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"Liu, Zhao-Ying"
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China Medicinal Plants of the Ampelopsis grossedentata—A Review of Their Botanical Characteristics, Use, Phytochemistry, Active Pharmacological Components, and Toxicology
Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.
Journal Article
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.
Journal Article
Hypoxia tolerance determine differential gelsenicine-induced neurotoxicity between pig and mouse
Background
Gelsemium elegans
(
G. elegans
) is widely recognized as one of the most toxic plants globally, particularly harmful to humans. Some reports indicate that it is non-toxic to pigs and even has a growth-promoting effect; however, the underlying reasons for this paradox remain unclear.
Methods
Gelsenicine is the main toxic component of
G. elegans
. This study characterized gelsenicine-induced toxicity using electrophysiological recordings, molecular dynamic simulations, c-Fos immunostaining, and multi-omics technologies. Additionally, we conducted a comprehensive analysis comparing the toxic effects of gelsenicine across various animal species through examinations of tissue distribution, blood gas analysis, metabonomics, and behavioral tests.
Results
We demonstrated that gelsenicine-induced hypoxia leads to respiratory depression in mice by enhancing the effect of gamma-aminobutyric acid (GABA) on GABA receptors (GABARs). Glycine significantly ameliorated hypoxia and improved the survival of gelsenicine-poisoned mice. Under gelsenicine-induced hypoxic conditions, N-methyl-D-aspartate (NMDA) receptor function and mitochondrial energy metabolism processes were perturbed, resulting in neuronal excitotoxicity. Finally, we confirmed that pigs could tolerate hypoxia and were resistant to gelsenicine toxicity due to high concentrations of circulating glycine and low levels of NMDA receptors (NMDARs) in the hippocampus.
Conclusions
These findings suggest that hypoxic protection should be considered as a potential therapeutic strategy for gelsenicine poisoning. Our study contributes to preventing potential risks posed by
G. elegans
poisoning to human and animal health.
Graphical Abstract
Journal Article
A novel two-dimensional liquid chromatography system for the simultaneous determination of three monoterpene indole alkaloids in biological matrices
The present paper describes a novel two-dimensional liquid chromatography (2D-LC) system, which is comprised of a first-dimensional ion exchange chromatography (IEX1) column, trap column, and second-dimensional reversed-phase chromatography (RP2) column system. The biological sample is separated by the first-dimensional LC using an IEX column to remove interferences. The analytes are transferred to the trap column after heart-cutting. Then, the analytes are transferred to the second-dimensional LC using an RP2 column for further separation and ultraviolet detection. This 2D-LC system can offer a large injection volume to provide sufficient sensitivity and exhibits a strong capacity for removing interferences. Here, the determination of three monoterpene indole alkaloids (MIAs; gelsemine, koumine, and humantenmine) from Gelsemium in biological matrices (plasma, tissue, and urine) was used this 2D-LC system. After a rapid and easy sample preparation method based on protein precipitation, the sample was injected into the 2D-LC. The method was developed and validated in terms of the selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The sample preparation time for the three MIAs was 15 min. The LOD for these compounds was 10 ng/mL, which was lower than the developed HPLC methods. The results showed that this method had good quantitation performance and allowed the determination of gelsemine, koumine, and humantenmine in biological matrices. The method is rapid, exhibits high selectivity, has good sensitivity, and is low-cost, thus making it well-suited for application in the pharmaceutical and toxicological analysis of Gelsemium.
Journal Article
Biotransformation and tissue distribution of protopine and allocryptopine and effects of Plume Poppy Total Alkaloid on liver drug-metabolizing enzymes
In this study, the biotransformation in the plasma, urine and feces of rats following oral administration of protopine (PRO) and allocryptopine (ALL)were explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of tissues was developed and applied to the tissue distribution study in rats following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks. A total of ten PRO metabolites and ten ALL metabolites were characterized in rats
in vivo
. Among these metabolites, six PRO metabolites and five ALL metabolites were reported for the first time. The predicated metabolic pathways including ring cleavage, demethylation following ring cleavage, and glucuronidation were proposed. The low-concentration residue of PRO and ALL in various tissues was detected at 24 h and 48 h after dosing, which indicated that both compounds could be widely distributed in tissues and exist as low levels of residue. The activities of erythromycin N-demethylase, aminopyrine N-demethylase and NAD (P)H quinone oxidoreductase in female rats can be induced post-dose, but these activities were inhibited in male rats. The proposed biotransformation and residues of PRO and ALL and their effects on enzymes may provide a basis for clarifying the metabolism and interpreting pharmacokinetics.
Journal Article
Security of a kind of quantum secret sharing with entangled states
We present a new collusion attack to a kind of quantum secret sharing schemes with entangled states. Using this attack, an unauthorized set of agents can gain access to the shared secret without the others’ cooperation. Furthermore, we establish a general model for this kind of quantum secret sharing schemes and then give some necessary conditions to design a secure quantum secret sharing scheme under this model.
Journal Article
The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells
Two optical isomers, +/− gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (1H-1H COSY, HMBC, HSQC) NMR spectroscopy and high-resolution mass spectrometry (HRMS). The isolated alkaloids were tested in vitro for cytotoxic potential against PC12 cells by the MTT assay. As a result, (+) gelsemine (compound 1) exhibited cytotoxic activity against PC12 cells with an IC50 value of 31.59 μM, while (−) gelsemine (compound 2) was not cytotoxic.
Journal Article
Two-Dimensional Liquid Chromatography Method for the Determination of Gelsemium Alkaloids in Honey
Toxic Chinese medicine residues in honey pose a serious threat to consumer health. Gelsemium is one of the nine ancient poisons, making the whole plant virulent. The residue of Gelsemium alkaloid in honey causes poisoning from time to time. Therefore, it is very important to establish a method for the detection of Gelsemium alkaloids in honey. In this study, a method of solid phase extraction (SPE) with two-dimensional liquid chromatography (2D-LC) was developed for the first time for the simultaneous determination of Gelsemium alkaloids in honey, including gelsemine, koumine and humantenmine. First, the honey samples were purified by a PRS cation exchange column and extracted with 5% ammoniated methanol. Then, we verified the methodological indicators, which were in line with the Codex Guideline requirements. The verification results are as follows: matrix-matched calibrations indicated that the correlation coefficients were higher than 0.998. The recovery was in the range of 81%–94.2% with an intraday precision (RSD) of ≤5.0% and interday RSD of ≤3.8%. The limit of detection for the three alkaloids was 2 ng/g. The limits of quantification for gelsemine and koumine were 5 ng/g, and humantenmine was 20 ng/g. This method can be applied to the monitoring of Gelsemium alkaloids in honey.
Journal Article
The multicomponent residue depletion of Gelsemium elegans in pig tissues, urine, and plasma
(
) as a traditional medicinal plant used in livestock production. The use of
in veterinary clinics may pose safety risks to human health.
The aim of this study was to investigate tissue residue depletion in pigs fed
powder.
A precise quantitation method and a simultaneous semi-quantitation method for multiple components independently of standards in pig tissues were developed for the first time. The two methods were validated in terms of specificity, LODs, LOQs, linearity, accuracy, precision, and matrix effects. They were then applied to a tissue residue depletion study after
powder at a dose of 2% per kg feed were fed to pigs.
Compared with precise quantitation, the method validation results indicated that the semi-quantitation method was reliable and acceptable for multicomponent quantification independent of standards. Many
alkaloids are widely distributed in most tissues of pigs. Tissue residue depletion studies indicated that 14-hydroxygelsenicine, 11-hydroxygelsenicine, and gelsemoxonine could be used as potential residue markers, and pancreas, small intestine, and lung tissues could be considered as potential residue target tissues of
. In addition, both urine and plasma could be used to predict 14-hydroxygelsenicine and gelsemoxonine residues in the liver, pancreas, and small intestinal tissues of pigs.
The developed semi-quantification method can be applied to monitor the application and residue of
. The results provide scientific evidence for evaluating the safety of animal-derived food from
for consumers and will be helpful for its application and future development.
Journal Article