|Title:||The cardiovascular protective role of salvianic acid A in diabetes with elevated homocysteine level|
|Advisors:||Lai, W. K. Christopher (HTI)|
|Subject:||Hong Kong Polytechnic University -- Dissertations|
Cardiovascular system -- Diseases
|Department:||Department of Health Technology and Informatics|
|Pages:||21, 200 pages : color illustrations|
|Abstract:||Cardiovascular disease (CVD) is the most common cause of death in people with diabetes mellitus (DM). Compared to the non-diabetic population, individuals with DM have a higher risk for left ventricular hypertrophy (LVH) and endothelial dysfunction (ED), especially for those comorbid with elevated homocysteine (Hcy) level. Few studies have addressed the effectiveness of traditional Chinese medicine (TCM) in relieving CVD burdens for diabetic patients with elevated Hcy level. Salvianic acid A (SAA) is an important ingredient extracted from Salvia Miltiorrhiza (Danshen) and has been widely applied in the treatment of CVD. A previous animal study indicated that SAA could ameliorate ED and lower the blood Hcy level in hyperhomocysteinemic rats without DM, but whether these observed beneficial effects might also be found in diabetic rodents remains unclear, particularly the effects on LVH and ED. Therefore, the primary aims of my thesis were to (1) investigate the protective effects of SAA against LVH and ED in db/db mice with elevated blood Hcy level, and (2) decipher whether the observed cardiovascular 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. A secondary objective of my thesis was to determine the antidiabetic activity of SAA, together with other structurally similar compounds. My findings suggest that an 8-week oral treatment of SAA can significantly slow the progression of left ventricular mass in the DM group compared to other DM groups without SAA. Moreover, the chronic SAA administration ameliorated ED in the diabetic mice with elevated Hcy level. In another ex vivo experiment, we found that SAA was able to induce vasorelaxation via a calcium channel-dependent pathway. Furthermore, the serum Hcy level in the methionine-diet DM group that received SAA treatment for 8 weeks was significantly reduced compared to the methionine-diet DM group without taking SAA treatment, along with an increased level of glutathione production in their liver. Lastly, I found that SAA was not a good antidiabetic agent. However, some compounds that could be extracted from S. Miltiorrhiza, such as Salvianolic Acid A and Salvianolic Acid B, were structurally similar to that of SAA but possessing better antidiabetic potential than SAA. In conclusion, my thesis underlines the protective effects of SAA treatment against LVH and ED in diabetic mice with elevated Hcy. These observed beneficial effects are likely due to an improved redox status induced by the antioxidant effect of SAA itself, and to a certain extent associated with increased production of glutathione via activated trans-sulphuration pathway.|
|Rights:||All rights reserved|
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