Gelsemine

Last updated
Gelsemine
Gelsemine.svg
Gelsemine (gelsemin), an indole alkaloid
Clinical data
ATC code
  • none
Identifiers
  • 3-ethenyl-1-methyl-2,3,3a,7,8,8a-hexahydro-1h,5h-spiro[3,8,5-(ethane[1,1,2]triyl)oxepino[4,5-b]pyrrole-4,3'-indol]-2'(1'h)-one
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C20H22N2O2
Molar mass 322.408 g·mol−1
3D model (JSmol)
  • CN1C(C2CO3)[C@@H]4[C@]5(C(C=CC=C6)=C6NC5=O)[C@H]3C[C@H]2[C@]4(C=C)C1
  • InChI=1S/C20H22N2O2/c1-3-19-10-22(2)16-11-9-24-15(8-13(11)19)20(17(16)19)12-6-4-5-7-14(12)21-18(20)23/h3-7,11,13,15-17H,1,8-10H2,2H3,(H,21,23)/t11-,13+,15+,16+,17-,19-,20-/m0/s1
  • Key:NFYYATWFXNPTRM-QJICHLCESA-N

Gelsemine (C20H22N2O2) is an indole alkaloid isolated from flowering plants of the genus Gelsemium , a plant native to the subtropical and tropical Americas, and southeast Asia, and is a highly toxic compound that acts as a paralytic, exposure to which can result in death. It has generally potent activity as an agonist of the mammalian glycine receptor, the activation of which leads to an inhibitory postsynaptic potential in neurons following chloride ion influx, and systemically, to muscle relaxation of varying intensity and deleterious effect. Despite its danger and toxicity, recent pharmacological research has suggested that the biological activities of this compound may offer opportunities for developing treatments related to xenobiotic or diet-induced oxidative stress, and of anxiety and other conditions, with ongoing research including attempts to identify safer derivatives and analogs to make use of gelsemine's beneficial effects. [1] [2]

Contents

Natural sources

Example of a Gelsemium species, from which gelsemine is isolated Gelsemium sempervirens, its principal source in the Americas. Gelsemium sempervirens 001.JPG
Example of a Gelsemium species, from which gelsemine is isolated Gelsemium sempervirens, its principal source in the Americas.

Gelsemine is found in, and can be isolated from, the subtropical to tropical flowering plant genus Gelsemium , family Loganiaceae, which as of 2014 included five species, where G. sempervirens Ait., the type species, is prevalent in the Americas and G. elegans Benth. in China and East Asia. [3] [4] The species in the Americas, G. sempervirens, has a number of common names that include yellow or Carolina jasmine (or jessamine), gelsemium, evening trumpetflower, and woodbine. [5] [6] The plant genus is native to the subtropical and tropical Americas, e.g., in Mexico, Honduras, Guatemala, and Belize, [4] as well as to China and southeast Asia. [4] The species is prized for its "heavily fragrant yellow flowers," and has been cultivated since mid-seventeenth century (in Europe). [4] It is found in southeastern and south-central states of the U.S., [5] and as a garden plant in warmer areas where it can be trained to grow over arbors or to cover walls (see image). [7]

All plant parts of the herbage and exudates of this genus, including its sap and nectar, appear to contain gelsemine and related compounds, [8] as well as a wide variety of further alkaloids and other natural products. [3] The plant's herbage, in particular, is known to contain several toxic alkaloids, and is generally known to be poisonous to livestock and humans. [4]

Chemistry

Numbering of gelsemine GELSEMINA.png
Numbering of gelsemine

Gelsemine was isolated from G. sempervirens Ait., in 1870. [9] [10] Its chemical formula was determined to be C20H22N2O2, thus with a molecular weight of 322.44 g/mol. [11] Its structure was finally determined, by X-ray crystallographic analysis and by nuclear magnetic resonance (NMR) spectroscopy, in 1959 by Conroy and Chakrabarti. [12] [9] [10]

It is a monoterpenoid type of indole alkaloid, [13] and a close relative of the natural product gelseminine, which is also present from the same natural sources. [8] The gelsemine class of alkaloids are some of a wide variety of the alkaloid and other natural products that have been isolated from this genus of plants. [3]

Secologanin.png
secologanin
Tryptamine.svg
tryptamine
Strictosidine.svg
3α(S)-strictosidine (isovincoside)
Strictosidine and its precursors, line-angle representations. 3α(S)-strictosidine (isovincoside) is a key intermediate on the biosynthetic pathway of gelsemine, and it is the common precursor for essentially all monoterpenoid indole alkaloids. Strictosidine is derived in one enzyme-catalyzed step from tryptamine and secologanin (the latter of which, a terpene, is ultimately derived from mevalonic acid).

Gelsemine's biosynthesis, as of 1998, is thought to proceed from 3α(S)-strictosidine (isovincoside), the common precursor for essentially all monoterpenoid indole alkaloids—itself deriving directly from mevalonic acid-derived secologanin and tryptamine. [14] [13] : p. 629  From strictosidine, the biosynthesis proceeds through five intermediates—including koumicine (akkuammidine), koumidine, vobasindiol, anhydrovobasindiol, and gelsenidine (humantienine-type). [13] : p. 629  [15] The related alkaloids koumine and gelsemicine also derive from this pathway (koumine from anhydrovobasindiol via oxidation and rearrangement, and gelsemicine from gelsemine itself, via aromatic oxidation and O-methylation). [13] : p. 629  [15] : p. 132ff  For the chemical synthesis (natural product synthesis, studies and total synthesis), see the separate section below.

Summary of biological activities

Full sections in following are devoted to specific activities of gelsemine. Noted are the facts that it is a highly toxic compound, where exposure can result in paralysis and death. It is reported to be a glycine receptor agonist with significantly higher binding affinity for some of these receptors than its native agonist, glycine. In addition, it has been shown to have effects on pathways/systems in model animals (rat, rabbit), related to xenobiotic- or diet-induced oxidative stress, and in the treatment of anxiety and other conditions.

History

Gelsimium extracts, and so gelsemine, indirectly, have been the subject of serious scientific study for over a hundred years. On the medical side, gelsemium tinctures were used in the treatment of neuralgia by physicians in England, in the late 19th century; Arthur Conan Doyle, the noted author who first trained as a physician, after observing the success of such treatments, ingested increasing doses of a tincture daily, to “ascertain how far one might go in taking the drug, and what the primary symptoms of an overdose might be,” submitting his first career publication on this in the British Medical Journal. [16] [primary source] On the chemistry side, the December 1910 meeting of the Division of Pharmaceutical Chemistry, of the American Chemical Society, reports among the papers read, the "Assay of Gelsemium" by L.E. Sayre. [17] [primary source]

Mechanisms of action

Gelsemine is an agonist for the glycine receptor (GlyR) with a much greater affinity for studied examples of this receptor than glycine. [18] These receptors are ligand-gated ion channels which affect a variety of physiological processes. When glycine receptors are activated by agonist binding to at least two of the five agonist binding sites, chloride ions enter the neuron. This causes an inhibitory postsynaptic potential, which, systemically, leads to muscle relaxation. [19] [20]

Toxicity and toxicology

In mice, it has been shown to have an LD50 of 56 mg/kg (intraperitoneal), [21] and a lowest lethal dose (LDLo) of 0.1-0.12 mg/kg (intravenous). [22] In rabbits, the LDLo was 0.05-0.06 mg/kg (intravenous). [22] In frogs, the LDLo was 20–30 mg/kg (subcutaneous). [22] In dogs, the LDLo was 0.5-1.0 mg/kg (intravenous). [22] In parson, the LD50 was 0.05 mg/kg

The sap of the plant may cause skin irritation in sensitive individuals, and there are reports that inhalation from the flowers alone may, in some cases, lead to human poisoning (see below, where insect death at such flowers is likewise reported). [4]

The plant's herbage is known to contain several toxic alkaloids, and while there is report of its feeding to pigs, it is generally considered to be an abortifacient and lethal poison when livestock or other animals feed on its leaves. [4] It has been reportedly used as a fish poison as well, e.g., on the island of Borneo. [4]

Human poisonings are known, including pediatric and adult cases, and in the case of adults, both accidental and intentional poisonings. At lower doses in humans, the inhibitory postsynaptic potential induced by gelsemine action at the glycine receptor can result in nausea, diarrhea and muscle spasms caused by loss of involuntary muscle control; at higher doses, vision impairment or blindness, paralysis, and death can occur.[ citation needed ] Children, mistaking the flower of G. sempervirens for honeysuckle, have been poisoned by sucking the nectar from the flower; its ingestion has been associated with honey bee (but not bumble bee) fatalities as well (e.g., in the southeast U.S.). [23] [ page needed ] [4] [24] It has been reportedly used, via ingestion or smoking, as a poison in cases of suicide, in China, Vietnam, and Borneo. [4]

Treatment

Gelsemine is a highly toxic and therefore possibly fatal substance for which there is no antidote, but the symptoms can be managed in low dose intoxications. In the case of an oral exposure a gastric lavage is performed, which must be done within approximately one hour of ingestion. Activated charcoal is then administered to bind the free toxin in the gastrointestinal tract to prevent absorption. Benzodiazepine or phenobarbital is also generally administered to help control seizing, and atropine can be used to treat bradycardia. Electrolyte and nutrient levels are monitored and controlled. [11]

In the case of a skin exposure, the area is washed with soap and water for 15 minutes to avoid skin damage. [11]

While there is no current treatment to reverse the effects of gelsemine poisoning, preliminary research done in rats has suggested that strychnine has potential therapeutic applications due to its antagonistic effects at the glycine receptor, resulting in a counteraction of some downstream effects such as the increase in allopregnanolone production associated with gelsemine poisoning. [25] [19]

Chemical synthesis

The chemical synthesis of gelsemine has been an active target of interest since the early 1990s, given its place among the alkaloids, and its complex structure (seven contiguous stereocenters and six rings). [9] [12] Although the full mechanism of its biosynthesis is still being investigated, many research groups have successfully synthesized it using chemical means. [12] [26] [27] The first racemic total synthesis of gelsemine was in 1994, by W.N. Speckamp's group, with a remarkable first yield of 0.83% (given the subsequent range, prior to 2014, of 0.02-1.2%). [28] [9] [29]

Eight further total syntheses have been reported in the literature, including from the groups of A.P. Johnson in 1994, T. Fukuyama in 1996 and again in 2000, D.J. Hart in 1997, L.E. Overman in 1999, S.J. Danishefsky in 2002, and Y. Qin in 2012, with the latter Fukuyama group synthesis (31 steps, 0.86%) and the Qin group synthesis (25 steps, 1%) being asymmetric. [30] [31] [32] [33] [34] [35] [36] [9] A further asymmetric synthesis using an organocatalytic Diels–Alder approach from the F.G. Qiu and H. Zhai groups in China, reporting a remarkable 12 steps and a 5% yield, was reported in 2015. [9] Additional synthetic approaches were discussed by notable scientists such as Fleming, Stork, Penkett, Pearson, Aubé, Vanderwal, and Simpkins. [37]

Reaction scheme for W.N. Speckamp's first racemic total synthesis of gelsemine. Gelsemine first synthesis.jpg
Reaction scheme for W.N. Speckamp's first racemic total synthesis of gelsemine.

Potential medical applications

Modern medical utility

Pharmacological research has suggested gelsemine activities to have potential related to the treatment of anxiety, and in treatments of conditions involving oxidative stress. In addition, gelsemine has been noted to have anti-inflammatory and anti-cancer activities. Recent research on gelsemine has included investigations aimed at developing safer gelsemine analogs and derivatives that might allow safe application of the compounds beneficial effects.[ citation needed ]

The identified anxiolytic effects of preparations derived from Gelsemium sempervirens are believed due to in largest part to the presence of gelsemine in such preparations. [38] [ verification needed ] Based on a rat study, use of gelsemine has been reported as being potentially effective, where the comparison was to treatment with Diazepam. [39] [primary source]

Gelsemine has been suggested to have potential in offering protective effects against oxidative stress. In a small rat study, the off-target effects of cisplatin—nephrotoxicity arising from its induction of pathways that generate reactive oxygen species, a factor impacting its use in cancer treatment—were examined, and gelsemine was found to significantly attenuate cisplatin-induced damage to DNA, and further general damage due to oxidative mechanisms. Inhibition of xanthine oxidase and lipid peroxidation activities were noted, along with "increased production and/or activity of anti-oxidants, both enzymatic... and non-enzymatic...". [40] [primary source][ better source needed ]

In a small rabbit study, the impact of gelsemine administration on parameters relating to diet-induced hyperlipidemia was examined, where gelsemine was observed to improve lipid profile parameters associated with hyperlipidemia to a significant extent, as well as to "decreas[e] hyperlipidemia-induced oxidative stress in a dose-dependent manner," as determined by altered activities of a number of relevant metabolite and enzyme activity levels. The results, taken together, led the study authors to conclude that supplements of gelsemine to animals exposed to high fat diets may be of use in reversing the effects and in protecting tissues from oxidative stress resulting from such diets. [41] [primary source][ better source needed ]

Gelsemine has been observed to have anti-inflammatory activity.[ clarification needed ] [40] [primary source][ better source needed ]

Gelsemine has been observed to have anti-cancer activity.[ clarification needed ] [40] [primary source][ better source needed ]

Traditional medical uses

Preparations from the plant from which gelsemine derives, Gelsemium sempervirens, have been used as treatment for a variety of ailments, for instance, through use of Gelsemium tinctures.[ citation needed ] Applications have included treatment of acne, anxiety, ear pain, migraine, and more generally with diseases associated with an inflammatory response, and in cases of abnormal nervous function (paralysis, “pins and needles” feeling, neuralgia, etc.). [42] [ better source needed ][primary source][ unreliable source ]

Gelsemine is used indirectly, via the use of "yellow jasmine", in the 1927 Agatha Christie novel, The Big Four , where an injection of this natural preparation is used to kill the character Mr. Paynter. [43] [ page needed ] It is then used directly, in 2013, as gelsemine, in series 13 of the ITV series, Agatha Christie's Poirot , as the agent to immobilize the character Stephen Paynter (played by Steven Pacey) before his being burnt to death, thus implicating the character Madame Olivier, a research neuroscientist (played by Patricia Hodge); and also, directly, to paralyze and immobilize Olivier and another character after their kidnappings. [44]

In House of Cards season 5 episode 12, Jane Davis offers Claire Underwood gelsemine as a headache reliever, noting that she should only use two drops. Later on, Claire uses the gelsemine to murder Tom Yates, her lover, by putting it into his drink without his knowledge. [45]

In episode 9 of season 3 of iZombie , the victim is poisoned by gelsemine. [46]

See also

Related Research Articles

<span class="mw-page-title-main">Aconitine</span> Toxic plant alkaloid

Aconitine is an alkaloid toxin produced by various plant species belonging to the genus Aconitum, known also commonly by the names wolfsbane and monkshood. Monkshood is notorious for its toxic properties.

<span class="mw-page-title-main">Salvinorin A</span> Chemical compound

Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.

<span class="mw-page-title-main">Strychnine</span> Poisonous substance used as pesticide

Strychnine is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the eyes or mouth, causes poisoning which results in muscular convulsions and eventually death through asphyxia. While it is no longer used medicinally, it was used historically in small doses to strengthen muscle contractions, such as a heart and bowel stimulant and performance-enhancing drug. The most common source is from the seeds of the Strychnos nux-vomica tree.

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Yohimbine</span> Chemical compound

Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree Pausinystalia johimbe; also from the bark of the unrelated South American tree Aspidosperma quebracho-blanco. Yohimbine is an α2-adrenergic receptor antagonist, and has been used in a variety of research projects. It is a veterinary drug used to reverse sedation in dogs and deer.

<span class="mw-page-title-main">Picrotoxin</span> Chemical compound

Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison). A mixture of two different compounds, picrotoxin occurs naturally in the fruit of the Anamirta cocculus plant, although it can also be synthesized chemically.

<i>Gelsemium</i> Genus of plants

Gelsemium is an Asian and North American genus of flowering plants belonging to family Gelsemiaceae. The genus contains three species of shrubs to straggling or twining climbers. Two species are native to North America, and one to China and Southeast Asia.

<span class="mw-page-title-main">Epibatidine</span> Toxic chemical from some poison dart frogs

Epibatidine is a chlorinated alkaloid that is secreted by the Ecuadoran frog Epipedobates anthonyi and poison dart frogs from the Ameerega genus. It was discovered by John W. Daly in 1974, but its structure was not fully elucidated until 1992. Whether epibatidine is the first observed example of a chlorinated alkaloid remains controversial, due to challenges in conclusively identifying the compound from the limited samples collected by Daly. By the time that high-resolution spectrometry was used in 1991, there remained less than one milligram of extract from Daly's samples, raising concerns about possible contamination. Samples from other batches of the same species of frog failed to yield epibatidine.

Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy.

<span class="mw-page-title-main">Arecoline</span> Mild stimulant

Arecoline is a nicotinic acid-based mild parasympathomimetic stimulant alkaloid found in the areca nut, the fruit of the areca palm. It is an odourless oily liquid. It can bring a sense of enhanced alertness and energy along with mild feelings of euphoria and relaxation. The psychoactive effects are comparable to that of nicotine.

<span class="mw-page-title-main">Aporphine</span> Chemical compound

Aporphine is an alkaloid with the chemical formula C17H17N. It is the core chemical substructure of the aporphine alkaloids, a subclass of quinoline alkaloids. It can exist in either of two enantiomeric forms, (R)-aporphine and (S)-aporphine.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Allopregnanolone</span> Endogenous inhibitory neurosteroid

Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum depression. It is given by injection into a vein.

<span class="mw-page-title-main">Epiboxidine</span> Chemical compound

Epiboxidine is a chemical compound which acts as a partial agonist at neural nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. It was developed as a less toxic analogue of the potent frog-derived alkaloid epibatidine, which is around 200 times stronger than morphine as an analgesic but produces extremely dangerous toxic nicotinic side effects.

<span class="mw-page-title-main">Higenamine</span> Chemical compound

Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including Nandina domestica (fruit), Aconitum carmichaelii (root), Asarum heterotropioides, Galium divaricatum, Annona squamosa, and Nelumbo nucifera.

<span class="mw-page-title-main">Histrionicotoxins</span>

Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the family Dendrobatidae, notably Oophaga histrionica, which are native to Colombia. It is likely that, as with other poison frog alkaloids, histrionicotoxins are not manufactured by the amphibians, but absorbed from insects in their diet and stored in glands in their skin. They are notably less toxic than other alkaloids found in poison frogs, yet their distinct structure acts as a neurotoxin by non-competitive inhibition of nicotinic acetylcholine receptors.

A convulsant is a drug which induces convulsions and/or epileptic seizures, the opposite of an anticonvulsant. These drugs generally act as stimulants at low doses, but are not used for this purpose due to the risk of convulsions and consequent excitotoxicity. Most convulsants are antagonists at either the GABAA or glycine receptors, or ionotropic glutamate receptor agonists. Many other drugs may cause convulsions as a side effect at high doses but only drugs whose primary action is to cause convulsions are known as convulsants. Nerve agents such as sarin, which were developed as chemical weapons, produce convulsions as a major part of their toxidrome, but also produce a number of other effects in the body and are usually classified separately. Dieldrin which was developed as an insecticide blocks chloride influx into the neurons causing hyperexcitability of the CNS and convulsions. The Irwin observation test and other studies that record clinical signs are used to test the potential for a drug to induce convulsions. Camphor, and other terpenes given to children with colds can act as convulsants in children who have had febrile seizures.

<span class="mw-page-title-main">Tutin (toxin)</span> Chemical compound

Tutin is a poisonous plant derivative found in New Zealand tutu plants. It acts as a potent antagonist of the glycine receptor, and has powerful convulsant effects. It is used in scientific research into the glycine receptor. It is sometimes associated with outbreaks of toxic honey poisoning when bees feed on honeydew exudate from the sap-sucking passion vine hopper insect, when the vine hoppers have been feeding on the sap of tutu bushes. Toxic honey is a rare event and is more likely to occur when comb honey is eaten directly from a hive that has been harvesting honeydew from passionvine hoppers feeding on tutu plants.

<span class="mw-page-title-main">Mitragynine</span> Opioid analgesic compound

Mitragynine is an indole-based alkaloid and the most abundant active alkaloid in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. The total alkaloid concentration in dried leaves ranges from 0.5 to 1.5%. In Thai varieties, mitragynine is the most abundant component while 7-hydroxymitragynine is a minor constituent. In Malaysian kratom varieties, mitragynine is present at lower concentration. Such preparations are orally consumed and typically involve dried kratom leaves which are brewed into tea or ground and placed into capsules. Mitragynine consumption for medicinal and recreation purposes dates back centuries, although early use was primarily limited to Southeast Asian countries such as Indonesia and Thailand where the plant grows indigenously. Recently, mitragynine use has spread throughout Europe and the Americas as both a recreational and medicinal drug. While research into the effects of kratom have begun to emerge, investigations on the active compound mitragynine are less common.

<span class="mw-page-title-main">14-Hydroxygelsenicine</span> Indole alkaloid found in some plants

14-Hydroxygelsenicine (HGE) is a gelsedine-type indole alkaloid naturally found in some plants of the Gelsemium genus. G. elegans was used in traditional Chinese medicine as a remedy for a plethora of conditions such as skin ulcers and dermatitis, pain related to cancer, rheumatic arthritis, psoriasis as well as to treat bone fractures. It can also be found under the names “Duan Chang Cao”, “Gou Wen” and “heartbreak grass”. G. elegans is also known for its toxic effects; it is used by hilltribes of southeastern Asia as an effective means of committing suicide and has been linked to certain types of toxic honey, where HGE was the most abundant component. Gelsedine-type alkaloids from G. elegans usually express high toxicity, with gelsenicine being one of the most toxic. However, toxicity of HGE has not yet been thoroughly researched. More recent studies have shown that alkaloids derived from G. elegans have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the toxic dose being close to the therapeutic dose.

References

  1. ↑ Lin, Lin; Zheng, Jing; Zhu, Weiping; Jia, Ning (2015-03). "Nephroprotective Effect of Gelsemine Against Cisplatin-Induced Toxicity is Mediated Via Attenuation of Oxidative Stress". Cell Biochemistry and Biophysics. 71 (2): 535–541. doi:10.1007/s12013-014-0231-y. ISSN 1085-9195.
  2. ↑ Liu, Ming; Huang, Hui-Hui; Yang, Jian; Su, Yan-Ping; Lin, Hong-Wei; Lin, Li-Qing; Liao, Wei-Jian; Yu, Chang-Xi (2013-02). "The active alkaloids of Gelsemium elegans Benth. are potent anxiolytics". Psychopharmacology. 225 (4): 839–851. doi:10.1007/s00213-012-2867-x. ISSN 0033-3158
  3. 1 2 3 4 Zhang JY, Wang YX (January 2015). "Gelsemium analgesia and the spinal glycine receptor/allopregnanolone pathway". Fitoterapia. 100 (C, November): 35–43. doi:10.1016/j.fitote.2014.11.002. PMID   25447163.
  4. 1 2 3 4 5 6 7 8 9 10 11 Ornduff R (1970). "The Systematics and Breeding System of Gelsemium (Loganiceae)" (review). Journal of the Arnold Arboretum. 51 (1): 1–17. doi: 10.5962/bhl.part.7036 . Retrieved February 18, 2017.
  5. 1 2 "Gelsemium sempervirens". Germplasm Resources Information Network . Agricultural Research Service, United States Department of Agriculture . Retrieved February 12, 2008.
  6. ↑ USF-PA Staff (February 18, 2017). "Gelsemium sempervirens" (database entry). Atlas of Florida Vascular Plants. University of South Florida. Retrieved February 18, 2017.
  7. ↑ "Gelsemium sempervirens Carolina jessamine from New Moon Nurseries". www.newmoonnursery.com. New Moon Nursery.
  8. 1 2 Drugs.com Staff (2009). "Gelsemium sempervirens" (database entry). Drugs.com. Alphen aan den Rijn, NLD: Wolters Kluwer Health.
  9. 1 2 3 4 5 6 Chen X, Duan S, Tao C, Zhai H, Qiu FG (May 2015). "Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach". Nature Communications. 6 (7204): 7204. Bibcode:2015NatCo...6.7204C. doi:10.1038/ncomms8204. PMC   4647982 . PMID   25995149. Note, the use of Chen et al. is, in part, for the thorough manner in which it reviews the earlier literature on synthetic efforts toward, and total syntheses of the gelsemine target.
  10. 1 2 Lin H, Danishefsky SJ (January 2003). "Gelsemine: a thought-provoking target for total synthesis". Angewandte Chemie. 42 (1): 36–51. doi:10.1002/anie.200390048. PMID   19757588.
  11. 1 2 3 "Gelsemine. Hazardous Substances Databank Number: 3488" (database entry). Hazardous Substances Data Bank [Internet]. Bethesda, MD: National Library of Medicine. November 8, 2002. Retrieved February 18, 2017.
  12. 1 2 3 Conroy H, Chakrabarti JK (January 1959). "NMR spectra of gelsemine derivatives. The structure and biogenesis of the alkaloid gelsemine". Tetrahedron Letters. 1 (4): 6–13. doi:10.1016/S0040-4039(01)82718-0.
  13. 1 2 3 4 Seigler DS (1998). "Indole Alkaloids" (review). Plant Secondary Metabolism. Boston, MA: Kluwer/Springer. pp. 628–654, esp. 646ff. ISBN   978-0412019814 . Retrieved February 18, 2017.
  14. ↑ "indole and ipecac alkaloid biosynthesis". qmul.ac.uk. Retrieved 19 February 2017.
  15. 1 2 Liu ZJ, Lu RR (1988). "Gelsemium Alkaloids" (review). The Alkaloids: Chemistry and Pharmacology. Vol. 33. San Diego, CA: Academic Press. pp. 84–140, esp. 132ff. ISBN   978-0080865577 . Retrieved February 18, 2017.
  16. ↑ Doyle AC (2009) [1879]. "Arthur Conan Doyle takes it to the limit (1879)". British Medical Journal. 339: b2861. doi:10.1136/bmj.b2861. S2CID   220100995.[primary source]
  17. ↑ Murray BL (1911). Kraemer H (ed.). "Correspondence: American Chemical Society, Division of Pharmaceutical Chemistry". The American Journal of Pharmacy. 83 (April): 194. Retrieved February 19, 2017.[primary source]
  18. ↑ Zhang, Jing-Yang; Gong, Nian; Huang, Jin-Lu; Guo, Ling-Chen; Wang, Yong-Xiang (2013-11). "Gelsemine, a principal alkaloid fromGelsemium sempervirensAit., exhibits potent and specific antinociception in chronic pain by acting at spinal α3 glycine receptors". PAIN. 154 (11): 2452. doi:10.1016/j.pain.2013.07.027. ISSN 0304-3959.
  19. 1 2 Venard, C.; Boujedaini, N.; Belon, P.; Mensah-Nyagan, A. G.; Patte-Mensah, C. (2008-04-22). "Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine". Neuroscience. 153 (1): 154–161. doi:10.1016/j.neuroscience.2008.02.009. ISSN 0306-4522.
  20. ↑ Lynch, Joseph W. (2004-10). "Molecular Structure and Function of the Glycine Receptor Chloride Channel". Physiological Reviews. 84 (4): 1051–1095. doi:10.1152/physrev.00042.2003. ISSN 0031-9333.
  21. ↑ Chow TY, Ng CH, Tse ML (2019-11-01). "Clinical manifestations and causes of gelsemium poisoning in Hong Kong from 2005 to 2017: Review of 33 cases". Hong Kong Journal of Emergency Medicine. 26 (6): 351–356. doi: 10.1177/1024907918808156 . ISSN   1024-9079.
  22. 1 2 3 4 Dutt V, Thakur S, Dhar VJ, Sharma A (July 2010). "The genus Gelsemium: An update". Pharmacognosy Reviews. 4 (8): 185–194. doi: 10.4103/0973-7847.70916 . PMC   3249920 . PMID   22228960.
  23. ↑ Knight A, Walter R (2001). A Guide to Plant Poisoning of Animals in North America. Manson Series. Jackson, WY: Teton NewMedia. ISBN   978-1893441118 . Retrieved February 18, 2017.[ page needed ]
  24. ↑ In the case of Bombus impatiens (bumblebees), feeding on gelsemine may reduce the load of the parasite Crithidia bombi , which, in improving bee health, increases foraging efficiency, a possible case of selective advantage of a pollinator self-medicating through collection of an otherwise generally toxic secondary metabolite. See Manson JS, Otterstatter MC, Thomson JD (January 2010). "Consumption of a nectar alkaloid reduces pathogen load in bumble bees" (PDF). Oecologia. 162 (1): 81–89. Bibcode:2010Oecol.162...81M. doi:10.1007/s00442-009-1431-9. PMID   19711104. S2CID   25322910. Archived from the original (PDF) on March 4, 2016. Retrieved February 18, 2017.[primary source]
  25. ↑ Meyer L; Boujedaini N; Patte-Mensah C; Mensah-Nyagan AG. (2013). "Pharmacological Effect of Gelsemine on Anxiety-Like Behavior in Rat". Behav Brain Res. 253 (September 15): 90–94. doi:10.1016/j.bbr.2013.07.010. PMID 23850351. S2CID 5290737
  26. ↑ Chen, Gu-Zhou; Hong, Ran (2022-10-19). "A bioinspired cyclization toward koumine and gelsemine". Cell Reports Physical Science. 3 (10): 101097. doi:10.1016/j.xcrp.2022.101097. ISSN 2666-3864.
  27. ↑ Yang, Liyan; Wang, Zhonglei. "Advances in the Total Synthesis of Gelsemine". Current Organic Chemistry. 26 (4): 356–368. doi:10.2174/1385272826666220210124835.
  28. ↑ Newcombe NJ, Ya F, Vijn RJ, Hiemstra H, Speckamp WN (1994). "The Total Synthesis of (±)-Gelsemine". Journal of the Chemical Society, Chemical Communications (6): 767–768. doi:10.1039/C39940000767.[primary source]
  29. ↑ Vijn, Robert J.; Hiemstra, Henk; Kok, Joost J.; Knotter, Martin; Speckamp, W.Nico (1987-01). "Synthetic studies towards gelsemine, I The importance of the antiperiplanar effect in the highly regioselective reduction of non-symmetrical cis-hexahydrophthalimides". Tetrahedron. 43 (21): 5019–5030. doi:10.1016/S0040-4020(01)87680-8.
  30. ↑ Dutton, Jonathan K., Robert W. Steel, Andrew S. Tasker, Velimir Popsavin, and A. Peter Johnson. "A total synthesis of gelsemine: oxindole spiroannelation." Journal of the Chemical Society, Chemical Communications 6 (1994): 765-766.
  31. ↑ Fukuyama, Tohru; Liu, Gang (1996-01-01). "Stereocontrolled Total Synthesis of (±)-Gelsemine". Journal of the American Chemical Society. 118 (31): 7426–7427. doi:10.1021/ja961701s. ISSN 0002-7863.
  32. ↑ S. Yokoshima, H. Tokuyama, T. Fukuyama Angew. Chem. Int. Ed., 39 (2000), pp. 4073-4075
  33. ↑ Atarashi, Shogo; Choi, Joong-Kwon; Ha, Deok-Chan; Hart, David J.; Kuzmich, Daniel; Lee, Chih-Shone; Ramesh, Subban; Wu, Shung C. (1997-07-01). "Free Radical Cyclizations in Alkaloid Total Synthesis: (±)-21-Oxogelsemine and (±)-Gelsemine". Journal of the American Chemical Society. 119 (27): 6226–6241. doi:10.1021/ja970089h. ISSN 0002-7863.
  34. ↑ Earley, William G.; Jacobsen, Jon E.; Madin, Andrew; Meier, G. Patrick; O'Donnell, Christopher J.; Oh, Taeboem; Old, David W.; Overman, Larry E.; Sharp, Matthew J. (2005-12-01). "Aza-Cope Rearrangement−Mannich Cyclizations for the Formation of Complex Tricyclic Amines: Stereocontrolled Total Synthesis of (±)-Gelsemine". Journal of the American Chemical Society. 127 (51): 18046–18053. doi:10.1021/ja055710p. ISSN 0002-7863. PMC 2570375. PMID 16366556.
  35. ↑ Ng, Fay W.; Lin, Hong; Danishefsky, Samuel J. (2002-08-01). "Explorations in Organic Chemistry Leading to the Total Synthesis of (±)-Gelsemine". Journal of the American Chemical Society. 124 (33): 9812–9824. doi:10.1021/ja0204675. ISSN 0002-7863.
  36. ↑ Zhou, Xuan; Xiao, Tao; Iwama, Yusuke; Qin, Yong (2012-05-14). "Biomimetic Total Synthesis of (+)-Gelsemine". Angewandte Chemie International Edition. 51 (20): 4909–4912. doi:10.1002/anie.201201736.
  37. ↑ Lam, Jonathan K.; Joseph, Scott B.; Vanderwal, Christopher D. (2015-06-03). "A Zincke aldehyde approach to gelsemine". Tetrahedron Letters. Memorial Symposium-in-Print for Harry Wasserman. 56 (23): 3165–3168. doi:10.1016/j.tetlet.2014.12.089.
  38. ↑ Chirumbolo S (2011). "Gelsemine and Gelsemium sempervirens L. Extracts in Animal Behavioral Test: Comments and Related Biases". Frontiers in Neurology. 2 (May 16): 31. doi: 10.3389/fneur.2011.00031 . PMC   3098419 . PMID   21647210.
  39. ↑ Meyer L, Boujedaini N, Patte-Mensah C, Mensah-Nyagan AG (September 2013). "Pharmacological effect of gelsemine on anxiety-like behavior in rat". Behavioural Brain Research. 253 (September 15): 90–94. doi:10.1016/j.bbr.2013.07.010. PMID   23850351. S2CID   5290737.[primary source]
  40. 1 2 3 Lin L, Zheng J, Zhu W, Jia N (March 2015). "Nephroprotective effect of gelsemine against cisplatin-induced toxicity is mediated via attenuation of oxidative stress". Cell Biochemistry and Biophysics. 71 (2): 535–541. doi:10.1007/s12013-014-0231-y. PMID   25343941. S2CID   16724810.[primary source]
  41. ↑ Wu T, Chen G, Chen X, Wang Q, Wang G (January 2015). "Anti-hyperlipidemic and anti-oxidative effects of gelsemine in high-fat-diet-fed rabbits". Cell Biochemistry and Biophysics. 71 (1): 337–344. doi:10.1007/s12013-014-0203-2. PMID   25213292. S2CID   9777283.[primary source]
  42. ↑ Winterburn GW (1883). "Gelsemium sempervirens". Transactions of the National Eclectic Medical Association. 10.[primary source]
  43. ↑ Christie A (1927). The Big Four. Glasgow, GBR: William Collins & Sons.[ page needed ]
  44. ↑ Eirik (30 October 2013). "Investigating Agatha Christie's Poirot: Episode-by-episode: The Big Four". investigatingpoirot.blogspot.com. Retrieved 19 February 2017.
  45. ↑ "House of Cards (2013) s05e12". 2013.
  46. ↑ "iZombie (2015) s03e09 Episode Script". 2015.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.