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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产品关联
DOI
PubMed
高影响因子
NEUROENDOCRINOLOGY
·
2024
·
IF 3.2
Zhang Jiaxian,Lai Wanlin,Tang Yusha,Gao Jing,Zhou Xiangyang,Chen Lei
Introduction:
In women of childbearing age with epilepsy, 40% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy. Methods:
A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. Susceptibility was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35. Results:
This study revealed that letrozole induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with anti-epileptic status in PCOS rats. Conclusion:
This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS
研究领域:
神经科学
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内分泌学
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癫痫研究
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生殖医学
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DOI
PubMed
高影响因子
Molecular Brain
·
2019
·Vol. 12
·期 1
·1-12
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IF 4.051
Wang Xin-shang,Guan Shao-yu,Liu An,Yue Jiao,Hu Li-ning,Zhang Kun,Yang Liu-kun,Lu Liang,Tian Zhen,Zhao Ming-gao,Liu Shui-bing
Chronic pain is commonly accompanied with anxiety disorder, which complicates treatment. In this study, we investigated the analgesic and anxiolytic effects of Formononetin (FMNT), an active component of traditional Chinese medicine red clover ( Trifolium pratense L.) that is capable of protecting neurons from N-methyl-D-aspartate (NMDA)-evoked excitotoxic injury, on mice suffering from complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain. The results show that FMNT administration significantly reduces anxiety-like behavior but does not affect the nociceptive threshold in CFA-injected mice. The treatment reverses the upregulation of NMDA, GluA1, and GABA A receptors, as well as PSD95 and CREB in the basolateral amygdala (BLA). The effects of FMNT on NMDA receptors and CREB binding protein (CBP) were further confirmed by the potential structure combination between these compounds, which was analyzed by in silico docking technology. FMNT also inhibits the activation of the NF-κB signaling pathway and microglia in the BLA of mice suffering from chronic inflammatory pain. Therefore, the anxiolytic effects of FMNT are partially due to the attenuation of inflammation and neuronal hyperexcitability through the inhibition of NMDA receptor and CBP in the BLA.
研究领域:
药理学
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神经科学
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疼痛研究
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传统中药
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DOI
PubMed
高影响因子
Neural Regeneration Research
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2022
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IF 6.058
Ting-Ting Cao,Huan Chen,Mao Pang,Si-Si Xu,Hui-Quan Wen,Bin Liu,Li-Min Rong,Mang-Mang Li
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 10 6 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 10 6 cells/kg), medium (1 × 10 6 cells/kg) and high (4 × 10 6 cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABA A ) receptor expression by the effective doses indicates that GABA A receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 10 6 hUC-MSCs/kg is an alternative approach for treating subacute SCI.
研究领域:
干细胞治疗
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神经科学
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脊髓损伤
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细胞生物学
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医学影像
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产品关联
DOI
PubMed
高影响因子
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