摘要：
This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome's functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function. IMPORTANCE: Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.
摘要：
Pseudorabies virus (PRV), an α-herpesvirus, induces immunosuppression and can lead to severe neurological diseases. N-methyl-D-aspartate receptor (NMDAR), an important excitatory nerve receptor in the central nervous system, is linked to various nervous system pathologies. The link between NMDAR and PRV-induced neurological diseases has not been studied. In vivo studies revealed that PRV infection triggers a reduction in hippocampal NMDAR expression, mediated by inflammatory processes. Extensive hippocampal neuronal degeneration was found in mice on the 6th day by hematoxylin-eosin staining, which was strongly correlated with increased NMDAR protein expression. In vitro studies utilizing the CCK-8 assay demonstrated that treatment with an NMDAR antagonist significantly heightened the cytotoxic effects of PRV on T lymphocytes. Notably, NMDAR inhibition did not affect the replication ability of PRV. However, it facilitated the accumulation of pro-inflammatory cytokines in PRV-infected T cells and enhanced the transcription of the CD25 gene through the secretion of interleukin-2 (IL-2), consequently exacerbating immunosuppression. In this study, we found that NMDAR has functional activity in T lymphocytes and is crucial for the inflammatory and immune responses triggered by PRV infection. These discoveries highlight the significant role of NMDAR in PRV-induced neurological disease pathogenesis.
摘要：
<jats:sec>
<jats:title>Aim:</jats:title>
<jats:p>The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig,
goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium
alkaloids among different species.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>A human, goat, pig and rat liver microparticles were incubated in vitro. After incubating at 37°C for
1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol
extract of Gelsemium elegans and its metabolites.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13
metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine,
yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and
dehydrogenation. After preliminary identification, the metabolites detected in the four species were different.
All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids
were detected in goat and human microsomes.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion:</jats:title>
<jats:p>In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in
vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development
and rational application.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>result:</jats:title>
<jats:p>46 natural products were characterized from alcohol extract of Gelsemium elegan and 13 metabolites were identified. The metabolic pathways included oxidation， demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. all 13 metabolites were detected in pig and rat, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human.</jats:p>
</jats:sec>
摘要：
Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5 min after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20 min. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.
摘要：
We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gelsemium elegans (G. elegans) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/n-hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine (1, 12.1 mg), sempervirine (2, 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine (3, 10.1 mg), koumine (4, 50.5 mg), gelsemine (5, 32.2 mg), gelselvirine (6, 50.5 mg), and 11-hydroxyhumanmantenine (7, 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans, holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines.
通讯机构：
[Zhao-Ying Liu; Yong Wu] A;Authors to whom correspondence should be addressed.<&wdkj&>College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China
关键词：
alkaloid;gelsemium elegan;iridoid;koumine;plant extract;unclassified drug;absorption;animal experiment;animal model;animal tissue;Article;blood sampling;controlled study;drug distribution;excretion;female;Gelsemium;high performance liquid chromatography;in vivo study;intestine blood flow;kidney tissue;male;metabolite;nonhuman;rat;relative humidity;sex difference;time of flight mass spectrometry;urine sampling
摘要：
Currently, the identification of herb metabolites is challenging due to a lack of clear standards. Here, using Gelsemium as an example, we present a protocol for characterizing target components of herbs. This approach utilizes high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry guided by an in-house herb metabolite database based on reported studies and mass spectrometry. We describe steps for creating an in-house database, preparing and detecting samples, processing data, and characterizing compounds. This approach offers a reference for future research on the identification of herb metabolites. For complete details on the use and execution of this protocol, please refer to Liu etal. (2017).(1).
摘要：
<jats:sec><jats:title>Introduction</jats:title><jats:p><jats:italic>Gelsemium elegans</jats:italic> (<jats:italic>G. elegans</jats:italic>) as a traditional medicinal plant used in livestock production. The use of <jats:italic>G. elegans</jats:italic> in veterinary clinics may pose safety risks to human health.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>The aim of this study was to investigate tissue residue depletion in pigs fed <jats:italic>G. elegans</jats:italic> powder.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>G. elegans</jats:italic> powder at a dose of 2% per kg feed were fed to pigs.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>G. elegans</jats:italic> 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 <jats:italic>G. elegans</jats:italic>. 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The developed semi-quantification method can be applied to monitor the application and residue of <jats:italic>G. elegans</jats:italic>. The results provide scientific evidence for evaluating the safety of animal-derived food from <jats:italic>G. elegans</jats:italic> for consumers and will be helpful for its application and future development.</jats:p></jats:sec>
作者机构：
College of Veterinary Medicine Hunan Agricultural University Changsha Hunan China;Hunan Engineering Technology Research Center of Veterinary Drugs Hunan Agricultural University Changsha Hunan China;[Jiangyu Long; Mohuan Tang; Mengting Zuo; Wenbo Xu; Siyu Meng; Zhaoying Liu] College of Veterinary Medicine Hunan Agricultural University Changsha Hunan China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs Hunan Agricultural University Changsha Hunan China
摘要：
<jats:title>Abstract</jats:title><jats:p>The genus <jats:italic>Gelsemium</jats:italic> belongs to the family Loganiaceae, one of the traditional Chinese herbs. <jats:italic>Gelsemium</jats:italic> 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 <jats:italic>γ</jats:italic>‐aminobutyric acid type A receptor (GABA<jats:sub>A</jats:sub>R), 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 <jats:italic>Gelsemium</jats:italic> in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of <jats:italic>Gelsemium</jats:italic> as a therapeutic drug for anxiety‐related diseases.</jats:p>
通讯机构：
[Zhao-Ying Liu; Qi Tang] A;Authors to whom correspondence should be addressed.<&wdkj&>College of Horticulture, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China
通讯机构：
[Zhao-Ying Liu] C;College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
Gelsemium elegans (G.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. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 mu g/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyR alpha 3 and Gephyrin. The PGE2 model group showed decreased expression levels of GlyR alpha 3 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 GlyR alpha 3 and Gephyrin, which are key targets of the Gly receptor pathway.
作者机构：
[Wang, Zi-Yuan; Qi, Xue-Jia; Liu, Zhao-Ying; Ma, Xiao; Zuo, Meng-Ting] Hunan Agr Univ, Coll Vet Med, Changsha 410128, Peoples R China.;[Wang, Zi-Yuan; Qi, Xue-Jia; Liu, Zhao-Ying; Ma, Xiao; Zuo, Meng-Ting] Hunan Agr Univ, Hunan Engn Technol Res Ctr Vet Drugs, Changsha 410128, Peoples R China.
通讯机构：
[Zhao-Ying Liu] C;College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Author to whom correspondence should be addressed.
通讯机构：
[Zhao-Ying Liu; Zhao-Ying Liu Zhao-Ying Liu Zhao-Ying Liu] C;College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha, Hunan, China
摘要：
<jats:sec><jats:title>Rationale</jats:title><jats:p>Rankinidine belongs to the humantenine‐type alkaloids isolated from <jats:italic>Gelsemium</jats:italic>. Currently, the mechanism behind the toxicity differences of rankinidine has not been explained. In this study, our purpose was to elucidate the major <jats:italic>in vitro</jats:italic> metabolic pathways of rankinidine and to compare the formation of metabolites of rankinidine in human (HLMs), rat (RLMs), goat (GLMs) and pig (PLMs) liver microsomes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This is the first study to compare the <jats:italic>in vitro</jats:italic> metabolism of rankinidine with high‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (LC/QTOF). The MS/MS data and LC/MS peak area acquired in positive ion mode were used to analyze metabolite structures and compare metabolism.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified 11 metabolites (M1–M11) in total and found five main metabolic pathways, consisting of demethylation (M1), reduction (M2), oxidation at different positions (M3–M5), oxidation and reduction (M6–M10) and demethylation and oxidation (M11). The metabolism of rankinidine has qualitative and quantitative species‐specific differences <jats:italic>in vitro</jats:italic>. In PLMs and GLMs, the main metabolic pathway of rankinidine was oxidation. Notably, among the four species, the oxidation ability of rankinidine was highest in pigs and goats, and the demethylation and reduction abilities of rankinidine were highest in humans and rats.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The interspecific metabolic differences of rankinidine in HLMs, PLMs, GLMs and RLMs were compared and studied for the first time using LC/QTOF. These findings will certainly support future studies of rankinidine metabolism <jats:italic>in vivo</jats:italic> and will contribute to elucidating the cause of species‐specific differences behind <jats:italic>Gelsemium</jats:italic> toxicity.</jats:p></jats:sec>
