Melatonin enhances atherosclerotic plaque stability by inducing prolyl-4-hydroxylase α1 expression.

OBJECTIVE: Melatonin, an endogenous neurohormone secreted predominately by the pineal gland, has a variety of physiological functions. However, its protective role in atherosclerosis is not clear. In this study, we sought to investigate the potential effects of melatonin in modulating atherosclerotic plaque stability in apolipoprotein E knockout (ApoE) mice. METHOD AND RESULTS: Smooth muscle cells were treated with melatonin, which significantly increased mRNA and protein levels of a key intracellular enzyme essential for collagen maturation and secretion, prolyl-4-hydroxylase α1 (P4Hα1). Mechanistically, melatonin increased Akt phosphorylation and transcriptional activation of specificity protein 1 (Sp1), which bound with the P4Hα1 promoter and then induced P4Hα1 expression. Pretreatment with either Akt inhibitor LY294002 or Sp1 inhibitor mithramycin A (MTM) could inhibit melatonin-induced P4Hα1 expression. Finally, atherosclerotic lesions were induced by placing a perivascular collar on the right common carotid artery of ApoE mice, which were received with or without different doses of melatonin or MTM. High-dose melatonin enhanced atherosclerotic plaque stability in ApoE mice in vivo by inducing the expression of P4Hα1, which was reversed by MTM. CONCLUSION: We propose that melatonin supplementation may provide a novel and promising approach to atherosclerosis treatment.

Systematic review and meta analysis of randomized controlled trials on Tianmagouteng decoction in treatment of primary hypertension with liver Yang hyperactivity syndrome.

OBJECTIVE: To assess the efficacy of Tianmagouteng decoction in the treatment of primary hypertension with liver yang hyperactivity syndrome. METHODS: The databases of MEDLINE (1950-2012), EMbase (1980-2012), China biology medicine (CBM) (1994-2012), China national knowledge infrastructure (CNKI) (1989-2012), Weipu (VIP) (1995-2012) and Wanfang (1989-2012) were searched and we performed manual searches for conference proceedings to select randomized controlled trials (RCTs) on Tianmagouteng decoction for the treatment of primary hypertension with liver Yang hyperactivity syndrome. Studies were enrolled according to the study-selecting criteria. The methodological quality was evaluated, data were extracted and meta-analyses were conducted with RevMan 4.2 software. RESULTS: Nine RCTs were selected involving 784 patients with no significant difference in decrease in systolic blood pressure (SBP) [OR = 1.02, 95% CI (-0.24, 2.29), P = 0.10] and diastolic blood pressure (DBP) [OR = 0.56, 95% CI (-0.10,1.23), P = 0.11] between the Tianmagouteng group and the control group. While there was a significantly larger increase in serum superoxide dismutase (SOD) [OR = 6.26, 95% CI (1.27,11.66), P = 0. 01] in the Tianmagouteng group than that in the control group. CONCLUSION: Tianmagouteng decoction can decrease both systolic and diastolic blood pressure and greatly increase serum SOD. Due to poor quality of included studies, the efficacy needs to be further assessed.