Song Xiaodan, Zhu Wenliang, An Ran, Li Yamei, Du Zhimin
Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China.
College of Pharmacy, Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China.
BMC Complement Altern Med. 2015 May 14;15:149. doi: 10.1186/s12906-015-0668-6.
Accumulating evidence has shown that chronic cerebral ischemia (CCI) is one of the major causes of vascular dementia (VD) characterized by dysregulated cholesterol homeostasis and lipoprotein disturbances. Positive value of lipid-lowering agents has been widely evaluated for the treatment of VD. In the present study, we investigated whether Daming capsule (DMC) protected against CCI-induced VD and its possible mechanisms of action. DMC is a multi-herbal formula composed of Rheum palmatum L., Cassia obtusifolia L., Salvia miltiorrhiza, and Panax ginseng C.A., which has been used to treat hyperlipidemia for years in China.
A network pharmacology method was established to reveal whether DMC contained any chemical constituent targeting CCI-related proteins. Furthermore, the potential anti-CCI effects of DMC (100 mg/kg or 200 mg/kg) administered for 30 days were investigated in vivo on rats that were subjected to permanent bilateral occlusion of the carotid arteries (2-VO). Spatial learning and memory abilities were evaluated using a Morris water maze (MWM) and morphological changes of cerebral cortex and hippocampus were assessed using hematoxylin and eosin staining. Moreover, the lipid peroxidation levels and antioxidative capabilities were measured using biochemical analysis.
Our network pharmacology analysis revealed the existence of multiple CCI-related chemical-target interactions in DMC, suggesting a potential protective effect. An in vivo experiment verified that 200 mg/kg DMC improved cognitive deficits of 2-VO rats in the MWM test and attenuated pathological alterations in both the cerebral cortex and the hippocampus. Biochemical assays indicated that DMC decreased malondialdehyde levels and CCI-elevated superoxide dismutase activities, but increased the activities of glutathione peroxidase and catalase.
Our findings suggested that DMC protected against cognitive dysfunction and nerve injuries caused by CCI, which is most likely related to its antioxidant actions.
越来越多的证据表明，慢性脑缺血（CCI）是血管性痴呆（VD）的主要病因之一，其特征是胆固醇稳态失调和脂蛋白紊乱。降脂药物对VD治疗的积极作用已得到广泛评估。在本研究中，我们调查了大明胶囊（DMC）是否对CCI诱导的VD具有保护作用及其可能的作用机制。DMC是一种由大黄、决明子、丹参和人参组成的多草药配方，在中国已用于治疗高脂血症多年。
建立网络药理学方法以揭示DMC是否含有针对CCI相关蛋白的任何化学成分。此外，在体内对接受双侧颈总动脉永久性闭塞（2-VO）的大鼠研究了连续30天给予DMC（100mg/kg或200mg/kg）的潜在抗CCI作用。使用Morris水迷宫（MWM）评估空间学习和记忆能力，并使用苏木精和伊红染色评估大脑皮层和海马体的形态变化。此外，使用生化分析测量脂质过氧化水平和抗氧化能力。
我们的网络药理学分析揭示了DMC中存在多种与CCI相关的化学-靶点相互作用，表明其具有潜在的保护作用。体内实验证实，200mg/kg DMC改善了2-VO大鼠在MWM测试中的认知缺陷，并减轻了大脑皮层和海马体的病理改变。生化分析表明，DMC降低了丙二醛水平，提高了CCI升高的超氧化物歧化酶活性，但增加了谷胱甘肽过氧化物酶和过氧化氢酶的活性。
我们的研究结果表明，DMC对CCI引起的认知功能障碍和神经损伤具有保护作用，这很可能与其抗氧化作用有关。
