Salvia Miltiorrhiza Root Water-Extract (Danshen) Has No Beneficial Effect on Cardiovascular Risk Factors. A Randomized Double-Blind Cross-Over Trial

Abstract

Purpose: Danshen is the dried root extract of the plant Salvia Miltiorrhiza and it is used as traditional Chinese medicinal herbal product to prevent and treat atherosclerosis. However, its efficacy has not been thoroughly investigated. This study evaluates the effect of Danshen on hyperlipidemia and hypertension, two well known risk factors for the development of atherosclerosis.

Methods: This was a randomized, placebo-controlled, double-blind crossover study performed at a tertiary referral center. Participants were recruited by newspaper advertisement and randomized to treatment with Danshen (water-extract of the Salvia Miltiorrhiza root) or placebo for 4 consecutive weeks. There was a wash out period of 4 weeks. Of the 20 analysed participants, 11 received placebo first. Inclusion criteria were: age 40-70 years, hyperlipidemia and hypertension. At the end of each treatment period, plasma lipids were determined (primary outcome), 24 hours ambulant blood pressure measurement (ABPM) was performed, and vasodilator endothelial function was assessed in the forearm.

Results: LDL cholesterol levels were 3.82±0.14 mmol/l after Danshen and 3.52±0.16 mmol/l after placebo treatment (mean±SE; p<0.05 for treatment effect corrected for baseline). Danshen treatment had no effect on blood pressure (ABPM 138/84 after Danshen and 136/87 after placebo treatment). These results were further substantiated by the observation that Danshen had neither an effect on endothelial function nor on markers of inflammation, oxidative stress, glucose metabolism, hemostasis and blood viscosity.

Conclusion: Four weeks of treatment with Danshen (water-extract) slightly increased LDL-cholesterol without affecting a wide variety of other risk markers. These observations do not support the use of Danshen to prevent or treat atherosclerosis.

Trial registration: ClinicalTrials.gov NCT01563770.

Conflict of interest statement

Competing Interests: For this study the authors received funding from a commercial source ‘Cinmar Pharma BV’. PB reports grants from Cinmar Pharma, during the conduct of the study. In addition, PB has founded a small company (Energeia Biosciences BV, Geertruidenberg, the Netherlands) and has a patent “Method for identifying modulators of BCRP/ABCG2-mediated ATP release and use of said modulators for treating diseases” pending. However, this patent is not related to the research in this manuscript, but is related to (plant-derived) immunomodulators based on modulation of BCRP/ABCG2-mediated ATP release, including TCM-derived compounds, such as Danshen-derived compounds. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flow diagram.

SAE: Serious Adverse Event. The SAE (Bell’s palsy) occurred during Danshen treatment (see text).

Fig 2. Graphic presentation of the study protocol.

Four weeks treatment with Danshen and placebo in a crossover design with at least four weeks of washout (represented in the figure as the period between week 4 and week 8). BP = blood pressure. ABPM = 24-h Ambulatory Blood Pressure Monitoring. TCM = traditional Chinese Medicine diagnosis.

Fig 3. Assessment of endothelial function.

Forearm blood flow in response to acetylcholine in the experimental arm (solid lines) and in the non experimental arm (dashed lines) in response to acetylcholine (left panel; dosage 0.5, 2.0, 8.0 μg.dl-1.min-1) and sodium nitroprusside (right panel; dosage 0.06, 0.20 and 0.60 μg.dl-1.min-1), during Danshen (dark grey circles) or placebo (light grey squares).

Fig 4. Results of the Nijmegen Hemostasis Assay.

A. Thrombin generation. B. Plasmin generation measured by fibrinolysis time.