title: Protective effect of Daming capsule against chronic cerebral ischemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our findings suggested that DMC protected against cognitive dysfunction and nerve injuries caused by CCI, which is most likely related to its antioxidant actions.
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. danxsong@163.com.|College of Pharmacy, Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. danxsong@163.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Song
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. wenzwl@yeah.net.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. ranan86@163.com.
authors.forename: Ran
authors.initials: R
authors.lastname: An
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. liyamei89@163.com.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. dzm1956@126.com.|Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China. dzm1956@126.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002339:Carotid Arteries; D002366:Cassia; D002374:Catalase / Q000378:metabolism; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005894:Panax; D008517:Phytotherapy; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012250:Rheum; D027561:Salvia miltiorrhiza
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase