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Leishmanicidal and anti-inflammatory activities of Lupeol Acetate isolated from Cnidoscolus tehuacanensis Breckon

Ma del Carmen Juarez-Vazquez+, Georgina A. Siordia-Reyes+, Mariana Z. Perez-Gonzalez, Karina A. Chavez-Rueda, M. Victoria Legorreta-Haquet, Rocio Nieto-Meneses, Lilian Yepez-Mulia, Martha L. Macias- Rubalcava, M. Adelina Jimenez-Arellanes*

Cnidoscolus tehuacanensis is an endemic medicinal species used to treat some inflammatory diseases, and biosynthesizes triterpenes and sterols, being Lupeol Acetate (LuAc) the main compound. It was submitted to biological assay to determine the anti-inflammatory and leishmanicidal potential.

Anti-inflammatory effect was determined on acute (12-O-tetradecanoylphorbol-13-acetate -TPA- and Carragenan models) and chronic inflammatory models (induce with Complet Freud´s Adjuvant -CFA-) using Indomethacin and Phenylbutazone (PBZ) as reference drugs. In vitro leishmanicidal activity was determined on Leishmania mexicana promastigotes and amastigotes, Miltefosine and amphotericin B were used as reference drugs.

In TPA assay, LuAc showed an ED₅₀=1.79 mg/ear (Ind, ED₅₀=0.91 mg/ear) and on Carragenan model, the antiinflammatory effect was not dose-dependent, in this case LuAc at 100, 150 and 250 mg/kg showed 43.31, 40.22 and 51.25% of inhibition, respectively at 5 h. On CFA chronic inflammatory model, LuAc and PBZ groups showed similar anti-inflammatory effect and similar Body Weight (BW) gain although this value was less respect to healthy and CFA groups. Also, inhibited the COX-2 activity being this effect slightly better that PBZ, and the joints and soft tissue from LuAc and PBZ groups did not show any alteration with respect to CFA group. In soft tissue, CFA group showed a significant increase size and leukocyte infiltrate as a result of the chronic inflammatory process; it group also showed sinusoidal hyperplasia in the joint. In liver histological analysis, the healthy and LuAc groups showed no alteration, and the CFA group showed a slight microabscess and scarce hematopoiesis, while the PBZ group presented scarce steatosis. The fraction (rich in LuAc) and LuAc pure were less active that extract against L. mexicana promastigotes.

C. tehuacanesis is a potential source of LuAc. This natural compound showed a good anti-inflammatory activity (similar effect to PBZ) and did not cause liver damage.