Gelsemium

Gelsemium: A Comprehensive Reference

1. Identity, Botanical Classification, and Natural Source

Gelsemium belongs to the family Loganiaceae and comprises three species: the Asian Gelsemium elegans (Gardner & Champ.) Benth. and two related North American species, Gelsemium sempervirens (L.) J.St.-Hil. and Gelsemium rankinii Small. Gelsemium sempervirens, commonly known as yellow jasmine in North America, is not a close relative to the jasmines (Jasminum spp.) and is native to the southern regions of the United States spanning from Virginia to Florida. Its scientific name is Gelsemium sempervirens (L.) Ait., with common names including Carolina jasmine, Carolina jessamine, evening trumpet flower, woodbine, yellow jasmine, and yellow jessamine.

Gelsemium sempervirens L. is a perennial, twining shrub native to the southeastern United States and a member of the family Gelsemiaceae. It features slender, woody stems with opposite, lanceolate leaves, and produces bright yellow, fragrant, tubular flowers that predominantly bloom in spring.

Gelsemium elegans is known as Gou Wen, Da Cha Yao or Duan Chang Cao in China, and is distributed in the Fujian, Yunnan, Guizhou, Guangdong and Guangxi provinces in southern China and over southeastern Asia. Gelsemium rankinii is a rare species from the southeastern region of the United States with scarce pharmacological reports.

Common Forms and Preparations

The homeopathic preparation is a tincture made from the bark of the fresh root of Gelsemium sempervirens. Gelsemium sempervirens homeopathic dilutions are prepared from the mother tincture of plant roots according to the French Pharmacopoeia and supplied as a hydroalcoholic (30% ethanol) solution. The mother tincture was assayed to determine its gelsemine content, which proved to be 0.021%; since the molecular weight of this compound is 322.41, its concentration in the mother tincture was 6.5 × 10⁻⁴ moles/l.

The original extract (mother tincture, MT) is generally obtained by grinding the medicinal plant matter with a mortar and pestle and dissolving it in ethanolic solution. MT is diluted 100 times in 30% ethanol/distilled water to obtain the 1c dilution; subsequent serial 100× dilutions up to 29c, each followed by vigorous succussion (shaking), are then prepared in the same solvent using glass bottles.

Homeopathic Gelsemium preparations, particularly in common potencies like 30C or 200C, contain no measurable molecules of the original plant material due to extensive dilution. These preparations are generally considered safe when manufactured according to homeopathic pharmacy standards. However, lower potencies (such as mother tincture or 1X) may retain toxic properties and should only be used under professional guidance.

Current use of gelsemium is primarily homeopathic. The plant material is also used in traditional herbal medicine as a root tincture, though such use has substantially declined due to the plant's narrow therapeutic index.

2. Traditional and Historical Use

North American Traditions

Gelsemium sempervirens is listed in traditional homeopathic materials as a well-known remedy for the treatment of neuralgia, migraines, uterine pain, rheumatism, influenza, nausea, and whooping cough. Gelsemium sempervirens has been used since the nineteenth century in homeopathy for treating anxiety, neuralgia, migraine and spasmodic disorders, such as asthma and whooping cough in North America.

It was also widely used by traditional practitioners in the nineteenth century as a root tincture to cure fevers, diminish neuralgia, reduce inflammation and blood to the cerebrospinal centers, and to reduce spasmodic action. The reference King's American Dispensatory describes the medicinal usage of Gelsemium for the treatment of restlessness, mental irritability, and insomnia.

A historical Text-Book of Materia Medica, Pharmacology and Therapeutics states that Gelsemium has a distinct effect on sensory nerves and is useful for the treatment of pain. The drug appears to be most effective in treating trifacial neuralgia and neuralgia involving the inferior dental nerve. In addition, it was suggested to be efficacious for the treatment of discomfort related to dysmenorrhea, pruritus, and eczema.

In the United States, a homeopathic preparation of Gelsemium sempervirens is recommended for the treatment of headache and spasmodic disorders, such as asthma and whooping cough; it is further described as useful in treating dysmenorrhea, hysteria, chorea, and epilepsy. Although Gelsemium sempervirens was formerly extensively used to treat fevers, it is now mainly used to treat neuralgic pains, especially those involving the facial nerves.

Asian (Traditional Chinese Medicine) Traditions

Gelsemium elegans has been recognized as a toxic plant that is widely distributed in Southeast Asia and has been used as traditional Chinese medicine for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, and cancers for many years. Gelsemium elegans is a traditional herb used to treat certain types of skin ulcers, headaches, and cancer pain in China and other Asian countries.

As a traditional Chinese herbal medicine, G. elegans is used in folk remedies to treat various malignant dermal diseases and rheumatalgia. Extracts of these plants have traditionally been employed in Asian folk medicine to treat various illnesses, such as neuralgia, sciatica, and rheumatoid arthritis.

Preparation Methods in Traditional Use

Gelsemium primarily grows as a wild rattan plant in rural or remote mountainous regions. The entire plant is toxic, including the pollen, although the toxicity varies by part. The root, which contains the highest alkaloid content, is the most toxic, followed by the leaves.

3. Key Constituents and Active Compounds

Alkaloid Classes

Phytochemical studies of Gelsemium plants have identified more than 190 compounds, including alkaloids, iridoids, and steroids. Currently, at least 149 alkaloids with a basic structure of indole, oxindole, or bisindole nuclei have been isolated and identified in Gelsemium. According to the chemical skeleton, alkaloids are classified into six groups: gelsemine-type, gelsedine-type, sarpagine-type, humantenine-type, koumine-type, and yohimbane-type.

More than 120 alkaloids have been identified in G. sempervirens in addition to steroids, coumarins, and iridoids, and its use in traditional medicine has been traced back to these compound classes. Further research has reported the occurrence of various depsides and phenolic glycerides in G. sempervirens roots and rhizomes, consisting of benzoic and cinnamic acid derivatives as well as dicarboxylic acids.

Principal Bioactive Alkaloids

The three most pharmacologically investigated alkaloids are gelsemine, koumine, and gelsenicine:

• Gelsemine: Gelsemine is the principal active alkaloid from Gelsemium sempervirens Ait., and has produced antinociception in a variety of rodent models of painful hypersensitivity. Experimental studies indicate that gelsemine exhibits high acute toxicity, with an intraperitoneal LD50 in mice reported at approximately 49 mg/kg.
• Koumine: Koumine is a monoterpene alkaloid derived from the total alkaloids of Gelsemium, accounting for approximately 30% of the total alkaloid content. Koumine represents the principal component of Gelsemium alkaloids and exhibits comparable biological activity with relatively lower toxicity. Koumine is an indole alkaloid characterized by a unique hexacyclic cage structure, and its biological effects include anti-inflammation, antianxiety, analgesic, neuroprotection, and antitumor properties.
• Gelsenicine: Gelsenicine has the best analgesic effect among the G. elegans alkaloids. Gelsemium elegans is a plant of the Loganiaceae family known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity.

All parts of G. sempervirens contain the toxic strychnine-related alkaloids gelsemine, gelseminine, and sempervirine.

Among the principal alkaloids, koumine content is highest, followed by gelsemine, and gelsenicine has the highest toxicity. Gelsenicine has the highest toxicity, with LD50 values of ~0.26 mg/kg in rats intraperitoneally and 0.15 mg/kg intravenously in rats.

4. Mechanisms of Action

Glycine Receptor Modulation

To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABA_A receptors (GABA_ARs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined.

GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC50 of 31.5 ± 1.7 and 40.6 ± 8.2 μM, respectively). The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABA_ARs were inhibited by koumine and were insensitive to humantenmine.

Radioligand binding and displacement assays indicated that gelsemine and koumine, like glycine, were reversible and orthosteric agonists of glycine receptors with full efficacy and probably acted on the same binding site as the glycine receptor antagonist strychnine.

Spinal α3 Glycine Receptor / Allopregnanolone Pathway

Gelsemium and its active alkaloids may produce antinociception by activating the spinal α3 glycine/allopregnanolone pathway. Treatment with gelsemine, koumine, and glycine in primary cultures of spinal neurons concentration-dependently increased 3α-hydroxysteroid oxidoreductase (3α-HSOR) mRNA expression, which was inhibited by pretreatment with strychnine but not the glial inhibitor minocycline. Intrathecal injection of gelsemine, koumine, and glycine stimulated 3α-HSOR mRNA expression in the spinal cords of neuropathic rats and produced mechanical antiallodynia.

The antineuropathic pain effects of gelsemine were blocked by strychnine and after siRNA-mediated knock-down of spinal α3 glycine receptors, but not of α1 glycine receptors.

Anti-inflammatory Mechanisms

Microglia and astroglia are activated in the spinal dorsal horn post-incision, along with an increase of proinflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α). Both subcutaneous and intrathecal koumine treatment after incision significantly prevented mechanical allodynia and thermal hyperalgesia, inhibited microglial and astroglial activation, and suppressed expression of proinflammatory cytokines.

Effects on Neurotransmitter Systems

At higher concentrations, gelsemium tincture inhibits dopamine, noradrenaline, and serotonin uptake into synaptosomal preparations from different parts of the rat brain, whereas lower concentrations enhance noradrenaline and serotonin uptake into mesencephalon preparations.

Glycine Receptor Pathway and Analgesic Mechanism Summary

In contrast to morphine, when administered intrathecally and systemically, koumine, gelsemine, and gelsenicine have marked antinociception in inflammatory, neuropathic, and bone cancer pains without inducing antinociceptive tolerance. The results of preclinical studies support the potential clinical use of Gelsemium and suggest that its active alkaloids may be developed to treat intractable and other types of pain, preferably after chemical modification.

5. Scientific Evidence by Area of Use

5.1 Analgesia and Pain

Preclinical Evidence (Animal and In Vitro Studies):

A study examined the antinociceptive effects of gelsemine, the principal alkaloid in Gelsemium sempervirens. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50% to 60% and ED50 values of 0.5 to 0.6 μg. Multiple daily intrathecal injections of gelsemine for 7 days induced no tolerance to antinociception in the rat model of bone cancer pain.

Koumine, the main alkaloidal constituent of G. elegans Benth., significantly reduces both inflammatory and neuropathic pain in multiple preclinical models. Intraperitoneal administration of gelsemine exerted antinociceptive effects in partial sciatic nerve ligation mice at both the mechanical and thermal pain thresholds, and this effect lasted for approximately 4 hours after administration.

4 mg/kg gelsemine, which elicited antinociceptive effects, did not alter motor performance, suggesting that the analgesic effects of 4 mg/kg gelsemine were not the result of a motor side effect.

Gene ablation of the GlyR α3 subunit (α3 GlyR) but not α1 GlyR, by a 7-day intrathecal injection of siRNA targeting α3 GlyR or α1 GlyR, nearly completely prevented gelsemine-induced antinociception in neuropathic pain. This provides specific mechanistic evidence for the spinal α3 glycine receptor as the primary analgesic target.

Gelsenicine, the most toxic alkaloid derived from Gelsemium elegans Benth., has been reported to exert analgesic activity against inflammatory and neuropathic pain.

The PGE2-induced hyperalgesia model showed decreased expression levels of GlyRα3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE2-induced hyperalgesia by upregulating the expression of GlyRα3 and Gephyrin, which are key targets of the glycine receptor pathway.

Evidence Strength: All analgesic evidence is preclinical (animal models and in vitro). Studies have primarily evaluated the analgesic and anxiolytic effects of gelsemium in animals and in vitro. No clinical trial data support use of gelsemium for any indication.

5.2 Anxiety and Psychobehavioral Effects

Animal Studies:

One study was designed to investigate the putative anxiolytic-like activity of ultra-low doses of G. sempervirens, produced according to the homeopathic pharmacopeia. Five different centesimal (C) dilutions of G. sempervirens (4C, 5C, 7C, 9C, and 30C), the drug buspirone (5 mg/kg), and solvent vehicle were delivered intraperitoneally to groups of ICR-CD1 mice over a period of 9 days. The behavioral effects were assessed in the open-field and light-dark tests in blind and randomized fashion. Most G. sempervirens dilutions did not affect the total distance traveled in the OF (only the 5C had an almost significant stimulatory effect on this parameter), indicating that the medicine caused no sedation effects or unspecific changes in locomotor activity.

Homeopathic doses of G. sempervirens positively influenced the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a decrease in thigmotaxis or neophobia.

Experimental studies revealed that Gelsemium sempervirens alters mice's emotional responses to new environments, promoting exploratory behavior while reducing thigmotaxis.

Mechanistic (Cellular) Studies:

The anxiolytic property related to Gelsemium extracts has been quite exclusively associated with the alkaloid gelsemine; yet, Gelsemium plants contain many further alkaloids with anxiolytic potential, suggesting that the anti-anxiety activity of Gelsemium sempervirens may come indifferently from gelsemine, koumine, or gelsevirine, or a complex mixture of several active alkaloids.

Human/Clinical Evidence:

Earlier studies by Guillemin 1989 and Cardenne 1991 demonstrated comparable efficacy of Gelsemium sempervirens and a benzodiazepine for treating anxiety in two groups of 60 subjects. These studies have been reported by Scheepers and van Wassenhoven. However, these studies are methodologically limited and reported only in secondary sources.

A phase III randomized controlled trial of 180 subjects tested the efficacy of Gelsemium sempervirens for anxiety when not individualized. The specifics of this trial's outcomes are not fully detailed in available sources.

The available preclinical studies provide basic knowledge of the pharmacological effects of G. sempervirens but clinical research on the anxiolytic effect of this drug in humans is based only on empirical knowledge and not on fundamental evidence supplied by controlled investigations.

Evidence Strength: Predominantly animal/preclinical. Human evidence is very limited and methodologically weak. No well-powered, adequately controlled clinical trials are available.

5.3 Anticancer Activity

Preclinical Evidence:

In the context of cancer, koumine has shown marked cytotoxic effects against leukemia, liver cancer, breast cancer, lung cancer, and colon cancer cells.

Koumine induced the apoptosis of SW480 human colon cancer cells and blocked the S/G2 transition in the cell cycle.

Koumine-like compounds were evaluated for antiproliferative activity against four human cancer cell lines, including HT-29, HCT-116, HCT-15, and Caco-2. Most compounds exhibited much higher antiproliferation activities (IC50 <10 μM) than koumine. Two selected compounds showed comparable antitumor effects to 5-FU in vivo, as well as better safety profiles.

Although the plants of the genus Gelsemium hold great potential to be developed as antitumor drugs, their toxicity could not be ruled out.

Evidence Strength: All anticancer evidence is preclinical (cell culture and animal models). No human clinical trials have been conducted for oncological applications of Gelsemium alkaloids.

5.4 Anti-inflammatory and Immunomodulatory Effects

The crude extracts, as well as the monomeric compounds, from the genus possess anti-tumor, analgesic, anxiolytic, anti-inflammatory, and immunomodulating pharmacological activities.

Preclinical studies have demonstrated the therapeutic effects of koumine in neuropathic pain, arthritis, and autoimmune liver injury. In the context of cancer, koumine has shown marked cytotoxic effects against leukemia, liver cancer, breast cancer, lung cancer, and colon cancer cells.

The antitumor, anti-stress, and anti-psoriasis activities of koumine have been reported in preclinical research.

Evidence Strength: Preclinical only. No adequate human clinical trials in inflammation or immune modulation have been published.

5.5 Neuropathic Pain and Sleep Disturbance

Gelsemine, an alkaloid from Gelsemium elegans, is effective in mitigating chronic pain in rats. In a study, the alkaloid was investigated for whether it improved sleep disturbance, the most common comorbid symptom of chronic pain, in a mouse model of neuropathic pain. Mice were subjected to partial sciatic nerve ligation. After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia, thermal hyperalgesia, and electroencephalogram/electromyogram recordings were assessed.

Evidence Strength: Animal model evidence only. No human trials have been conducted.

5.6 Gene Expression Effects in Neuronal Cells

Research investigated the gene expression of a human neurocyte cell line treated with various dilutions of Gelsemium's extract (2c, 3c, 4c, 5c, 9c, and 30c). Human SH-SY5Y neuroblastoma cells, which are often used as in vitro models of neuronal function and differentiation, were used. This represents in vitro cellular evidence only, with unclear clinical relevance.

6. Body Systems and Health Areas

Gelsemium extract and its active alkaloids serve a variety of biological functions, including neurobiological, immunosuppressive, and antitumor effects, and have traditionally been used to treat pain, neuralgia, anxiety, insomnia, asthma, respiratory ailments, and cancers.

• Central Nervous System: Gelsemium species are categorized under medicinal as well as poisonous plants. Among various species, G. elegans and G. sempervirens possess medicinal value and have been traditionally used as nervous system relaxants.
• Pain Pathways (Spinal): The antinociceptive effects of Gelsemium alkaloids have been studied since the 1970s, with more investigations emerging recently. When given systemically or intrathecally, Gelsemium's total alkaloid extracts and major active alkaloids have been shown to be antinociceptive in a variety of pain models.
• Immune System: In recent years, studies have shown that Gelsemium monoterpenoid indole alkaloids exhibit extensive beneficial pharmacological activities, which primarily focus on analgesic, anti-tumour, anxiolytic, immunosuppressive, and anti-inflammatory aspects.
• Respiratory System: Different alkaloids have inhibitory effects on the respiratory centre in the medulla oblongata and anterior horn cells of the spinal cord, which can result in respiratory depression and muscle paralysis in toxic doses.
• Dermatological: Gelsemium possesses pharmacological activities including dermatological effects alongside anti-inflammatory, analgesic, sedative, anxiolytic, and anticancer effects.

7. Dosage Forms and Dosages Reported in Studies

No standardized clinical dosage has been established for Gelsemium in conventional medicine. The following dosages have been specifically reported in published research:

• Homeopathic potencies (animal research): Five different centesimal (C) dilutions of G. sempervirens — 4C, 5C, 7C, 9C, and 30C — were delivered intraperitoneally to groups of ICR-CD1 mice over a period of 9 days, alongside buspirone (5 mg/kg) as comparator.
• Gelsemine (intrathecal, rat model): A single intrathecal injection of gelsemine produced antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy, with ED50 values of 0.5 to 0.6 μg.
• Gelsemine (intraperitoneal, mice): 4 mg/kg gelsemine elicited antinociceptive effects without altering motor performance in partial sciatic nerve ligation mice.
• Gelsebanine (mice): 2–4 mg/kg gelsebanine alleviated anxiety and nerve pain in mice without showing significant toxicity to the animals, indicating that <2 mg/kg gelsebanine may be safe for animals.
• Total alkaloids of G. elegans (mice): The LD50 of total alkaloids of G. elegans was 15 mg/kg by oral administration and 4 mg/kg by intraperitoneal injection in mice.
• Koumine and gelsemine LD50 (mice): Koumine (LD50 = 99.0 mg/kg) and gelsemine (LD50 = 56.2 mg/kg) are the compounds with the highest content in Gelsemium.
• Historical clinical dosage (19th century): For insomnia from exhaustion or excitement, historical prescriptions cited the dose as half to two minims, or not exceeding five minims, and may be repeated at intervals of an hour, where it was believed to act as a gentle stimulant to the exhausted nerve centres.

Due to the fact that the therapeutic dose of Gelsemium is close to the toxic dose, it is necessary to identify the appropriate dose or the exact chemical components of Gelsemium with high efficiency and low toxicity and to clarify the pharmacological and toxicological effects.

8. Safety Considerations and Toxicology

Narrow Therapeutic Index

Toxicological studies have confirmed high toxicity of Gelsemium species at higher doses. These plants have a narrow therapeutic index; that is, the margin between therapeutic efficacy and toxic value is very small. Toxicological studies have confirmed high toxicity at higher doses, and these plants have a narrow therapeutic index.

The therapeutic dose is very close to the toxic dose, making accidental ingestion potentially fatal.

Toxic Alkaloid Profile

More than 120 alkaloids have been identified in Gelsemium, categorized into six groups based on their chemical structures: sarpagine-type, gelsemine-type, gelsedine-type, humantenine-type, koumine-type, and yohimbane-type. According to research findings on the acute toxicity of Gelsemium alkaloid extracts and monomers in rats and mice, there is significant variation in toxicity among different types of Gelsemium alkaloids. The 50% lethal dose (LD50) in mice after intravenous administration of gelsemine-type alkaloids is 78.23 mg/kg. The LD50 value of koumine-type after intraperitoneal injection is more than 50 mg/kg.

Gelsenicine has the highest toxicity, with LD50 values of approximately 0.26 mg/kg in rats intraperitoneally and 0.15 mg/kg intravenously in rats — classifying it as an extremely toxic compound.

Symptoms of Poisoning

Ingestion of as little as 4 mL of a fluid extract has been reported to be fatal. Toxic symptoms include sweating, dizziness, nausea, vomiting, muscle weakness, dilated pupils, paralysis, blurry vision, difficulty breathing, seizures, and coma. The nervous system is overly depressed in cases of severe poisoning, leading to death.

GEB (G. elegans Benth.) poisoning mainly involves damage to the nervous system, the digestive system, and the respiratory system, with common symptoms of vomiting, dizziness, abdominal pain, respiratory depression, convulsion, coma, and spasms.

Common symptoms of poisoning include severe sedation, dizziness and headache, blurred vision, muscle weakness, and respiratory depression. In severe cases, respiratory failure may occur, which is the primary cause of death in acute poisoning. The neurotoxicity of gelsemine is primarily associated with its ability to interfere with inhibitory neurotransmission in the central nervous system.

Mechanism of Toxicity

Different alkaloids have inhibitory effects on the respiratory centre in the medulla oblongata and anterior horn cells of the spinal cord, resulting in respiratory depression and muscle paralysis. Pharmacological studies have shown that these alkaloids also act on type A GABA receptors in the central nervous system, causing CNS depression and respiratory and circulatory failure in poisoned individuals.

Plant Part Toxicity Gradient

It is generally recognized that the whole plant of G. elegans Benth. is highly toxic, with stronger toxicity in the root and young leaf tissues, and the strongest toxicity in the root bark, which causes poisoning through oral administration.

Animal and Environmental Toxicity

Toxicity has been reported in animals that have grazed on Gelsemium, and bees that pollinate the plant have been poisoned. Honey derived from the plant nectar has been reported to be toxic. In animal studies, toxicity has manifested as reductions in motor activity and respiratory rate and the presence of tremors and clonic seizures, with death resulting from asphyxia.

Misidentification Risk

Gelsemium may be mistaken for various lookalike benign herbs, leading to inadvertent consumption and poisoning. This misidentification risk is a well-documented public health concern particularly in Southeast Asian communities using herbal remedies.

Regulatory Status

In October 2025, the FDA issued a warning letter to a pharmacy regarding homeopathic products containing Gelsemium marketed for flu symptoms. The agency's concerns centered on making specific disease treatment claims without adequate evidence and proper FDA approval.

No Established Drug Interaction Data

No clinical trial data support use of gelsemium for any indication; use is not advised due to known toxicity of the plant parts. Given the mechanism of action on glycine receptors and GABA_A receptors documented in preclinical studies, theoretical interactions with CNS depressants, GABAergic drugs, and anticonvulsants are mechanistically plausible, but no formal clinical drug-interaction studies have been published.

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