2 in persons with existing CVD [2]. There is some evidence that measures, which reduce circulating levels of adhesion molecules also reduce cardiovascular risk [8, 9]. The use of herbs and herbal therapies in Western societies is extensive and increasing, especially for the prevention of illness and the management of chronic disease. Radix Salviae Miltiorrhizae (Chinese herb Dan Shen) and Radix Notoginseng (San Qi) are medicinal herbs (material medica) commonly used in traditional Chinese medicine practice to prevent or treat conditions relating to the heart and blood vessels. A mixture of these two herbs, together with a third materia medica—Borneolum Syntheticum (Bing Pian)—is produced by the Tianjin Tasly Pharmaceutical Co., Ltd, Tianjin, China, under the name of the “Dantonic Pill” (DP) (also known as the “Cardiotonic Pill”), under conditions of “Good Manufacturing Practice” (GMP) and “Good Laboratory Practice” (GLP) veriﬁed by Chinese, Australian and US Government agencies. This product has been sold in China for ∼8 years, predominantly for the prevention and treatment of CVD [10]. Laboratory studies have shown that this product displays a range of activities in the cardiovascular system, including reduction in venous thrombosis [11] and blood viscosity [12]. We have previously shown that in cultured human vascular endothelial cells DP signiﬁcantly attenuates tumor necrosis factor α-induced expression of adhesion molecules ICAM-1 and VCAM-1 in a dose-dependent manner and inhibits platelet-derived growth factor BB-induced DNA synthesis and cell proliferation in cultured human vascular smooth muscle cells [13, 14]. In addition, we have found that in a mouse model of atherosclerosis—apolipoprotein E deﬁcient mice fed an atherogenic diet—administration of DP prevents increases in VCAM-1 expression and inhibits the development of fatty streaks and atherosclerotic plaques in the thoracic aorta without altering levels of circulating lipids [15]. The study reported here was designed to examine the eﬀects of DP on expression of adhesion molecules in human subjects with mild to moderate hypercholesterolemia and to obtain data about the tolerability and safety of this product in a Western population. 2. Methods 2.1. Study Design and Participants. The study employed a parallel double-blinded, randomized, placebo controlled design. Forty subjects with mild to moderately elevated cholesterol were randomly allocated to receive either DP or matching placebo for 12 weeks. The study was part of a larger investigation of the eﬀects of Chinese medicinal herbs on cardiovascular risk, other aspects of which will be reported elsewhere. The study was carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. Participants were healthy individuals aged 18 years and over with a total plasma cholesterol of 5.0 mmol/l or above, triglyceride level of >2 mmol/l or HDL level of <1.0 mmol/l. Exclusion criteria included plasma triglyceride levels over Evidence-Based Complementary and Alternative Medicine 10 mmol/l, established heart disease, other serious medical or psychological conditions, pregnancy, current use of vasoac- tive medications, warfarin and postmenopausal hormone therapy. Participants taking omega-3 ﬁsh oil supplements were asked to cease these at least 3 weeks prior to entering the study. Participants were recruited via newspaper adver- tisements and posters displayed at the Alfred Hospital in Melbourne, Australia. Ethics approval was obtained from the Alfred Hospital Ethics Committee and Monash University and all participants gave full consent. Following baseline assessment (Visit 1) participants were randomized to receive either DP or placebo in capsule form, three capsules three times per day for 12 weeks, after which the assessment was repeated (Visit 2). Participants were asked to maintain their current diets and exercise regimes during the study period. They were contacted by telephone every 3 weeks to ascertain side eﬀects and encourage compliance, which was assessed by examination of unused returned packets. They were also asked to complete a 4-day diet diary and exercise questionnaire during the ﬁrst and last weeks of the study. 2.2. Outcome Variables. The primary outcome variables were circulating levels of ICAM-1, VCAM-1 and E-selectin. Secondary outcomes included serum urea, electrolytes, crea- tinine, glucose, liver function, lipids, full blood examination and high-sensitivity C-reactive protein. 2.3. Chinese Herbal Mixture. The DP is an herbal product produced by Tianjin Tasly Pharmaceutical Corporation Ltd in China consisting of a mixture of three Chinese materia medica: Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum. Both the preparation and the individual herbs have been approved by the Australian Therapeutic Goods Administration for use in Australia and are widely available. Animal toxicity studies of the DP conducted in China and reported by the Tianjin Tasly Pharmaceutical Company demonstrated no toxic eﬀects in mice in studies up to 6 months duration. The lethal dosage (LD50) of DP extract was assessed via single gastric canal on mice and was calculated using the “Bliss Method” as recommended in the Chinese Government’s New Drug (Chinese Medicine) Pre- Clinical Research Guidelines [16]. The LD50 was found to be 25.807 g/kg, equivalent to 3934 times the intended clinical human oral dose of 6.56 mg/kg. 2.4. Laboratory Techniques. Expression of ICAM-1, VCAM- 1 and E-selectin in circulating leukocytes was determined by ﬂuorescence-activated cell sorting (FACS) analysis. Whole blood cells were collected after separation of the plasma, incubated in the lysis buﬀer (BD Pharm Lyse (Cat. No. 555899), BD Biosciences Pharmingen, San Diego, CA, USA) for 10 min at 37◦C and washed in PBS to remove the red blood cells, and the leukocytes were re-suspended in 0.5 mL Hanks’ balanced salt solution (HBSS). Cells were incubated with a speciﬁc ﬂuorescence-connected antibody against ICAM-1, VCAM-1 or E-selectin (BD Biosciences,