Gelsemium Research Articles

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

AbstractThe genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha‐hydroxysteroid oxidoreductase (3α‐HSOR) expression. The latter can activate the excitation‐inhibitory response via the γ‐aminobutyric acid type A receptor (GABAAR), reduce the abnormal corticotropin‐releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety‐related neural circuits. Gelsemine also inhibited the overexpression of brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety‐related diseases.

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

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.

Phosphoproteomics reveals NMDA receptor-mediated excitotoxicity as a key signaling pathway in the toxicity of gelsenicine

Gelsenicine is one of the most toxic compounds in the genus Gelsemium, but the mechanism of toxicity is not clear. In this paper, tandem mass tag quantitative phosphoproteomics was used to study the changes in protein phosphorylation in different brain regions at different time points after gelsenicine poisoning in mice. The correlation between neurotransmitter receptors and the toxicity of gelsenicine was analyzed by molecular docking and rescue experiments. Parallel reaction monitoring (PRM) was used to verify the related proteins. A total of 17877 unique phosphosites were quantified and mapped to 4170 brain proteins to understand the signaling pathways. Phosphoproteomics revealed gelsenicine poisoning mainly affected protein phosphorylation levels in the hippocampus, and through bioinformatics analysis, it was found gelsenicine poisoning significantly affected neurotransmitter synaptic pathway. The molecular docking results showed that gelsenicine could bind to the N-methyl-D-aspartic acid receptor (NMDAR). In addition, we found that NMDA was effective in improving the survival rate of the animals tested, and this effect was associated with reduced protein phosphorylation by PRM validation. The results revealed that gelsenicine affects neurotransmitter release and receptor function. This is the first demonstration that NMDA receptor-mediated excitotoxicity is a key signaling pathway in the toxicity of gelsenicine.

Isolation and Identification of a Potent PTP1B Inhibitor, Ursolic Acid, from Carolina Jasmine (Gelsemium sempervirens (L.) J.St.-Hil.)

Extracts of Carolina jasmine (Gelsemium sempervirens (L.) J.St.-Hil.) petals were evaluated in vitro for inhibition activity against protein tyrosine phosphatase 1B (PTP1B). The principle active agent was also isolated from the extract and identified as ursolic acid (1). This is the first report of ursolic acid from G. sempervirens and of PTP1B-inhibiting activity in the genus Gelsemium.

Toxicokinetics of 11 Gelsemium Alkaloids in Rats by UPLC-MS/MS.

Gelsemium elegans (Gardn. & Champ.) Benth. is a plant belonging to the genus Gelsemium (family Gelsemiaceae), and its main components are alkaloids. It is a Chinese traditional medicinal plant and notoriously known as a highly toxic medicine. However, a method has not yet been found for the simultaneous detection of 11 Gelsemium alkaloids in rat plasma, and the toxicokinetics of 11 Gelsemium alkaloids after intravenous administration has not been reported. In this work, we have developed a sensitive and rapid method of ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) for the detection of 11 Gelsemium alkaloids in rat plasma. The toxicokinetic behavior was also investigated, so as to provide a reference of the scientific properties of Gelsemium elegans and improve the efficacy and safety of drugs. Sixty-six Sprague-Dawley rats were randomly divided into 11 groups, six rats in each group. Each group was intravenously given one alkaloid (0.1 mg/kg), respectively. A Waters UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm) was used for chromatographic separation. Methanol and water (containing 0.1% formic acid) were used for the mobile phase with gradient elution. Multiple reactions were monitored, and positive electrospray ionization was used for quantitative analysis. The precision was less than 16%, and the accuracy was between 86.9% and 113.2%. The extraction efficiency was better than 75.8%, and the matrix effects ranged from 88.5% to 107.8%. The calibration curves were in the range of 0.1–200 ng/mL, with a correlation coefficient (R2) greater than 0.995. The UPLC-MS/MS method was successfully applied to the toxicokinetics of 11 Gelsemium alkaloids in rats after intravenous administration (0.1 mg/kg for each alkaloid). The results of the toxicokinetics provide a basis for the pharmacology and toxicology of Gelsemium alkaloids and scientific evidence for the clinical use of Gelsemium alkaloids.

Gene expression and highly diluted molecules.

Gene expression and highly diluted molecules.

Bisindole Alkaloids with Neural Anti-inflammatory Activity from Gelsemium elegans

Three new trace bisindole alkaloids geleganimines A and B (1, 2) and geleganamide (3) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by spectroscopy, particularly from their carbon-proton coupling constants, and electronic circular dichroism. Compounds 1-3 are the first bisindole alkaloids discovered from the genus Gelsemium. Geleganimine B exhibited anti-inflammatory activity indirectly by suppressing lipopolysaccharide-induced pro-inflammatory factors in BV2 microglial cells with an IC50 value of 10.2 μM. These findings confirm the importance of bioactive trace components in medicinal plant research.

Three novel β-carboline alkaloids from Gelsemium elegans

Three novel β-carboline alkaloids characterized with a unique degraded monoterpenoid moiety, gelebolines A–C (1–3), together with 11 known alkaloids of different types, were isolated from the roots of Gelsemium elegans. The structures of new alkaloids were established on the basis of analysis of spectroscopic data. It is the first example for report of β-carboline from genus Gelsemium (Loganiaceae).

The Relationship Between Soil Environmental Factors and Flowering Phenology in Two Sympatric Southeastern Gelsemium Species—Does Habitat Specialization Determine Differences in Flowering Time?

Abstract Previous research has found significant differences in flowering time between sympatric, non-hybridizing populations of congeners in the genus Gelsemium (Gelsemium sempervirens and G. rankinii). An experimental approach using a common garden, reciprocal transplant experiments, and observations of natural populations were used to test the hypothesis that soil environmental variables (soil moisture and soil temperature) related to habitat specificity of the two species influence differences in flowering phenology. Replicated pairs of both species were planted into a common garden and into wet and dry habitats that typify the two species (dry for earlier flowering G. sempervirens and wet for later flowering G. rankinii). Two sites with sympatric natural populations of both species were also studied for comparison. The number of open flowers was counted every two weeks in 2007 and 2008 in all sites and in 2009 for the reciprocal transplant experiment. Soil moisture and soil temperature varied by site...

Chemical constituents of aerial parts of Gelsemium elegans

To study the chemical constituents from the aerial parts of Gelsemium elegans. Compounds were isolated and purified by repeated column chromatography, as well as semiprep arative HPLC, and their structures were identified by physicochemical properties and spectroscopic methods, such as NMR and MS. Sixteen compounds were obtained and identified from G. elegans, including nine alkaloids: koumine (1), gelsenicine (2), 19-(Z)-akuammidine (3), gelsemoxonine(4), gelsemin (5), gelsevirine (6), humantenine (7), 11-methoxygelsemamide (8) and gelegamine D (9). Three megastigmane glycosides: (3R, 5S, 6S, 7E, 9R)-megastigman-7-ene-3, 5, 6, 9-tetrol-9-O-beta-D-glucopyranoside (10), (6R, 7E, 9R)-9-hydroxy-4, 7-megastigmadien-3-one-9-O-[alpha-L-arabinopyranosyl-(1 --> 6)-beta-D-glucopyranoside] (11) and (6S, 7E, 9R) -6, 9-dihydroxy-4, 7-megastigmadien-3-one-9-O-[alpha-L-arabinopyranosyl-(1 --> 6) -beta-D-glucopyranoside] (12). Two flavone C-glycosides: orientin (13) and isorientin (14); one iridoid glycoside, sweroside (15) and one fructoside, n-butyl-alpha-D-fructofuranoside (16). Compounds 10-16 were isolated from the genus Gelsemium for the first time.

Gelsemine and Gelsemium sempervirens L. Extracts in Animal Behavioral Test: Comments and Related Biases

GENERAL COMMENTARY article Front. Neurol., 16 May 2011 | https://doi.org/10.3389/fneur.2011.00031

The genus Gelsemium: An update.

The review includes 103 references on the genus Gelsemium, and comprises ethnopharmacology, morphology, phytoconstituents, pharmacological reports, clinical studies and toxicology of the prominent species of Gelsemium. Alkaloids and iridoids constitute major classes of phytoconstituents of the genus. Most popular species of the genus are the Asian G. elegans and the two North American related species, G. sempervirens and G. rankinii. Gelsemium species are categorized under medicinal as well as poisonous plants. Amongst various species, G. elegans and G. sempervirens possess medicinal value, and have been traditionally used as nervous system relaxant. These plants have been explored exhaustively for their anticancer activity. In the concluding part, the future scope of Gelsemium species has been emphasized with a view to establish their multifarious biological activities and mode of actions

The Alkaloids of Chinese Gelsemium, Kou Wen1

The Alkaloids of Chinese Gelsemium, Kou Wen¹

Third Alkaloid from Gelsemium

Third Alkaloid from Gelsemium

Poisoning by Gelsemium

Poisoning by Gelsemium