Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Niping Li,Yaorong Yang,Shengyuan Zhang,Bin Jiang,Wei Zhang,Haibo Wang,Lixin Chen,Liwei Wang,Yiyi Li,Lei Shi,Wencai Ye,Lei Wang
Gelsemium elegans ( G. elegans ) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans , resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure–toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine ( 1 ), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine ( 1 ) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA A receptor antagonists successively reversed action potential firing in gelsenicine ( 1 )-treated VRG neurons. Importantly, the GABA A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.
研究领域:
毒理学
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药理学
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神经科学
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植物学
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急诊医学
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DOI
PubMed
高影响因子
FORENSIC SCIENCE INTERNATIONAL
·
2021
·
IF 2.395
Dong Qu,Dong-Fang Qiao,Xun-Cai Chen,Chun-Qiong Feng,Qi-Zhi Luo,Xiao-Hui Tan
We present a case of fatal poisoning from accidental ingestion of Gelsemium elegans ( G. elegans ), a rarely toxic plant. A 41-year-old man was found dead, at his home, 6 h after drinking homemade herbal liqueur during lunch. Autopsy and routine toxicological analyses identified neither significant pathological findings nor routine poisons. However, a local botanist revealed that the homemade herbal liqueur contained G. elegans , a poisonous plant specific to Asia. To ascertain whether the decedent had ingested G. elegans , we performed liquid chromatography-mass spectrometry (LC-MS) and found two alkaloids (gelsemine and koumine) in his blood, gastric contents, as well as the suspected herbal liqueur. The cause of death was therefore confirmed to be G. elegans poisoning. Case reports of fatal poisoning due to ingestion of G. elegans are quite rare in English. Therefore, the present case broadens the scope on the possibility of death due to ingestion of G. elegans for forensic pathologists and toxicologists.
研究领域:
法医病理学
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毒理学
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植物学
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法医学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2014
·Vol. 71
·期 2
·535-541
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IF 2.38
Lin Lin,Zheng Jing,Zhu Weiping,Jia Ning
Cisplatin-induced generation of reactive oxygen species leads to acute nephrotoxicity limiting its use in the treatment of various cancers. Gelsemine, an alkaloid isolated from Gelsemium elegans , is known to possess anti-inflammatory and anti-cancer activities. This study was aimed to investigate as to whether gelsemine can serve as a protective agent against cisplatin-induced nephrotoxicity. Male Wistar rats were divided into 6 groups, each with 6 rats. Group 1 served as control and received the vehicles (peanut oil for 14 days and 0.9 % saline on day 14 for gelsemine and cisplatin respectively). Group 2 received a single intraperitoneal injection of cisplatin on day 14. Group 3 and 4 were pretreated with two different doses of gelsemine in addition to cisplatin, and group 5 and 6 received only gelsemine. The effects of gelsemine on cisplatin-induced nephrotoxicity were examined by measuring anti-oxidant enzymes activities, lipid peroxidation, and DNA damage in the kidneys, a well-established model of oxidative damage. Pretreatment of rats with gelsemine caused a significant attenuation of cisplatin-induced DNA and oxidative damages. The blockade of lipid peroxidation and xanthine oxidase activity was accompanied by increased production and/or activity of anti-oxidants, both enzymatic (catalase, glutathione peroxidase, glutathione reductase, and glutathione- S -transferase) and non-enzymatic (GSH). The biomarkers of kidney malfunctioning, creatinine, and blood urea nitrogen were ameliorated. The results of the present study suggest that gelsemine effectively suppressed cisplatin-induced renal injury by improving redox status.
研究领域:
药理学
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毒理学
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肿瘤学
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肾脏生理学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2020
·Vol. 21
·期 8
·1-11
·
IF 2.401
Su Yanping,Lu Wenxiang,Fu Xiaoling,Xu Ying,Ye Lixiang,Yang Jian,Huang Huihui,Yu Changxi
The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93–3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration ( C max ) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration ( T max ) and the half-life ( t 1/2 ) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC 0–72 h ) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine.
研究领域:
药学
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药理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
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