Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation

Several triterpenes isolated from Leptadenia hastata latex were tested for their anti-inflammatory activity. Lupeol (1), its acetate (2) and palmitate (3) esters were found to be the main antiinflammatory constituents in the croton oil-induced ear oedema test. Furthermore, lupeol hemisuccinate (4), synthesized from lupeol, exhibited a higher activity than lupeol in the tes t. These results prove that the triterpenes play a pivotal role in the topi cal antiinflammatory effect of this latex. In addition, an in vitro model of human skin keratinocytes (epidermal expla nts) cultured at an air-liquid interface on a de-epidermized human dermis D ED) was used to investigate the effects of lupeol esters on skin repair in vitro. Compared with the control, compounds 2 and 3 improved keratinocyte p roliferation at a concentration of 5 muM in the culture medium; however, th ey remained less active than compounds 1 and 4. In contrast to compound 1, all the lupeol esters (2-4), and particularly compound 4, induced a good di fferentiation of keratinocytes with a well-formed stratum corneum without p arakeratosis, These results substantiate the topical use of Leptadenia hast ata latex in traditional medicine and showed that both antiinflammatory act ivity and the effect on keratinocyte proliferation of compound 1 could be i mproved by its hemisuccinylation; on the contrary, esterification by acetyl ation or palmitoylation decreased these activities. Copyright (C) 2001 John Wiley & Sons, Ltd.