Effects of a Chinese herbal preparation on vascular cells in culture: mechanisms of cardiovascular protection

1. The use of traditional Chinese medicinal herbs or their pharmaceutical products for disease prevention and management is becoming increasingly popular in Western countries. Mixtures of various Chinese herbs have been used for the treatment of syndromes clinically overlapping Western cardiovascular syndromes. One modern preparation, known as the 'Cardiotonic Pill' (CP), is a pharmaceutical product derived mainly from a medicinal herb, Salvia miltiorrhiza bunge, and recently widely used in Chinese hospitals for the prevention and management of ischaemic cardiovascular diseases. Although the CP is believed to confer an extensive range of benefits, little is known about the physiological actions of this medicine, particularly at the cellular and molecular levels. Therefore, the aim of the present study was to explore possible cellular mechanisms of the CP on the cardiovascular system. 2. Cultured human vascular endothelial cells (EC) and vascular smooth muscle cells (VSMC) were exposed to the CP at various concentrations for periods ranging from hours to days. Cellular DNA synthesis was determined by a [(3)H]-thymidine incorporation assay, proliferation and death were assessed by investigations of cell numbers and apoptosis, whereas the expression of extracellular adhesion molecules was analysed by flow-cytometry and Western blotting. 3. The CP extract at concentrations of less than 200 microg/mL was not associated with cell damage. At doses beyond the therapeutic range (10-20 microg/mL), the CP appeared to exert a mild inhibitory effect on DNA synthesis and proliferation of EC in serum-enriched cultures. The CP significantly attenuated tumour necrosis factor-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in a dose-dependent manner, with 50 and 100 microg/mL CP producing decreases in the expression of ICAM-1 of 26-32% and 32-44%, respectively, and of VCAM-1 of approximately 23% and 27-42%, respectively. The CP did not affect apoptosis in EC under conditions of serum-deprivation. 4. In VSMC, the CP significantly inhibited platelet-derived growth factor BB-induced DNA synthesis and cell proliferation in a dose-dependent manner. The CP did not affect VSMC expression of adhesion molecules. 5. We conclude that the CP inhibits expression of ICAM-1 and VCAM-1 in EC and proliferation of VSMC in a manner that has potentially beneficial therapeutic effects.