to 58% and open‑arm time by up to 99%, comparable to diazepam (1.25 mg/kg). It demonstrated potent anxiety‑relieving effects: it reduced protected stretched attend postures by 23-36%, a specific ethological marker of anxiety, without altering locomotor activity or rearing behavior. Additionally, gelsemine exerted non‑sedative properties: closed‑arm entries and general exploratory activity remained unchanged across all doses, indicating selective anxiolysis without motor impairment. Behavioral analyses confirmed robust, dose‑dependent anxiolysis with no sedative side effects, supporting safe therapeutic use. These studies demonstrate that gelsemine possesses significant anxiolytic, neurosteroid‑modulating and non‑sedative properties.
The in vivo anxiolytic effect was investigated in 84 adult male Sprague‑Dawley rats randomized into seven groups (n = 12 per group): naive control, vehicle control, diazepam (1.25 mg/kg), and three gelsemine doses (10⁻⁶, 10⁻¹⁰, 10⁻¹⁴ M). Drugs were administered daily for 7 days; anxiety‑related behaviors were scored via automated video tracking in the elevated plus‑maze. Outcomes included open‑arm entries, open‑arm time, protected stretched postures, closed‑arm entries, and rearing frequency. The results verified that low‑dose gelsemine produces safe, selective anxiolysis likely mediated by enhanced allopregnanolone biosynthesis in limbic brain regions.

Neurosteroid-Synthesizing, Glycine Receptor-Activating and Central-Modulating Properties of Gelsemine

Venard, C., Boujedaini, N., Mensah-Nyagan, A. G., & Patte-Mensah, C. Evidence-Based Complementary and Alternative Medicine, 2011, 407617.

Gelsemine exhibited significant neurosteroid-synthesizing activity: at 5 cH dilution, gelsemine increased the production of allopregnanolone (3α,5α-THP) by 193% in spinal cord slices and 94% in limbic system (hippocampus + amygdala) slices, with 100% reproducibility. It demonstrated potent glycine receptor-activating effects: the stimulatory action on allopregnanolone biosynthesis was fully blocked by strychnine (10⁻⁵-10⁻⁶ M), a selective glycine receptor antagonist, confirming glycine receptor dependence. Additionally, gelsemine exerted graded central-modulating properties: 9 cH dilution showed partial activity (75% reproducibility), while 15 cH was inactive, indicating a dilution‑dependent biological effect. Biochemical analyses confirmed enhanced conversion of [³H]‑progesterone to [³H]‑3α,5α‑THP via upregulated 3α‑hydroxysteroid oxidoreductase activity. These studies demonstrate that gelsemine possesses significant neurosteroid-synthesizing, glycine receptor-activating and central-modulating properties.
The in vitro neuroactive effect was investigated in spinal cord and limbic system slices from adult male Sprague‑Dawley rats. Experimental groups included control, gelsemine 5 cH, 9 cH, 15 cH, and co‑treatment with strychnine. [³H]‑progesterone conversion to [³H]‑allopregnanolone was quantified by HPLC‑flow scintillation counting. Data were analyzed by ANOVA with Bonferroni's test. The results verified that gelsemine stimulates neurosteroid biosynthesis in spinal and limbic regions through glycine receptor activation, supporting its anxiolytic and analgesic mechanisms.

Anti-Anxiety, Glycine Receptor-Agonist and Neuroinflammatory-Inhibitory Properties of Gelsemine

Long, J. Y., Tang, M. H., Zuo, M. T., Xu, W. B., Meng, S. Y., & Liu, Z. Y. Brain-X, 2023, 1, e46.

Gelsemine exhibited significant anti-anxiety activity: in CUMS-induced anxious mice, intraperitoneal administration of gelsemine markedly increased open‑arm entries and open‑arm residence time in the elevated plus‑maze test, while raising central exploration time in the open‑field test, without altering locomotor activity. It demonstrated potent glycine receptor‑agonist effects: as a full orthosteric agonist of glycine receptors (GlyR), it enhanced chloride influx, reduced neuronal excitability, and upregulated 3α‑hydroxysteroid oxidoreductase (3α‑HSOR) to promote allopregnanolone biosynthesis, thereby potentiating GABAₐ receptor‑mediated inhibitory transmission. Additionally, gelsemine exerted neuroinflammatory‑inhibitory properties: it suppressed NLRP3 inflammasome overexpression in the hypothalamus, reduced IL‑1β and IL‑6 release, and downregulated excessive hypothalamic BDNF and CREB to restore neural plasticity. Behavioral and molecular analyses confirmed restored HPA‑axis homeostasis, reduced inflammatory infiltration, and normalized anxiety‑related behaviors. These studies demonstrate that gelsemine possesses significant anti-anxiety, glycine receptor-agonist and neuroinflammatory-inhibitory properties.
The in vivo anti-anxiety effect was investigated in male ICR mice subjected to CUMS, randomized into four groups (n = 10-12 per group): normal control, model, vehicle, and gelsemine (10 mg/kg). Drugs were administered intraperitoneally daily for 4 weeks. Anxiety‑related behaviors were evaluated via elevated plus‑maze and open‑field tests. Hypothalamic proteins were quantified by Western blotting; serum corticosterone and inflammatory cytokines were measured by ELISA. The results verified that gelsemine alleviates anxiety by activating glycine receptors, enhancing neurosteroid synthesis, and inhibiting NLRP3‑mediated neuroinflammation.

Custom Q&A

What is the molecular formula of Gelsemine free base?

The molecular formula of Gelsemine free base is C20H22N2O2.

What are some synonyms of Gelsemine free base?

Some synonyms of Gelsemine free base are GELSEMINE, Gelsemin, and NSC-21729.

What is the IUPAC name of Gelsemine free base?

The IUPAC name of Gelsemine free base is (1'R,2'S,3S,5'S,6'S,8'R,11'S)-2'-ethenyl-4'-methylspiro[1H-indole-3,7'-9-oxa-4-azatetracyclo[6.3.1.02,6.05,11]dodecane]-2-one.

What is the InChIKey of Gelsemine free base?

The InChIKey of Gelsemine free base is NFYYATWFXNPTRM-QJICHLCESA-N.

What is the CAS number of Gelsemine free base?

The CAS number of Gelsemine free base is 509-15-9.

What is the molecular weight of Gelsemine free base?

The molecular weight of Gelsemine free base is 322.4g/mol.

How many hydrogen bond donor counts are there in Gelsemine free base?

There is 1 hydrogen bond donor count in Gelsemine free base.

How many hydrogen bond acceptor counts are there in Gelsemine free base?

There are 3 hydrogen bond acceptor counts in Gelsemine free base.

How many rotatable bond counts are there in Gelsemine free base?

There is 1 rotatable bond count in Gelsemine free base.

What is the description of Gelsemine free base?

Gelsemine free base is a natural product found in Gelsemium sempervirens and Gelsemium elegans with available data.