College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, Hunan, China.
College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, Hunan, China; Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha, 410128, Hunan, China.
Biomed Pharmacother. 2021 May;137:111284. doi: 10.1016/j.biopha.2021.111284. Epub 2021 Feb 6.
Gelsemium elegans (G. elegans) is a flowering plant of the Loganiaceae family, which had been used in traditional Chinese herb medicine for many years for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, anxiety and cancer. Acute toxicity of the plant severely limits the application and development of G. elegans; however, long-term toxicity of exposure to G. elegans has not been illuminated.
This study is a comprehensive observation of the effects of long-term exposure (21 days at 70 mg/kg) to G. elegans in rats.
The histopathological examination showed only a mild glial cell proliferation in the brain, and no lesions were observed in other organs. No abnormal changes in the biochemical parameters were observed that would have significant effects. The identification and analysis of absorbed natural ingredients showed that the active ingredients of the G. elegans could distribute to various tissues, and six compounds were identified in the brain, suggesting that they could cross the blood-brain barrier. Based on the intestinal content metabolomics, the tryptophan (Trp) biosynthesis, bile acid synthesis and bile secretion pathways have attracted our attention. Plasma metabolomic results showed that uric acid (UA) was significantly increased. The results of the brain metabolomic tests showed that the level of pyridoxal (PL) was decreased; considering the expression levels of the related enzymes, it was hypothesized that the level of pyridoxal 5'-phosphate (PLP) was decreased. PLP was important for the regulation of the neuronal γ-aminobutyric acid (GABA)/glutamate (Glu) interconversion and therefore neuronal excitability. The data of the study suggested that toxic reaction caused by G. elegans was due to a disruption of the balance of the neurotransmitter GABA/Glu transformation.
Overall, G. elegans did not cause significant toxic reaction in the rats after long-term exposure. The results were significant for the future clinical applications of G. elegans and suggested that G. elegans could be potentially developed as a drug. The study provided a scientific basis for investigation of the mechanisms of toxicity and detoxification.
钩吻（Gelsemium elegans）是马钱科钩吻属木质藤本植物，多年来一直被用于传统中药治疗类风湿性疼痛、神经痛、痉挛、皮肤溃疡、焦虑和癌症。该植物的急性毒性严重限制了钩吻的应用和发展；然而，长期接触钩吻的长期毒性尚未阐明。
本研究是对大鼠长期暴露（70mg/kg，21 天）钩吻的综合观察。
组织病理学检查仅显示大脑中轻度神经胶质细胞增生，其他器官未见病变。未观察到生化参数有显著影响的异常变化。吸收天然成分的鉴定和分析表明，钩吻的活性成分可以分布到各种组织中，在大脑中鉴定出六种化合物，表明它们可以穿过血脑屏障。基于肠道内容物代谢组学，色氨酸（Trp）生物合成、胆汁酸合成和胆汁分泌途径引起了我们的注意。血浆代谢组学结果显示尿酸（UA）显著增加。大脑代谢组学测试结果表明吡哆醛（PL）水平降低；考虑到相关酶的表达水平，推测吡哆醛 5'-磷酸（PLP）水平降低。PLP 对神经元γ-氨基丁酸（GABA）/谷氨酸（Glu）转化的调节很重要，因此对神经元兴奋性很重要。研究数据表明，钩吻引起的毒性反应是由于神经递质 GABA/Glu 转化的平衡被破坏。
总的来说，长期暴露后，钩吻在大鼠体内未引起明显的毒性反应。这些结果对钩吻未来的临床应用具有重要意义，并表明钩吻可能具有作为药物的潜力。该研究为毒性和解毒机制的研究提供了科学依据。
