Astragaloside IV protects rat gastric mucosa against aspirin-induced damage.
Aspirin (Asp) is commonly used as an anti-inflammatory drug, but the long-term usage of Asp can lead to severe gastrointestinal damage. Thus the co-administering of Asp with another drug that can suppress its side effect while having no impact on its anti-inflammatory activity would be ideal. Astragaloside IV (AST-IV) is a natural anti-inflammatory compound that has been shown to protect rat gastric mucosa from anhydrous ethanol-inflicted damage. In this study, we investigated whether AST-IV could protect rat gastric mucosa against Asp-induced gastric mucosal damage. Wistar rats administered 150mg/kg Asp showed significant damage to the gastric mucosa, as revealed by gastric damage score and histological evaluation. However, this was largely abolished by co-administering Asp and 25mg/kg or 50mg/kg AST-IV. The protective mechanism of AST-IV involved the suppression of Asp-induced inhibition of cycloxygenase-1 (COX-1) expression, prostaglandin E2(PGE2) production, superoxide dismutase (SOD) activity and nitric oxide (NO) production. AST-IV blocked Asp-induced inhibition of SOD activity through preventing Asp from inhibiting the expression of SOD-1, both at the mRNA and protein levels. AST-IV did not appear to interfere with the anti-inflammatory activity of Asp since COX-2 level in model gastritis rats treated with Asp plus AST-IV was equally suppressed as in model gastritis rats treated with Asp alone. The results clearly showed that AST-IV could neutralize the toxicity of Asp while having no impact on its anti-inflammatory activity. AST-IV could therefore be considered as a potential drug for relieving the side effect associated with the long-term usage of Asp.
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Dan-Dan
DD
Fan
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Shan
S
Lin
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Yan-Ping
YP
Song
School of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Ze-Yu
ZY
Wang
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Bo
B
Liu
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Sai-Nan
SN
Gao
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Yu-Hua
YH
Fan
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
Shan
S
Zhu
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China. Electronic address: lisen_116@163.com.
Sen
S
Li
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China. Electronic address: 120532190@qq.com.
Lei
L
Jiang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D020011:Protective Agents; D012503:Saponins; D014315:Triterpenes; D009569:Nitric Oxide; C052064:astragaloside A; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D015232:Dinoprostone; D001241:Aspirin
Aspirin; Astragaloside IV; Gastric mucosal; Protective effect