Tetramethylpyrazine attenuates atherosclerosis development and protects endothelial cells from ox-LDL.
OBJECTIVE
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.


CONCLUSIONS
TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.
Department of Cadre Ward No. 3, the General Hospital of Jinan Military Area Command of PLA, Jinan, China.
Guo-feng
GF
Wang
Cui-ge
CG
Shi
Mu-zhen
MZ
Sun
Lei
L
Wang
Shu-xia
SX
Wu
Hao-feng
HF
Wang
Zhi-qing
ZQ
Xu
Dong-mei
DM
Chen
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects*; D007150:Immunohistochemistry; D030004:Ligusticum / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D008297:Male; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011719:Pyrazines / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D011719:Pyrazines; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol; C017953:tetramethylpyrazine