A novel effect of lobeline on vascular smooth muscle cell: inhibition of proliferation induced by endothelin-1.

Lobeline has a long history of therapeutic use ranging from an emetic and respiratory stimulant to a tobacco smoking cessation agent. Lobelia chinensis Lour, a traditional Chinese herb whose active ingredient is the alkaloid lobeline, demonstrated to antagonize the bioactive effect of endothelin-1 (ET-1) and prevent the proliferation of vascular smooth muscle cells (VSMCs) in hyperlipidemic rats. The objective of the present study was to determine the effects of lobeline on proliferation of cultured human umbilical VSMCs induced by ET-1. The results showed that the increased cell numbers and enhanced [3H]thymidine incorporation induced by ET-1 were inhibited and the transition of cells from static phase (G0/G1) to DNA synthesis (S) and mitotic phase (G2/M) was held back by lobeline in a concentration-dependent manner. Confocal microscopy demonstrated that lobeline markedly decreased the fluorescent intensity of intracellular Ca2+ concentration ([Ca2+]i) with a significant difference from ET group. Cytotoxicity was determined by Trypan blue exclusion. These results demonstrated a novel biological role of lobeline. Lobeline inhibited the proliferation of human umbilical VSMCs induced by ET-1 in a dose-dependent manner and the anti-proliferative effect was involved in the reduce of increased [Ca2+]i, rather than nonspecific cytotoxicity.