Willow bark extract and aspirin – their potential for gastric injury in mice and other toxicity aspects

Objective

Non-steroidal anti-inflammatory drugs carry a high risk of inducing gastrointestinal ulceration and blood loss. Because pharmacological investigations have shown that willow bark extract standardised to 11–13% salicin (ES, extractum Salicis) is a potent anti-inflammatory substance compared with acetylsalicylic acid (ASA), we examined the gastrointestinal tolerability of SE compared with ASA in mice. Basic toxicity data were determined, and the potential of ES to inhibit blood platelet aggregation.

Materials and methods

An LD₅₀ assay was performed and platelet aggregation was measured ex vivo. Mice were treated with a single dose of 60, 100 or 120 mg/kg of SE or 100, 300 or 600 mg/kg ASA. Five hours later, the animals were killed and their stomachs were examined macroscopically.

Results

ES: at 60 mg/kg, 5/6 preparations presented without any changes, one showed one small single petechia. At 100 mg/kg, 3/6 preparations presented without any changes, and three showed small single petechiae. At 120 mg/kg, 5/6 preparations were without any changes; in one preparation, one small single petechia occurred.

ASA: at 100 mg/kg, 7/7 preparations of the gastric wall presented with petechiae and single ulcerations. At 300 mg/kg, 1/7 preparations of the gastric wall were without any changes. In 6/7, petechiae and single ulcerations were found. At 600 mg/kg, 7/7 preparations of the gastric wall showed multiple petechiae and ulcerations. With the dry extract, an LD₅₀ could not be established in mice, whereas liquid extract has an LD₅₀ of 28 ml/kg. Platelet aggregation is inhibited by SE, but to a lesser extent than ASA, and by different mechanism.

Conclusion

As the dosages used were also studied for their anti-inflammatory activity, where, for example, the highest doses of both groups showed comparable activity and the smaller doses of SE were slightly superior to the lower dose levels of ASA, the difference in the toxicity profile for gastric injury potential is unexpected and a potential advantage of standardised Salix preparations.