Advanced Healthcare Materials
·
2024
·
IF 10
Meng-Meng Chen,Han-Wen Tian,Yuan-Qiu Cheng,Yu-Xin Yue,Yu-Chen Pan,Dong-Sheng Guo
Snakebite is a medical emergency that often leads to high mortality and morbidity in tropical and subtropical regions. The diversity in venom composition between various types of snakes necessitates the use of different specific antivenom treatments, which presents clinical and financial challenges in the management of snakebites. Therefore, developing a broad-spectrum antidote to neutralize complex and diverse snake venoms has assumed critical importance. Herein, a broad-spectrum antidote is developed through molecular recognition and coassembly to neutralize four kinds of snake venom toxins, those are three-finger toxin (3FTx), snake venom metalloproteinase (SVMP), phospholipase A 2 (PLA 2 ), and snake venom serine protease (SVSP), which have high abundance and toxicity. The coassembly of sulfonate-modified amphiphilic calixarene (SCA) and amphiphilic cyclodextrin (CD) is employed to neutralize the toxicity of 3FTx, 1,2-dodecanedithiol (DDT) and thioetheramide phosphorylcholine (TEAPC) are introduced through coassembly to neutralize toxicity of SVMP and PLA 2 , respectively, and the nafamostat (NT), which can be loaded through the host-guest complexation, is employed to neutralize toxicity of SVSP. The broad-spectrum antidote, NT@SCA/CD/DDT/TEAPC, effectively neutralizes key toxins from the most medically important cobra and vipers, significantly improving survival rates of poisoned mice. This study conceptually validated the feasibility of broad-spectrum detoxification and also offers a conveniently integrated supramolecular strategy.
研究领域:
医学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
·
药理学
·
神经科学
·
植物学
·
急诊医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Meng Cheng,Caihua Ye,Chunxiao Tian,Dongju Zhao,Haonan Li,Zuhao Sun,Yuyang Miao,Qiang Zhang,Junping Wang,Yan Dou
Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain, leading to neurodegeneration in Alzheimer's disease (AD). Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses, but is very challenging. Herein, an engineered macrophage-biomimetic versatile nanoantidote ( [email protected] ) is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression. Coating macrophage membranes can not only endow [email protected] with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain, but also efficiently reduce neurotoxin levels to prevent them from activating microglia. The loaded oxytocin (OT) can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4 (TLR4) on microglia, inhibiting TLR4-mediated pro-inflammatory signalling cascade. Benefiting from this two-pronged immunosuppressive strategy, [email protected] exhibits outstanding therapeutic effects on ameliorating cognitive deficits, inhibiting neuronal apoptosis, and enhancing synaptic plasticity in AD mice, accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging. This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.
研究领域:
神经科学
·
药理学
·
纳米技术
·
免疫学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）