Ethnopharmacological relevance: Salvia miltiorrhiza (Danshen) is a well known traditional Chinese herb, which has been used widely in China for the treatment of cardiovascular diseases in clinic.
Aim of this study: The aim of the present study is to clarify the effects of lipophilic extract of Salvia miltiorrhiza (LESM) on catecholamine (CA) secretion, a traditional Chinese medicine used widely for the treatment of cardiovascular diseases in China.
Materials and methods: LESM was evaluated for its effects on CA secretion using HPLC-ECD method. The effects of LESM on 22Na+ influx and intracellular calcium ([Ca2+]i) were also investigated.
Results: Our results showed that LEMS directly stimulated basal CA secretion in an extracellular Ca2+-dependent manner. And the stimulation was not affected by combination of hexamethonium (Hex),an inhibitor of nAChR. LESM also directly elevated [Ca2+]i. In addition, using selective blockers of voltage-dependent Ca2+ channels, such as nitrendipine (for L-type), omega-agatoxin-IVA (for P-type) and -conotoxin-GVIA (for N-type), it was found that nitrendipine suppressed the elevation of [Ca2+]i induced by LESM, but not omega-agatoxin-IVA or omega-conotoxin-GVIA. Compared with acetylcholine (ACh) only, however, combination of LESM with ACh inhibited the raise of CA secretion, 22Na+ influx and [Ca2+]i in a concentration-dependent manner. Furthermore, LESM also inhibited CA secretion induced by veratridine (Ver), and 56 mM K+ at concentrations similar to those for [Ca2+]i rise. One of the lipophilic active compounds, cryptotanshione (Cryp), also had the same effects on CA secretion with LESM.
Conclusions: All these findings suggest that LESM exerts dual effects on CA secretion in cultured bovine adrenal medullary cells. LESM exerts antagonistic effects on nAChR, voltage-dependent Na+ and Ca2+ channels, whereas it is an agonist of L-type Ca2+ channel when it used alone.