DBZ (Danshensu Bingpian Zhi), a Novel Natural Compound Derivative, Attenuates Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract

BackgroundDBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide‐induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages.Methods and ResultsThe effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E–deficient (apoE−/−) mice. For early treatment, 5‐week‐old apoE−/− mice were fed a Western diet and treated daily by oral gavage with or without DBZ or atorvastatin for 10 weeks. For advanced treatment, 5‐week‐old apoE−/− mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then they were randomly divided into 4 groups and subjected to the treatment of vehicle, 20 mg/kg per day DBZ, 40 mg/kg per day DBZ, or 10 mg/kg per day atorvastatin for the subsequent 10 weeks. We showed that early treatment of apoE−/− mice with DBZ markedly reduced atherosclerotic lesion formation by inhibiting inflammation and decreasing macrophage infiltration into the vessel wall. Treatment with DBZ also attenuated the progression of preestablished diet‐induced atherosclerotic plaques in apoE−/− mice. In addition, we showed that DBZ may affect LXR (liver X receptor) function and that treatment of macrophages with DBZ suppressed lipopolysaccharide‐stimulated cell migration and oxidized low‐density lipoprotein–induced foam cell formation.Conclusions DBZ potentially has antiatherosclerotic effects that involve the inhibition of inflammation, macrophage migration, leukocyte adhesion, and foam cell formation. These results suggest that DBZ may be used as a therapeutic agent for the prevention and treatment of atherosclerosis.

Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris

“…In vivo Matrigel assays showed that systemic administration of DBZ at low doses (0.2, 1, and 5 mg·kg −1 ·day −1 ) induced vascularization in Matrigel plug in C57BL/6 mice (Figure c–g). Interestingly, we also found DBZ (20 and 40 mg·kg −1 ·day −1 ) markedly reduced atherosclerotic lesion formation and attenuated the progression of pre‐established atherosclerotic plaques in ApoE −/− mice by inhibiting inflammation, macrophage migration, leukocyte adhesion, and foam cell formation (Wang et al, ). The discrepancy between DBZ's pro‐angiogenic effect and anti‐atherosclerosis effect is very likely to be due to a dose‐dependent pleiotropic modulation in response to different microenvironments and ongoing pathophysiology.…”

“…At relatively low concentrations of 10 −9 to 10 −7 M, DBZ produced an angiogenic phenotype in human endothelial cells. However, at higher concentrations of 5–20 × 10 −6 M, DBZ inhibited atherosclerosis by suppressing LPS‐stimulated macrophages migration and oxidized LDL‐induced foam cell formation (Wang et al, ). Besides, DBZ showed significant protective effects on vascular endothelial cell viability and tube formation against Hcy‐induced injury (Figure S2A–D), which has beneficial effect on atherosclerosis as well.…”

<p>Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages</p>

“…Previous studies have suggested that isoborneol has anti-inflammatory activity and its derivatives can prevent the formation of macrophage foam cells and intracellular lipid accumulation. 18 However, there are few studies investigating the role of isoborneol in the fight against atherosclerosis, such as the inhibition of the formation of macrophage-derived form cells. The present study found that isoborneol inhibited the accumulation of lipids and the uptake of ox-LDL in macrophages, which can prevent the formation of macrophage foam cells.…”

Tanshinol borneol ester on nanostructured lipid carriers has longer brain and systemic effector retention and better antioxidant activity in vivo

“…1 Previous studies have shown that DBZ is beneficial in patients with cardiovascular and cerebrovascular disease and that its therapeutic effects are better than either DSS or borneol alone. [2][3][4][5] Additionally, DBZ can be conveniently prepared for various dosage forms compared with a mixture of water-soluble DSS and water-insoluble borneol.…”