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 ...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.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos.2024B1515040014,2022B1515130007,2023B1515040015,and 2023A1515030012,China)the National Natural Science Foundation of China(Nos.82373750,82293681(82293680),82204236,and 82371175)+1 种基金the Science and Technology Key Project of Guangdong Province(Nos.2020B1111110004 and 2023A0505050121,China)the Science and Technology Project in Guangzhou(Nos.2024B03J1286 and 202102070001,China).
文摘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.
