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Garcinia gardneriana is popularly used in skin disorders; therefore, this article investigated the effect of G. gardneriana extracts from leaves, bark and seeds and two isolated compounds in ear oedema and leucocytes migration caused by croton oil. The topical application of the extract of G. gardneriana leaves was able to reduce (70 € 3%, and ID 50 0.33 mg ⁄ ear) ear oedema, while the seeds (51 € 5%) and the wood (60 € 12%) extracts were less effective. In a time-course evaluation, the leaf extract (1 mg ⁄ ear) was effective when applied 2 hr before and until 3 hr after the stimulation, presenting a higher effectiveness when applied right after croton oil (83 € 7% inhibition). In addition, the leaf extract was able to diminish the myeloperoxidase (MPO) activity in 64 € 13%, which suggests the inhibition of leucocyte infiltration that was confirmed by histological analysis. Also, both biflavonoids isolated from the leaves of G. gardneriana, fukugetin (or morelloflavone) and 13-naringenin-II 8-eriodictyol (GB-2a), were able to reduce ear oedema, with ID 50 values of 0.18 (0.10-0.28) and 0.22 (0.15-0.31) mg ⁄ ear, respectively, besides the inhibition of MPO activity of 52 € 6% and 64 € 5%, respectively. Using the fluorescent probe 2¢,7¢-dichlorodihydrofluorescein diacetate, the leaf extract, fukugetin and GB-2a topically applied to the ear treated with croton oil reduced 52 € 15%, 63 € 17% and 83 € 4%, respectively, the production of reactive oxygen species of the skin. Thus, these results reveal the anti-inflammatory effect of G. gardneriana leaves for topical usage, and both biflavonoids are responsible for this effect.

The receptors underlying the endothelin-dependent component of lung plasma extravasation and leucocyte infiltration induced by oleic acid were assessed in mice. Oleic acid (1 mg.kg(-1) intravenously), but not endothelin-1 (up to 1 nmol.kg(-1) intravenously), increased accumulation of Evans blue in the lungs (excluding the trachea and main bronchi) from 11.8+/-3.9 to 98.6+/-10.7 microg 1 h after injection. Bosentan, the antagonist of endothelin receptors (ET(A) and ET(B)) or the selective ET(B) receptor antagonists Ro 46-8443 or A-192621 (administered 1 h before oleic acid at doses of 30, 10 and 30 mg x kg(-1) respectively) reduced the effect of oleic acid by 71%, 58% and 79% respectively. However, the selective ET(A) receptor antagonist A-127722.5 (10 mg x kg(-1)) was inactive. Oleic acid (2 mg xkg(-1), intravenously) raised the number of total leucocytes, mononuclear cells and neutrophils in broncho-alveolar lavage fluid 4 h after injection. Bosentan and Ro 46-8443 (at doses of 30 and 10 mg x kg(-1) respectively) inhibited the neutrophil infiltration induced by oleic acid by approx. 80%. None of the antagonists modified control (basal) pulmonary microvascular permeability or total and differential cell counts. Thus, endogenous endothelins, acting via ET(B) receptor-dependent mechanisms, play a major role in oleic acid-induced lung injury in the mouse by promoting infiltration of circulating neutrophils and enhancement of pulmonary microvascular plasma extravasation. These findings suggest that either ET(B) or mixed ET(A)/ET(B) receptor antagonists might be beneficial in the treatment of the adult respiratory distress syndrome.