Quantitative proteomics reveals Shexiang Baoxin Pill exerts cardioprotective effects by preserving energy metabolism in a rat model of myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a composite formula of traditional Chinese medicine used to treat cardiovascular disease (CVD) in the clinic. However, the mechanism of its therapeutic effect on CVD has not been clearly elucidated yet. AIM OF THE STUDY: The aim of this study was to investigate the potential cardioprotective mechanism of SBP in the treatment of myocardial infarction (MI) model rats by applying proteomic approach. MATERIALS AND METHODS: The rat model of MI was generated by ligating the left anterior descending coronary artery. Eighteen rats were randomly divided into three groups (n = 6 each): the MI group, MI group treated with SBP (SBP), and sham-operated group (SOG). Cardiac function in the experimental groups was assessed by echocardiography analyses after 15 days of treatment. A label-free quantitative proteomic approach was utilized to investigate the whole proteomes of heart tissues from the groups above on the day of the operation (Day 0) and 15 days later (Day 15). The differentially expressed proteins were subsequently analyzed with bioinformatic methods. Additionally, the expression levels of two promising proteins were validated by Western blotting. RESULTS: The echocardiography analyses showed that SBP treatment significantly preserved the cardiac function of MI rats. Additionally, quantitative proteomics identified 389 differentially expressed proteins, and 15 proteins were considered as logical candidates for explaining the cardioprotective effect of SBP. Bioinformatic analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatment, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) were significantly downregulated in the MI model group compared with the SOG group and returned to the basal level with SBP treatment, confirmed by Western blotting. CONCLUSIONS: The results of our study suggest that the cardioprotective effects of SBP are achieved through the preservation of energy metabolism in the heart tissue of MI rats.

Manganese in blood cells as an exposure biomarker in manganese-exposed workers healthy cohort.

Elevated exposure to manganese (Mn) has long been a public health concern. However, there is currently no consensus on the best exposure biomarker. Here we aimed to investigate the exposomic characteristics of plasma metals among Mn-exposed workers and explore the potential biomarkers of Mn exposure in the blood pool. First, total sixteen plasma metals (Calcium, Magnesium, Iron, Zinc, Copper, Selenium, Lead, Chromium, Arsenic, Manganese, Nickel, Molybdenum, Cadmium, Mercury, Thallium, and Cobalt) were determined among 40 occupationally Mn-exposed subjects. Second, Mn levels in both plasma and blood cells were detected among 234 workers from the manganese-exposed workers healthy cohort (MEWHC), respectively. Analysis of plasma metal exposome showed that the plasma Mn concentrations were positively correlated to plasma Fe (r=0.361), Ni (r=0.363), Cr (r=0.486), and Hg (r=0.313) (all p<0.05). Mn concentrations in plasma were not significantly correlated to external exposure levels (ptrend=0.200), and it was further confirmed among the 234 subjects (ptrend=0.452). However, Mn concentrations in blood cells progressively increased as the external exposure dose increased (low-exposure group vs high-exposure group, median 11.53µg/L vs 20.41µg/L, ptrend=0.001). Our results suggest that Mn in blood cells, but not plasma, could serve as a potential internal exposure biomarker. Larger validation studies are needed to establish the utility of this biomarker.