Sun Linjia, Chen Yu, Hou Chenzhi, Sun Xiaoyang, Wang Zhipeng, Li Shujuan, Lv Mingming, Chen Xiaohui
School of Pharmacy, Shenyang Pharmaceutical University 103 Wenhua Road in Shenhe District Shenyang China 110016
Department of Pharmaceutical Analysis, China Pharmaceutical University Nanjing China.
RSC Adv. 2018 Aug 16;8(51):29210-29219. doi: 10.1039/c8ra05384g. eCollection 2018 Aug 14.
, a classical traditional Chinese medicine, has been widely used for its anti-tumor, analgesic and anti-inflammatory angiogenesis effects. However, taking an overdose of might result in extreme neurotoxicity. Strychnos alkaloids are the main toxic constituents of Total glycosides from paeonies are considered to have neuroprotective effects. In this study, twelve potential endogenous biomarkers in rat serum and brain were monitored to investigate the protective effect of total glycosides from the paeony against strychnos alkaloids-induced neurotoxicity. A sensitive liquid chromatography-tandem mass spectrometry method was developed and validated to monitor eight neurotransmitters including glutamate, γ-aminobutyric acid, acetylcholine serotonin, dopamine, norepinephrine, tryptophan and tyrosine. An enzyme-linked immunosorbent assay method was selected for determination of four neuroendocrine hormones including thyrotrophin-releasing hormone, corticotrophin-releasing hormone, antidiuretic hormone and prolactin. Results showed that continuous administration of strychnos alkaloids for 15 days caused significant changed levels of the biomarkers (especially the four neuroendocrine hormones). Meanwhile, total glycosides from paeony pretreated rats (administrated with total glycosides from the paeony for 15 days before exposure to strychnos alkaloids) showed recovered levels of these biomarkers. The results suggested that the neurotransmitters and neuroendocrine hormones in serum and brain might play potential roles as biomarkers. This study provides the possibility of alleviating the -induced neurotoxicity in clinic by pre-protection with total glycosides from paeonies.
作为一种经典的传统中药,因其抗肿瘤、镇痛和抗炎血管生成作用而被广泛使用。然而,过量服用可能会导致极端的神经毒性。马钱子生物碱是其主要毒性成分。芍药总苷被认为具有神经保护作用。在本研究中,监测了大鼠血清和大脑中的12种潜在内源性生物标志物,以研究芍药总苷对马钱子生物碱诱导的神经毒性的保护作用。开发并验证了一种灵敏的液相色谱-串联质谱法,用于监测包括谷氨酸、γ-氨基丁酸、乙酰胆碱、血清素、多巴胺、去甲肾上腺素、色氨酸和酪氨酸在内的8种神经递质。选择酶联免疫吸附测定法测定包括促甲状腺激素释放激素、促肾上腺皮质激素释放激素、抗利尿激素和催乳素在内的4种神经内分泌激素。结果表明,连续15天给予马钱子生物碱会导致生物标志物水平发生显著变化(尤其是4种神经内分泌激素)。同时,芍药总苷预处理的大鼠(在暴露于马钱子生物碱之前给予芍药总苷15天)这些生物标志物的水平有所恢复。结果表明,血清和大脑中的神经递质和神经内分泌激素可能作为生物标志物发挥潜在作用。本研究为临床通过芍药总苷预保护减轻其诱导的神经毒性提供了可能性。