Anti-inflammatory action of an alkaloid, fraction and extract from Alchornea glandulosa in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Alchornea glandulosa (Euphorbiaceae) has traditionally been used in medicine for treating immune-mediated inflammatory diseases.

AIM OF STUDY: This work aimed to evaluate the anti-inflammatory effects of a methanolic extract of leaves from A. glandulosa (MEAG), as well as the ethyl acetate fraction (EAFAG) and isolated compound guanidine alkaloid N-1, N-2, N-3-triisopentenylguanidine (AG-1), in experimental in vivo models of inflammation in mice. We also investigated this extract's phenols, flavonoids and flavonol compounds.

MATERIALS AND METHODS: MEAG (extracted by maceration with methanol), EAFAG (fraction resulting from the partition of the methanolic extract with ethyl acetate) and AG-1 (alkaloid isolated by chromatographic methods) were analysed. MEAG and EAFAG were analysed by HPLC/DAD. The effects of MEAG (30, 100 and 300 mg/kg), EAFAG (30, 100 and 300 mg/kg) and AG-1 (5 and 30 mg/kg) were studied in the following experimental mouse models: paw oedema and myeloperoxidase (MPO) activity, croton-oil-induced ear oedema, leukocyte migration in a pleurisy model induced by carrageenan and zymosan induction of joint inflammation.

RESULTS: MEAG and EAFAG were analysed by LC/DAD, and phenolic acids (gallic acid and caffeic acid) and flavonoids (myricetin-3-O-α-rhamnopyranoside and quercetin) were detected. MEAG, EAFAG and AG-1 were used in the carrageenan-induced paw oedema model and showed maximum inhibitions of 60.10% (MEAG, 2 h, 300 mg/kg) and 66.21% (EAFAG, 2 h, 300 mg/kg). AG-1 at 5 mg/kg showed significant inhibition, ranging from 60.92% to 63.13%, at all evaluated times, and the 30 mg/kg dose showed inhibition of 42.12% (1 h) and 40.36% (2 h). MEAG (37%, 46.1% and 68.11%) and EAFAG (31%, 42.21% and 48.93%), at doses of 30, 100 and 300 mg/kg, respectively, significantly reduced the increase in MPO activity, and AG-1 (5 and 30 mg/kg) showed inhibition of 64.62% and 65.12%, respectively. In the pleurisy model, MEAG (300 mg/kg), EAFAG (300 mg/kg) and AG-1 (30 mg/kg) significantly reduced the migration of total leukocytes with maximal inhibition of 80.90%, 83.17% and 89.39%, respectively. In the croton oil model, pretreatment with MEAG (0.1, 0.3 and 1 mg/ear) increased the diameter of the right ear (30.32%, 48.87% and 53.09%, respectively). Finally, MEAG (100 and 300 mg/kg; 33.11% and 56.03%) and EAFAG (100 and 300 mg/kg; 36.89% and 50.53%) reduced zymosan-induced oedema formation.

CONCLUSIONS: To the best of our knowledge, these results are the first to demonstrate that A. glandulosa exhibits oral and topical anti-inflammatory activity. This study detected alkaloid and phenol/polyphenolic compounds in A. glandulosa, which may help to explain the ethnobotanical use of this plant in traditional medicine in Brazil to treat immune-mediated inflammatory diseases.