The mixture of Salvia miltiorrhiza-Carthamus tinctorius (Danhong injection) alleviates low-dose aspirin induced gastric mucosal damage in rats

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• 作者：Jian-ping Li^a ; ^b ; ¹ ; Jian-ming Guo^a ; ^b ; ¹ ; Yong-qing Hua^a ; ^b ; Kevin Yue Zhu^a ; ^b ; Yu-ping Tang^a ; ^b ; Bu-chang Zhao^c ; Li-fu Jia^c ; Jing Zhao^c ; Zhi-shu Tang^d ; Jin-ao Duan^a ; ^b ; ^{dja@njucm.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; ^{dja@njutcm.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Danhong injection ; Aspirin ; Drug interaction ; Cyclooxygenase ; Drug combination ; Gastric mucosal damage
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：23
• 期：6
• 页码：662-671
• 全文大小：3691 K

文摘

Danhong injection (DHI) is quite often used in combination with low-dose aspirin (ASA, 75–325 mg daily) in clinic, particularly for the treatment of cardiovascular diseases. Exploring their interaction profile is of great clinical importance.

Purpose

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 2 h 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 (71.9 µM) 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 1.83–1.94 µg/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.