Seven New Monoterpenoid Indole Alkaloids from Gelsemium elegans

Seven new indole alkaloids were isolated from the roots of Gelsemium elegans Benth. and their structures were determined by spectroscopic analysis and chemical transformation from known alkaloids. Kounaminal ( 1 ) is a new koumine‐type alkaloid that contains an unusual aminal moiety. Humantenoxenine ( 2 ) and 15‐hydroxyhumantenoxenine ( 3 ) are humantenine‐type alkaloids that contain a novel β‐amino‐α,β‐unsaturated ketone residue. The other four novel alkaloids are two gelsedilam‐related and two gelsenicine‐related alkaloids.     

Comprehensive identification and structural characterization of target components from Gelsemium elegans by high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry based on accurate mass databases combined with MS/MS spectra

This study reports an applicable analytical strategy of comprehensive identification and structure characterization of target components from Gelsemium elegans by using high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QqTOF MS) based on the use of accurate mass databases combined with MS/MS spectra. The databases created included accurate masses and elemental compositions of 204 components from Gelsemium and their structural data. The accurate MS and MS/MS spectra were acquired through data‐dependent auto MS/MS mode followed by an extraction of the potential compounds from the LC‐QqTOF MS raw data of the sample. The same was matched using the databases to search for targeted components in the sample. The structures for detected components were tentatively characterized by manually interpreting the accurate MS/MS spectra for the first time. A total of 57 components have been successfully detected and structurally characterized from the crude extracts of G. elegans , but has failed to differentiate some isomers. This analytical strategy is generic and efficient, avoids isolation and purification procedures, enables a comprehensive structure characterization of target components of Gelsemium and would be widely applicable for complicated mixtures that are derived from Gelsemium preparations. Copyright © 2017 John Wiley & Sons, Ltd.     

Two new benzofuran lignan glycosides from Gelsemium elegans

Two new benzofuran lignan glycosides, gelsemiunoside A and B, were isolated from the whole plant of Gelsemium elegans Benth. Their structures were elucidated on the basis of spectroscopic evidence. Furthermore, gelsemiunoside A and B were shown a potent cytotoxic activity by suppressing the proliferation of A375-S2 cells.     

Two New Megastigmane Glycosides and a New Iridoid Glycoside from Gelsemium elegans

Two new megastigmane glycosides, eleganosides A and B ( 1 and 3 , resp.), and one new iridoid glycoside, gouwenoside A ( 4 ), together with two known compounds, foliasalacioside B₁ ( 2 ) and loganin ( 5 ), were isolated from the aerial parts of Gelsemium elegans (Gardn. et Champ.) Benth. (Loganiaceae). Their structures were elucidated by spectroscopic methods including 1D‐ and 2D‐NMR techniques. The absolute configuration of 1 was determined by CD spectroscopy.     

Two New 11‐Hydroxy‐Substituted Gelsedine‐Type Indole Alkaloids from the Stems of Gelsemium elegans

Two new 11‐hydroxy‐substituted gelsedine‐type indole alkaloids, named 11,14‐dihydroxygelsenicine ( 1 ) and 11‐hydroxygelsenicine ( 2 ), together with six known alkaloids, i.e., koumine, gelsemine, 14‐hydroxygelsenicine, 11‐hydroxyhumantenine, gelsenicine, and (19Z)‐akuammidine, were isolated from the EtOH extract of the stems of Gelsemium elegans Benth. Their structures were determined mainly by means of spectroscopic analyses including HR‐ESI‐MS and 2D‐NMR (HSQC, HMBC, ¹H,¹H‐COSY). The configuration of 1 was confirmed by X‐ray‐diffraction analysis.     

Simultaneous determination of gelsemine and koumine in rat plasma by UPLC‐MS/MS and application to pharmacokinetic study after oral administration of Gelsemium elegans Benth extract

A simple, rapid and sensitive method using UPLC‐MS/MS was established and validated for simultaneous determination of gelsemine and koumine in rat plasma after oral administration of Gelsemium elegans Benth extract. Plasma was performed with methanol precipitation and berberine was chosen as the internal standard. Plasma samples were separated on an Acquity UPLC® BEH C₁₈ column (3.0 × 50 mm, 1.7 μm) with gradient elution using acetonitrile and 0.1% formic acid aqueous solution as the mobile phase at a flow rate of 0.4 mL/min. Multiple reaction monitoring mode in positive ion mode was utilized for detection. The calibration curves were linear over the range of 0.2–100 ng/mL for gelsemine and 0.1–50 ng/mL for koumine, with the lower limits of quantification 0.2 and 0.1 ng/mL, respectively. The intra‐ and inter‐precision and accuracy were well within the acceptable ranges. The developed method was successfully applied to an in vivo pharmacokinetic study in rat after oral administration of 10 mg/kg Gelsemium elegans Benth extract.     

Six new monoterpenoid indole alkaloids from the aerial part of Gelsemium elegans

Six new monoterpenoid indole alkaloids along with four known analogues were isolated from the aerial part of Gelsemium elegans. Their structures with absolute configurations were elucidated by NMR, HRESIMS, X-ray diffraction, CD spectra, and molecular modeling calculation. Among them, gelselenidine (1) is a new gelsedine-type alkaloid with a 2,3-epoxybutane unit. Gelseziridine (2) is the first example of monoterpenoid indole alkaloids with an oxaziridine residue. Compounds 6 and 7 are a pair of N₄ epimers of humantenine N₄-oxide. A plausible biogenetic pathway for compounds 1-4 was also proposed.     

Preparative separation of alkaloids from Gelsemium elegans Benth. using pH-zone-refining counter-current chromatography

Alkaloids in Gelsemium elegans possess a variety of therapeutic properties, including tumor suppression, analgesic and anti-inflammatory effects. In China, G. elegans has been used for centuries to treat a variety of medical conditions, including chronic pain and skin ulcer. Methods currently used to separate the active components of G. elegans are time-consuming and have low recovery. In the present study, we used pH-zone-refining counter-current chromatography to separate major alkaloids from a crude extract of G. elegans. The two-phase solvent system was methyl tert-butyl ether (MtBE)/acetonitrile/water (3:1.5:4, v/v). Triethylamine (20 mM) was added to the upper organic stationary phase as a retainer. Hydrochloric acid (10 mM) was added to the lower aqueous phase as an eluter. From 1.5 g of crude extract, we obtained 312 mg gelsemine, 420 mg koumine and 195 mg gelsevirine, with purities at 94.8%, 95.9% and 96.7%, respectively, which were determined by HPLC at 256 nm. The chemical identity of the isolated compounds was verified by electrospray ionization-mass spectrometry (ESI-MS), 1H NMR and 13C NMR. These results demonstrated that pH-zone-refining counter-current chromatography is an effective method to separate and purify major alkaloids from G. elegans.     

Excretion,Metabolism, and Tissue Distribution of Gelsemium elegans (Gardn. & Champ.) Benth in Pigs

Gelsemium elegans (Gardn. & Champ.) Benth is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of G. elegans restricts its development and clinical applications, but in veterinary applications, G. elegans has been fed to pigs as a feed additive without poisoning. However, until now, the in vivo processes of the multiple components of G. elegans have not been studied. This study investigates the excretion, metabolism and tissue distribution of the multiple components of G. elegans after feeding it to pigs in medicated feed. Pigs were fed 2% G. elegans powder in feed for 45 days. The plasma, urine, bile, feces and tissues (heart, liver, lung, spleen, brain, spinal cord, adrenal gland, testis, thigh muscle, abdominal muscle and back muscle) were collected 6 h after the last feeding and analyzed using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Five natural products in plasma, twelve natural products and five metabolites in urine, and three natural products in feces were characterized, suggesting that multiple components from G. elegans were excreted in the urine. However, ten natural products and four metabolites were detected in bile samples, which suggested that G. elegans is involved in enterohepatic circulation in pigs. A total of seven of these metabolites were characterized, and four metabolites were glucuronidated metabolites. Ten natural products and six metabolites were detected in the tissues, which indicates that G. elegans is widely distributed in tissues and can cross the blood-brain barrier. Among the characterized compounds, a highly toxic gelsedine-type alkaloid from G. elegans was the main compound detected in all biological samples. This is the first study of the excretion, metabolism and tissue distribution of multiple components from G. elegans in pigs. These data can provide an important reference to explain the efficacy and toxicity of G. elegans. Additionally, the results of the tissue distribution of G. elegans are of great value for further residue depletion studies and safety evaluations of products of animals fed G. elegans.     

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.