Colombo Giancarlo, Serra Salvatore, Vacca Giovanni, Orrù Alessandro, Maccioni Paola, Morazzoni Paolo, Bombardelli Ezio, Riva Antonella, Gessa Gian Luigi, Carai Mauro A M
C.N.R. Institute of Neuroscience, Cagliari, Italy.
Alcohol Clin Exp Res. 2006 May;30(5):754-62. doi: 10.1111/j.1530-0277.2006.00088.x.
Previous work found that extracts from the roots of Salvia miltiorrhiza, a Chinese medicinal herb, reduced alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to evaluate whether miltirone, one of the possible active constituents of S. miltiorrhiza, might be responsible for the reducing effect of the extracts on alcohol intake.
An initial experiment assessed the effect of 100 mg/kg (intragastric, i.g.) of 4 extracts of S. miltiorrhiza, differing in miltirone content (0, 2, 3, and 7%, respectively), on alcohol intake in alcohol-experienced sP rats exposed to the 2-bottle "alcohol (10%, volume in volume) versus water" choice regimen. Subsequently, the effect of pure miltirone (2.5-10 mg/kg, i.g., i.e., a dose range comparable to its content in the effective doses of the active extracts) on acquisition and maintenance of alcohol-drinking behavior was evaluated in alcohol-naive and alcohol-experienced sP rats exposed to the 2-bottle choice regimen. The effect of miltirone (10 mg/kg, i.g.) on blood alcohol levels was assessed after the i.g. and intraperitoneal (i.p.) administration of alcohol. Finally, the effect of miltirone (30-100 mg/kg, i.g.) on the severity of alcohol withdrawal syndrome was evaluated in Wistar rats made physically dependent on alcohol by the repeated administration of intoxicating doses of alcohol.
The reducing effect of 4 different extracts of S. miltiorrhiza on alcohol intake was positively and significantly correlated with their miltirone content. Pure miltirone reduced alcohol intake in alcohol-experienced rats and delayed acquisition of alcohol-drinking behavior in alcohol-naive rats. Similar to S. miltiorrhiza extracts, miltirone markedly reduced blood alcohol levels when alcohol was administered i.g. but not i.p., suggesting that miltirone hampered alcohol absorption from the gastrointestinal system. Finally, miltirone failed to affect the severity of alcohol withdrawal syndrome in alcohol-dependent rats.
The results of the present study suggest that miltirone is the likely active constituent of S. miltiorrhiza responsible for the reducing effect of its extracts on alcohol intake in different experimental models of excessive alcohol consumption.
先前的研究发现，中药丹参根提取物可降低选择性培育的撒丁岛嗜酒（sP）大鼠的酒精摄入量。本研究旨在评估丹参的一种可能活性成分丹参酮是否是提取物降低酒精摄入量作用的原因。
初步实验评估了100mg/kg（灌胃，i.g.）的4种丹参提取物（丹参酮含量分别为0、2、3和7%）对接触两瓶“酒精（10%，体积比）对水”选择方案的有酒精经验的sP大鼠酒精摄入量的影响。随后，在接触两瓶选择方案的无酒精经验和有酒精经验的sP大鼠中，评估了纯丹参酮（2.5 - 10mg/kg，i.g.，即与有效提取物中其含量相当的剂量范围）对酒精饮用行为习得和维持的影响。在灌胃和腹腔注射（i.p.）酒精后，评估丹参酮（10mg/kg，i.g.）对血液酒精水平的影响。最后，在通过重复给予中毒剂量酒精使身体对酒精产生依赖的Wistar大鼠中，评估丹参酮（30 - 100mg/kg，i.g.）对酒精戒断综合征严重程度的影响。
4种不同丹参提取物对酒精摄入量的降低作用与其丹参酮含量呈正相关且显著相关。纯丹参酮降低了有酒精经验大鼠的酒精摄入量，并延迟了无酒精经验大鼠酒精饮用行为的习得。与丹参提取物相似，当灌胃给予酒精时，丹参酮显著降低血液酒精水平，但腹腔注射时则不然，这表明丹参酮阻碍了酒精从胃肠道的吸收。最后，丹参酮未能影响酒精依赖大鼠酒精戒断综合征的严重程度。
本研究结果表明，在不同的过量饮酒实验模型中，丹参酮可能是丹参提取物降低酒精摄入量作用的活性成分。
