Effect of abietane diterpenes from Plectranthus grandidentatus on T- and B-lymphocyte proliferation.
Five known abietane diterpenes of the royleanone and coleon type, namely, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4) and coleon U (5), isolated from Plectranthus grandidentatus, were evaluated for their effect on the proliferation of human lymphocytes induced by the mitogen PHA. All except 4, showed a dose-dependent suppressor effect, with 3 yielding the most potent antiproliferative activity, followed by 5. These two compounds, that represent diterpenes of the royleanone and coleon type respectively, were also shown to be potent inhibitors of mouse splenocyte proliferation induced by ConA or LPS mitogens. However, the sensitivity of ConA-stimulated splenocytes to their suppressive effect was higher, suggesting a preferential inhibition of T-lymphocyte proliferation. The antiproliferative activity of 3 seemed to be exerted without affecting the expression of the lymphocyte activation marker CD69. On the contrary, 5 was shown to reduce the expression of CD69 of TCD8(+) and B-cells, suggesting a relationship between its antiproliferative effect and the expression of this early marker of activation on these cell populations. The capacity of 5 to induce apoptosis on ConA-stimulated splenocytes could also be related with its antiproliferative activity.
Cerqueira
F
F
CEQOFFUP, Faculdade de Farmácia Universidade do Porto, Porto, Portugal.
Cordeiro-Da-Silva
A
A
Gaspar-Marques
C
C
Simões
F
F
Pinto
M M M
MM
Nascimento
M S J
MS
D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins / Q000494:pharmacology; D031346:Plectranthus; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000099192:CD69 Antigens
D045784:Abietanes; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004224:Diterpenes; D006131:Growth Inhibitors; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D000099192:CD69 Antigens; C057776:coleon O; C103399:royleanone