Wound healing activity of the hydroalcoholic extract and the main metabolites of Amphipterygium adstringens (cuachalalate) in a rat excision model

Ethnopharmacological relevance: The bark of Amphipterygium adstringens Schiede ex Schltdl (Anacardiaceae), commonly known as 'cuachalalate' has been used in Mexican traditional medicine for the treatment of skin and oral lesions, gastric ulcers, and other conditions. The use as wound healing of the bark of this plant has been known since before the Spanish conquest of Mexico. Its uses are mentioned in the first writings of the Spanish in the 16th century. It is important to highlight that its use for wound healing treatment has no scientific previous reports. Aim of the study: The objectives of this study were to determine the wound healing effect of the hydroalcoholic extract of the stem bark of Amphipterygium adstringens and its main metabolites, using a model of excision in the back of Wistar rats. To evaluate its antimicrobial effect against common bacteria that living on the skin of wounds and to evaluate its effect on angiogenesis. Materials and methods: The hydroalcoholic extract of cuachalalate (HAE, 10 mg/wound/day), the 3 alpha-hydroxymasticadienoic acid (3 MA, 300 mu g/wound/day), the masticadienoic acid (MA, 300 mu g/wound/day), and a mixture of anacardic acids (ANA, 300 mu g per wound) were tested in a murine excision model topically for 15 days, to evaluate their wound-healing effect. The results were reported in a wound closure percentage (n = 30 animals per treatment curve), using pirfenidone (PIR, 8% in vehicle) as a reference drug. In addition, histologic analysis was performed to evaluate the structure and quality of the scar. The effect on angiogenesis was assessed using the chick embryo chorioallantoic membrane (CAM) model (n = 6 eggs per treatment). The concentration evaluated for each treatment was 300 mu g, using as proangiogenic reference drug the histamine (HIS, 5.6 mu g) and as antiangiogenic drugs pirfenidone (9 mu g) and acetylsalicylic acid (ASA, 9 mu g). The antimicrobial test was performed against S. mutans, S. aureus, P. aeruginosa y E. coli using a minimum inhibitory concentration (MIC) assay. Results: The 3 alpha-hydroxymasticadienoic (3 MA) acid and the anacardic acids (ANA) improve the wound closure by approximates 30% (similar to pirfenidone) in comparison with the control-treated with the vehicle in the proliferative phase. On the other hand, the hydroalcoholic extract of cuachalalate (HAE) did not show an effect on the wound healing process. The histologic analysis demonstrated that the three main metabolites showed an improvement in the scar structure. According to the CAM results, it is probable that the main action mechanism of the 3 alpha-hydroxymasticadienoic acid and the anacardic acids is related to their proangiogenic effect. In addition, ANA showed a modest antimicrobial effect. Conclusions: The 3 alpha-hydroxymasticadienoic acid and anacardic acids showed a better tissue structure and reduced the time closure of the wound. In addition, the anacardic acids showed antimicrobial effects and both metabolites promote angiogenesis, suggesting that these effects may be related to their action mechanism. These metabolites of cuachalalate could be a good alternative for wound healing treatment.