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当归属提取物对绝经后条件下 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的多巴胺能神经元毒性的保护作用。

Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.

机构信息

Department of Oriental Gynecology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.

出版信息

J Ethnopharmacol. 2012 Feb 15;139(3):883-8. doi: 10.1016/j.jep.2011.12.015. Epub 2011 Dec 13.

DOI:10.1016/j.jep.2011.12.015
PMID:22178176
Abstract

UNLABELLED

Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.

ETHNOPHARMACOLOGICAL RELEVANCE

Dangguijakyak-san (DJS), a famous traditional herbal formula, has long been used to treat gynecological disorders, including postmenopausal symptoms. This study evaluated the effects and mechanism of DJS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a postmenopausal mouse model induced by ovariectomy.

MATERIALS AND METHODS

Three weeks after ovariectomy, C57bl/6 female mice were divided randomly into (1) control, (2) MPTP (30 mg/kg/day, i.p., 5 days), (3) MPTP+estrogen (50 μg/kg/day, i.p., 5 days), and (4) MPTP+DJS (50 mg/kg/day, p.o., 5 days) groups. We investigated the behavioral recovery and dopamine neuron protection of DJS using the pole test and tyrosine hydroxylase (TH) immunohistochemistry. We also explored the mechanism by assessing the protein expression of Bax, Bcl-2, cytochrome c, and cleaved caspase-3.

RESULTS

DJS treatment restored the movement behavior impaired by MPTP, showing a similar or better effect than estrogen. DJS protected TH-immunoreactive cells and fibers in the nigrostriatal region from MPTP toxicity. In addition, DJS inhibited the Bcl-2 decrease and Bax increase in mitochondria, cytochrome c release to the cytosol, and caspase-3 activation induced by MPTP.

CONCLUSIONS

DJS showed behavior recovery and dopamine neuron protection against MPTP-induced toxicity via anti-apoptotic activities in ovariectomized female mice. These results suggest that DJS treatment is effective for postmenopausal neurodegenerative diseases.

摘要

未加标签

当归芍药散在绝经后条件下保护多巴胺神经元免受 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的神经毒性。

民族药理学相关性

当归芍药散(DJS)是一种著名的传统草药配方,长期以来一直用于治疗妇科疾病,包括绝经后症状。本研究评估了 DJS 对卵巢切除术后绝经小鼠模型中 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的神经毒性的作用和机制。

材料和方法

卵巢切除 3 周后,C57bl/6 雌性小鼠随机分为(1)对照组,(2)MPTP(30 mg/kg/天,腹腔注射,5 天),(3)MPTP+雌激素(50 μg/kg/天,腹腔注射,5 天)和(4)MPTP+DJS(50 mg/kg/天,口服,5 天)组。我们使用杆试验和酪氨酸羟化酶(TH)免疫组织化学法研究 DJS 对行为恢复和多巴胺神经元的保护作用。我们还通过评估 Bax、Bcl-2、细胞色素 c 和切割的 caspase-3 的蛋白表达来探讨机制。

结果

DJS 治疗恢复了由 MPTP 引起的运动行为障碍,效果与雌激素相似或更好。DJS 保护黑质纹状体区域中的 TH 免疫反应性细胞和纤维免受 MPTP 毒性的影响。此外,DJS 抑制了 MPTP 诱导的线粒体中 Bcl-2 减少和 Bax 增加、细胞色素 c 向细胞质释放以及 caspase-3 激活。

结论

DJS 通过抗凋亡活性在卵巢切除雌性小鼠中显示出对 MPTP 诱导的毒性的行为恢复和多巴胺神经元保护作用。这些结果表明 DJS 治疗对绝经后神经退行性疾病有效。

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