Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL

• Published in: Cardiovascular drugs and therapy 2013-06, Vol.27 (3), p.199-210
• Main Authors: Wang, Guo-feng, Shi, Cui-ge, Sun, Mu-zhen, Wang, Lei, Wu, Shu-xia, Wang, Hao-feng, Xu, Zhi-qing, Chen, Dong-mei
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Abdominal - drug effects; Aorta, Abdominal - pathology; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Cardiology; Cardiology. Vascular system; Cardiovascular system; Cell Adhesion - drug effects; Cell Culture Techniques; Cell Movement - drug effects; Cells, Cultured; Cholesterol - blood; Cholesterol, Dietary - administration & dosage; Disease Models, Animal; Endothelial Cells - drug effects; Immunohistochemistry; Ligusticum - chemistry; Lipoproteins, LDL - adverse effects; Male; Medical sciences; Medicine; Medicine & Public Health; Original Article; Pharmacology. Drug treatments; Plaque, Atherosclerotic - blood; Plaque, Atherosclerotic - pathology; Plaque, Atherosclerotic - prevention & control; Pyrazines - administration & dosage; Pyrazines - isolation & purification; Pyrazines - therapeutic use; Rabbits; Rats; Rats, Sprague-Dawley; Triglycerides - blood
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-013-6440-6

Purpose We assessed whether tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii Franchat , attenuates atherosclerosis (AS) development in rabbits and protects endothelial cells injured by ox-LDL. Methods In vivo, rabbits subjected to atherosclerosis were treated with TMP (75 and 150 mg/kg) by oral gavage for 12 weeks. In vitro, rat aortic endothelial cells (RAECs) were stimulated by ox-LDL. Results TMP treatment with 75 and 150 mg/kg significantly reduced the relative atherosclerosis area ratio in the aorta (0.41 ± 0.042, 0.27 ± 0.047 vs. 0.66 ± 0.058 in AS), the ratio of intimal/medial thickness (0.54 ± 0.09, 0.39 ± 0.07 vs. 1.1 ± 0.3 in AS) and the number of monocytes in intimal (10.1 ± 2.8, 8.2 ± 2.0 vs. 14.1 ± 4.9 counts/mm 2 in AS). TMP also decreased levels of TC (15 ± 4.2 to 6.1 ± 1.2 mmol/L), TG (1.8 ± 0.3 to 1.08 ± 0.24 mmol/L), LDL-C (20.1 ± 4.3 to 10.2 ± 1.6 mmol/L) and increased HDL-C levels (0.40 ± 0.08 to 0.85 ± 0.17 mmol/L) in atherosclerosis rabbit plasma. TMP decreased the MCP-1 (187.3 ± 38.4 to 86.1 ± 17.2 pg/ml) and ICAM-1 (350.6 ± 43.7 to 260.6 ± 46.1 pg/ml) levels in plasma and inhibited LOX-1 expression in the rabbit aortas. Moreover, our in vitro study revealed that TMP suppressed monocyte adhesion to RAECs, inhibited RAEC migration, and down-regulated MCP-1 and ICAM-1 expression in ox-LDL-injured RAECs. Likewise, TMP inhibited LOX-1 and 5-LOX expression, and prevented nuclear accumulation of RelA/p65 and IκB degradation in ox-LDL-injured RAECs. Furthermore, TMP suppressed ox-LDL-induced activations of p-ERK, p-p38, and p-JNK MAPK. Conclusion TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.