The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry

Abstract

Tanshinol borneol ester (DBZ) is a novel experimental compound that consists of two chemical structural units from danshensu and borneol. It exhibits efficacious anti-ischemic and anti-atherosclerosis activities in rats. A fecal metabolomics based on Liquid Chromatography-Mass Spectrometry combined with clinical histopathology and blood lipid estimation was employed to assess the efficacy and the metabolic changes caused by administration of DBZ in atherosclerotic rats. There were the typical pathological features of atherosclerosis and significantly increased levels of TC, TG and LDL-C in the atherosclerotic rat group. Nevertheless, atherosclerotic rats administered both DBZ (at a dose of 40 mg kg(-1)) and simvastatin (at a dose of 20 mg kg(-1)) showed good therapeutic effects. The results of the metabolomics studies showed that 55 differential metabolites such as sebacic acid, enterodiol, nonanedioic acid, dodecanedioic acid, cholic acid, 13(S)-HPODE, deoxycholic acid, some phosphatidylglycerol and phosphatidic acids were found, indicating that abnormal metabolism occurred in the pathways of fatty acid oxidation, linoleic acid metabolism, bile acid biosynthesis and glycerophospholipid metabolism in atherosclerotic rats. Compared to those in the model group, the contents of 41 differential metabolites showed a tendency to recover to a healthy level after DBZ administration. Metabolomics studies suggested that DBZ exhibited good treatment efficacy against atherosclerosis by adjusting disturbed metabolic pathways related to atherosclerosis. This study could provide an experimental basis for DBZ's application to act as a candidate drug with anti-atherosclerosis activity.

Investigation of novel metabolites potentially involved in the pathogenesis of coronary heart disease using a UHPLC-QTOF/MS-based metabolomics approach

“…Regarding phosphatidylglycerol (PGs), which a phosphoglycerol moiety occupies a glycerol substitution site, little evidence has been shown on their relationship with CHD, and we were the first to reveal a positive relationship between PG ( 20:3/2:0) and CHD (OR: 3.938; 95% CI: (1.891, 8.204); P = 0.0001) in human plasma. Several previous studies have provided evidence that PGs are significantly increased in atherosclerotic rats 45 , 46 . Elevated levels of PGs were also found in patients with type 2 diabetes and prediabetes 47 .…”

Metabolite identification of tanshinol borneol ester in rats by high‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…DBZ was dissolved in 2% Kolliphor ® P 188 to give a final concentration of 4.0 mg/mL. The solutions were administered to the rats via intravenous injection with a dosage of 20 mg/kg (Jia et al, ).…”

“…It has been proved that DBZ can promote angiogenesis through activating Akt and MAPK signalling pathways (Liao, Fan, Zhao, Choi, & Zheng, ). In addition, DBZ exhibits distinct anti‐atherosclerosis effects (Jia et al, ), suppresses lipopolysaccharide‐induced macrophage activation and lipid accumulation in vitro (Xie et al, ), and reduces atherosclerotic lesion formation by inhibiting inflammation and decreasing macrophage infiltration into the vessel wall of apolipoprote E‐deficient mice (Wang et al, ). The investigations above suggest that DBZ will become a promising new drug for treating cardio‐cerebrovascular diseases.…”

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.…”