title: The mixture of Salvia miltiorrhiza-Carthamus tinctorius (Danhong injection) alleviates low-dose aspirin induced gastric mucosal damage in rats.
abstract: BACKGROUND
  Danhong injection (DHI) is quite often used in combination with low-dose aspirin (ASA, 75-325mg daily) in clinic, particularly for the treatment of cardiovascular diseases. Exploring their interaction profile is of great clinical importance.
  
  
  OBJECTIVE
  The current study aims to explore the interaction between DHI and low-dose ASA in rats.
  
  
  METHODS
  Sixty four rats were randomly divided into eight groups. Stomach and other four vital organs were collected for histological evaluation. Organs which exhibited histological changes were selected for a further study to evaluate the damage score and mode of action. We tested the protective effect of DHI on gastric mucosal damage in different regimes of administration. COX activity, gastric mucus secretion, pepsin activity, antioxidant activity and ROS level were assayed to reflect the protective effect of DHI on gastric mucosal damage induced by ASA.
  
  
  RESULTS
  Stomach was the target organ of interaction when DHI and ASA were used in combination. DHI alleviated gastric mucosal damage by 55.8% when DHI was injected before ASA (Group E) and by 53.5% when DHI was injected 2h after ASA administration (Group F). Additionally, if DHI treatment was appended to the long-term administration of ASA, DHI still decreased the gastric mucosal damage score in 52.0% from 2.50 to 1.20. DHI improved gastric mucus secretion, as well as decreased pepsin activity to maintain the integrity of gastric mucosal barrier (P<0.05). Furthermore, DHI recovered antioxidant activity which was impaired by ASA. In details, DHI decreased gastric mucosal ROS level, increased CAT, GSH-Px and SOD activity, and reduced MDA concentration (P<0.05). When ASA (71.9µM) was used in combination with DHI (23-fold dilution, presented in terms of concentrations of DSS, PA, SaD RA, SaB and SaA were 6.45-6.92, 1.10-1.14, 1.09-1.10, 0.86-0.90, 16.76-19.38 and 1.83-1.94µg/ml, respectively) in vitro, the inhibition rate of ASA increased from 38.6% (ASA alone) to 62.8% (ASA-DHI) on COX-1 and from 28.9% (ASA alone) to 38.8% (ASA-DHI) on COX-2 (P<0.05). DHI strengthened the inhibition activity of ASA on both COX-1 and COX-2, which showed that DHI alleviated ASA induced gastric mucosal damage but not antagonized anti-COX effect of ASA.
  
  
  CONCLUSIONS
  Gastric protective benefits were clearly produced when DHI and ASA were used in combination, which provided rational guidance for clinical combined application of DHI and ASA.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Hua
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Kevin Yue
authors.initials: KY
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: Buchang Pharma, Xi'an 710000, China.
authors.forename: Bu-Chang
authors.initials: BC
authors.lastname: Zhao
authors.affiliation: Buchang Pharma, Xi'an 710000, China.
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Jia
authors.affiliation: Buchang Pharma, Xi'an 710000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Shanxi University of Chinese Medicine, Xianyang 712000, China.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Tang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njucm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000818:Animals; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D031187:Carthamus tinctorius / Q000737:chemistry; D002681:China; D004338:Drug Combinations; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D027561:Salvia miltiorrhiza / Q000737:chemistry
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C540581:danhong; D001241:Aspirin
keywords: Aspirin; Cyclooxygenase; Danhong injection; Drug combination; Drug interaction; Gastric mucosal damage