l-Tetrahydropalmatine, an active component of Corydalis yanhusuo W.T. Wang, protects against myocardial ischaemia-reperfusion injury in rats.
l-Tetrahydropalmatine (l-THP) is an active ingredients of Corydalis yanhusuo W.T. Wang, which protects against acute global cerebral ischaemia-reperfusion injury. In this study, we show that l-THP is cardioprotective in myocardial ischaemia-reperfusion injury and examined the mechanism. Rats were treated with l-THP (0, 10, 20, 40 mg/kg b.w.) for 20 min before occlusion of the left anterior descending coronary artery and subjected to myocardial ischaemia-reperfusion (30 min/6 h). Compared with vehicle-treated animals, the infarct area/risk area (IA/RA) of l-THP (20, 40 mg/kg b.w.) treated rats was reduced, whilst l-THP (10 mg/kg b.w.) had no significant effect. Cardiac function was improved in l-THP-treated rats whilst plasma creatine kinase activity declined. Following treatment with l-THP (20 mg/kg b.w.), subunit of phosphatidylinositol 3-kinase p85, serine(473) phosphorylation of Akt and serine(1177) phosphorylation of endothelial NO synthase (eNOS) increased in myocardium, whilst expression of inducible NO synthase (iNOS) decreased. However, the expression of HIF-1α and VEGF were increased in I(30 min)R(6 h), but decreased to normal level in I(30 min)R(24 h), while treatment with l-THP (20 mg/kg b.w.) enhanced the levels of these two genes in I(30 min)R(24 h). Production of NO in myocardium and plasma, activity of myeloperoxidase (MPO) in plasma and the expression of tumour necrosis factor-α (TNF-α) in myocardium were decreased by l-THP. TUNEL assay revealed that l-THP (20 mg/kg b.w.) reduced apoptosis in myocardium. Thus, we show that l-THP activates the PI3K/Akt/eNOS/NO pathway and increases expression of HIF-1α and VEGF, whilst depressing iNOS-derived NO production in myocardium. This effect may decrease the accumulation of inflammatory factors, including TNF-α and MPO, and lessen the extent of apoptosis, therefore contributing to the cardioprotective effects of l-THP in myocardial ischaemia-reperfusion injury.
Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yi
Y
Han
Wen
W
Zhang
Yan
Y
Tang
Wenli
W
Bai
Fan
F
Yang
Liping
L
Xie
Xiaozhen
X
Li
Suming
S
Zhou
Shiyang
S
Pan
Qi
Q
Chen
Albert
A
Ferro
Yong
Y
Ji
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D031311:Corydalis / Q000737:chemistry*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000889:Anti-Arrhythmia Agents; D001600:Berberine Alkaloids; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; C014215:tetrahydropalmatine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt