Abstract
The onsets of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in diabetics, especially in those with elevated homocysteine (Hcy), precede the development of cardiovascular (CV) events. Salvianic acid A (SAA) is a renowned Traditional Chinese Medicine (TCM) that has been applied in the treatment of cardiovascular disease for many decades. In this study, we aimed (1) to investigate the CV protective effects of SAA on ameliorating LVH and ED in db/db mice with elevated blood Hcy level and (2) to decipher whether the observed CV protective effects of SAA are associated with Hcy metabolism by modulating the methylation potential and redox status in the liver of the db/db mice with elevated blood Hcy level. Our results found that the administration of SAA could significantly slow down the build-up of left ventricular mass and ameliorate ED. Immunological assay analysis on the mouse liver tissue also indicated that SAA treatment on db/db mice with elevated Hcy was associated with reduced methylation potential but improved redox status. In conclusion, we revealed that SAA has the potential to protect against the hyperglycemia- and hyperhomocysteinemia-induced oxidative stress on diabetic mice via modulation in Hcy metabolism.
Highlights
In 2013, 382 million people in the world were living with diabetes mellitus (DM), and the figure is expected to rise drastically to about 600 million by 2035 [1]
The expected elevation of Hcy level after 8 wk of Salvianic acid A (SAA) cotreatment in the DM group was significantly reduced when compared to the DM group (Figure 3), implicating that DSS has a Hcy-lowering effect on this group
We found that the two diabetic groups without taking SAA treatment (DM and DM) exhibited increased PWd (58.5%, P < 0 01; 58.2%, P < 0 05), posterior wall thicknesses (PW) (31.6%, P < 0 05; 32.5%, P < 0 05), LVSd (38.1%, P < 0 05; 25.4%, P < 0 001), and left ventricular (LV) mass (49.0%, P < 0 001; 31.7%, P < 0 01) at the end of intervention period when compared to their baseline values (Table 2)
Summary
In 2013, 382 million people in the world were living with diabetes mellitus (DM), and the figure is expected to rise drastically to about 600 million by 2035 [1]. Recent evidences have shown that both long-term and short-term metformin treatments could lead to elevation of Hcy in type 2 DM patients due to reduction of serum folate and Vitamin B12 [9,10,11]. Today, both hyperglycemia and HHcy status have been recognized as strong cardiovascular disease (CVD) risk factors or predictors [12, 13], and HHcy status was strongly associated with the development of diabetes and diabetic CV complications [11, 14, 15]
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