Molecular docking of anthocyanins constituents and HER-2 kinase domain / 生物工程学报

Anthocyanins are a ubiquitous group of water-soluble plant pigments of the flavonoid family, with anticancer property through HER-2 signaling pathway. Nowadays, molecular docking plays an important role in exposing the active sites and obtaining the bioactive conformation involving protein-ligand interactions. According to the crystal structure of HER-2 kinase domain and 12 main antitumor compounds of anthocyanins as well as ATP, a molecular docking study was performed by MVD program. All 12 compounds could bind to the same cavity of HER-2 kinase domain by high affinity (MolDock Score < -105 kJ/mol for anthocyanidins, < -130 kJ/mol for anthocyanidins-glc), where hydrophobic force and hydrogen bond played key roles. Additionally, this cavity overlapped with ATP binding (MolDock Score = -161 kJ/mol) domain; the binding of anthocyanins presumably interfered the H bond formation between ATP and HER-2. These results indicate that anthocyanins may competitively bind to ATP binding site in HER-2 kinase domain by suppressing HER-2 activation and downstream signaling cascade. This may provide useful theoretical instruction for the molecular mechanism of HER-2 kinase activity inhibition by anthocyanins in cancer prevention and treatment.

Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease, extent of angiographic coronary artery lesions and risk factors in the elderly / 中华老年医学杂志

Objective To observe the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2) levels and coronary artery disease (CAD), extent of angiographic coronary artery lesions and risk factors of CAD in the elderly. Methods Plasma levels of Lp-PLA2, triglyceride (TG), total cholesterol(TC), low density lipoprotein(LDL-C), high density lipoprotein cholesterol (HDL-C) and high sensitivity C-reactive protein(hs-CRP) were measured in 67 elderly patients with angiographic CAD meanwhile in 23 normal controls without angiographic coronary artery lesions. The extent of coronary artery lesions was evaluated according to the number of vessel lesions (divided into single, double and triple-vessel lesions) and Gensini scoring system. Then the relationship between Lp-PLA2 and CAD was assessed. Results The plasma levels of Lp-PLA2 were significantly higher in the CAD group than in the controls [(352.7 ± 129.0) vs. (204.0 ± 59. 7) μg/L, P < 0. 01]. Lp-PLA2 levels increased with the number of coronary artery lesions and Gensini score, then were positively correlated with age(r= 0. 25, P<0. 05) ,TC(r=0. 33, P<0. 01) ,LDL-C(r=0.27, P< 0. 05),apoB(r=0. 36, P<0. 01). The levels of LP-PLA2 and LP(a) were associated with CAD by using stepwise regression analysis. Conclusions In the eldly, the levels of LP-PLA2 are much higher in angiographic CAD, and these may reflect the severity of CAD. LP-PLA2 is a risk factor for CAD.