Dual effects of lipophilic extract of Salvia miltiorrhiza (Danshen) on catecholamine secretion in cultured bovine adrenal medullary cells
Dual effects of lipophilic extract of Salvia miltiorrhiza (Danshen) on catecholamine secretion in cultured bovine adrenal medullary cells
复制标题
丹参亲脂提取物对培养牛肾上腺髓质细胞儿茶酚胺分泌的双重作用
DOI：
10.1016/j.jep.2009.06.010
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发表时间：
2009-08-17
影响因子：
5.4
通讯作者：
Gao, Xiumei
中科院分区：
文献类型：
--
作者：
Mao, Haoping;Zhang, Han;Gao, Xiumei
民族药理学相关性：丹参（Salvia miltiorrhiza，Danshen）是一种传统中药，在临床上被广泛应用于心血管疾病的治疗。本研究的目的：本研究旨在阐明丹参脂溶性提取物（lipopolytic extract：of Salvia miltiorrhiza，LESM）对我国广泛应用于心血管疾病治疗的中药-采用HPLC-ECD法检测LESM对CA分泌的影响。结果：LEMS以细胞外Ca ~（2+）依赖的方式直接刺激基础CA分泌。同时联合应用nAChR抑制剂六甲铵（Hex）对该刺激无明显影响。LESM也直接升高[Ca ~（2+）]。此外，使用电压依赖性Ca ~（2+）通道的选择性阻断剂，如尼群地平（L型）、ω-agatoxin-IVA（P型）和ω-conotoxin-GVIA（N型），发现尼群地平抑制LESM诱导的[Ca ~（2+）]（i）升高，但不抑制ω-agatoxin-IVA或ω-conotoxin-GVIA。但与单独给予乙酰胆碱（ACh）相比，LESM与ACh合用可抑制CA分泌、Na-22（+）内流和[Ca ~（2+）]（i）的增加，且呈浓度依赖性。此外，LESM还抑制由藜芦碱（Ver）和56 mM K+诱导的CA分泌，浓度与[Ca 2 +]（i）升高相似。结论：LESM对牛肾上腺髓质细胞CA分泌具有双重作用。LESM对nAChR、电压依赖性Na ~+和Ca ~（2+）通道具有拮抗作用，而单独使用时则是L型Ca ~（2+）通道的激动剂。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
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 Na-22(+) 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+]. In addition, using selective blockers; of voltage-dependent Ca2+ channels, such as nitrendipine (for L-type), omega-agatoxin-IVA (for P-type) and omega-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, Na-22(+) 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.