Gelsemine is an active principle and a major alkaloid found in Gelsemium genus of plants belonging to the Loganiaceae family. The aim of the present study was to explore whether gelsemine exerts anxiolytic effects on a mouse model of chronic-unpredictable-mild-stress (CUMS)-induced anxiety-like behaviors. NOD-like receptor protein 3 (NLRP3) inflammasome, downregulated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were also evaluated as potential mechanisms. First, gelsemine reversed a CUMS-induced decrease in body-weight gain in mice. Next, gelsemine alleviated CUMS-induced anxiety-like behaviors, as evidenced by the increased distance traveled in the central zone of the open-field test, both the increased percentage of time spent and distance traveled in the light compartment, the increased number of transitions between compartments in the light/dark-transition test, and the increased percentage of entries and time spent in the open arm of the elevated plus-maze. In addition, gelsemine decreased the levels of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, in the hypothalamus and hippocampus of CUMS mice. Interestingly, further investigations revealed that gelsemine inhibited the CUMS-induced activation of NLRP3-inflammasome pathways and downregulated CREB and BDNF overexpression in the hypothalamus. In summary, gelsemine alleviated anxiety-like behaviors in the CUMS-induced mouse model. Gelsemine exerted its anxiolytic effects by modulating the NLRP3 and CREB/BDNF pathways.

Background Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth ( G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. Objective This study aimed to analyse the toxicity characteristics of gelsenicine. Methods Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. Results In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood–brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. Conclusions Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine -related poisoning and its toxicity mechanisms.

No abstract

No abstract

Background: Gelsemium elegans Benth（G. elegans） is a well-known toxic plant. Alkaloids are main active components of G. elegans. Currently, the metabolism of several alkaloids, such as gelsenicine, koumine, and gelsemine, has been widely studied. However, as one of the most important alkaloids in G. elegans, the metabolism of humantenine has not been studied yet. Methods: In order to elaborate on the in vitro metabolism of humantenine, a comparative analysis of its metabolic profile in human, pig, goat and rat liver microsomes was carried out using high-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) for the first time. Results: Totally, ten metabolites of humantenine were identified in liver microsomes from human (HLMs), pig (PLMs), goat (GLMs) and rat (RLMs) based on the accurate MS/MS spectra. Five metabolic pathways of humantenine, including demethylation, dehydrogenation, oxidation, dehydrogenation and oxidation, and demethylation and oxidation, were proposed in this study. There were qualitative and quantitative species differences in the metabolism of humantenine among the four species. Conclusions: The in vitro metabolism of humantenine in HLMs, PLMs, GLMs and RLMs was studied by a sensitive and specific detection method based on HPLC/QqTOF-MS. The results indicated that there were species-related differences in the metabolism of humantenine. This work might be of great significance for the further research and explanation of species differences in terms of toxicological effects of G. elegans.