Salvialba acid (1) with a novel abietane norditerpenoid skeleton and 2-hydroxydihydrotanshinone I (2), a new abietane norditerpenoid, were isolated from Salvia miltiorrhiza var. alba. Their structures were elucidated by spectroscopic analysis and X-ray diffraction. The absolute configuration of 1 was determined by an electronic circular dichroism (ECD) experiment and TDDFT ECD computations. A possible biosynthesis pathway is proposed for 1. Compounds 1 and 2 were demonstrated to have anti-inflammatory effects on vascular inflammation induced by TNF-α in human aortic endothelial cells (HAECs).

Ethnopharmacological relevanceSalvia miltiorrhiza var. alba roots are used as the Chinese traditional medicine Danshen for the treatment of cardiovascular diseases in local clinical practice. Tanshinones are the major effective constituents of S. miltiorrhiza var. alba roots, but only tanshinone IIA, tanshinone I, cryptotanshinone, and 15,16-dihydrotanshinone have been investigated for their anti-inflammatory activities.Materials and methodsEleven known compounds were isolated from S. miltiorrhiza var. alba roots, and the structures of all compounds were elucidated by spectroscopic analysis and comparisons with reported data. Immune anti-inflammatory activities were assessed by the ability to inhibit the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin (IL)-8 using enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was also used to compare the inhibitory effects of the compounds on TNF-α, IL-1β, and IL-8 mRNA expression with that of tanshinone IIA in lipopolysaccharide-stimulated THP-1 macrophages.ResultsAll tanshinones, except for compound 5, significantly inhibited the mRNA and protein expression of TNF-α, IL-1β, and IL-8, and their anti-inflammatory activities were stronger than that of tanshinone IIA. Compound 9 (5 μM) showed the highest inhibitory effects for TNF-α, IL-1β, and IL-8, at 56.3%, 67.6%, and 51.7%, respectively.ConclusionsTen of the 11 tanshinones were shown to have anti-inflammatory properties superior to those of TSIIA, and which significantly inhibited the expression of TNF-α, IL-1β, and IL-8. The present results provided a referential basis for explaining the use of S. miltiorrhiza var. alba root as a Chinese folk medicine for treating cardiovascular diseases associated with inflammation, and show the importance of trace constituents of this herb.Download high-res image (244KB)Download full-size image

Salvianolic acid A (Sal A), an important constituent of Radix Salviae Miltiorrhizae (RSM), is effective for the treatment of myocardial infarction (MI) and coronary heart disease due to its potential in the improvement of acute myocardial ischemia. However, its content is very low in RSM. So it is obvious to find a rich source of Sal A or to improve its content by conversion of other related components into Sal A modifying reaction conditions. In this research we focused on the conversion of Sal B into Sal A in aqueous solutions of RSM by using different reaction conditions including pH, temperature, pressure and humidity. During the reactions, the contents of Sal A, Sal B and danshensu in the RSM were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LCMS). The results indicated that the conversion of Sal B into Sal A in RSM tissues under the conditions of a high temperature, high pressure and high humidity was efficient and thereby, was readily utilized to prepare rich Sal A materials in practice.Download high-res image (172KB)Download full-size image