Effects of 3,4-Dihydroxyacetophenone on the Hypercholesterolemia-Induced Atherosclerotic Rabbits

• Published in: Biological & pharmaceutical bulletin Vol. 36; no. 5; pp. 733 - 740
• Main Authors: Zhang, Daijuan, Liu, Jiangyue, Wang, Lin, Wang, Jianying, Li, Wentao, Zhuang, Baoxiang, Hou, Jianping, Liu, Tongmei
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.05.2013; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: 3,4-dihydroxyacetophenone; Acetophenones - pharmacology; Alanine Transaminase - blood; Animals; Anti-Inflammatory Agents - pharmacology; Aorta - pathology; atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Hypercholesterolemia - complications; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Lipid Metabolism - drug effects; Liver - drug effects; Liver - metabolism; Macrophages - drug effects; Macrophages - metabolism; Male; Muscle, Smooth, Vascular - pathology; Rabbits; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - blood; vascular cell adhesion molecule-1; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b12-00710

3,4-Dihydroxyacetophenone (3,4-DHAP) is one herbal extract from bald Mao-dong-qing leaves. We reported that 3,4-DHAP had anti-inflammatory function by decreasing tumor necrosis factor-α (TNF-α) secretion in macrophages. The aim of the study was to examine the effects of 3,4-DHAP on plasma and liver lipids, plasma alanine aminotranferase (ALT) and TNF-α level, vascular cell adhesion molecule-1 (VCAM-1) expression, plaque vulnerability and vascular inflammation in hypercholesterolemia-induced atherosclerotic rabbits. Male New Zealand white rabbits were randomized into negative control, positive control, 3,4-DHAP and simvastatin groups. From weeks 2 to 12, the rabbits were treated with 3,4-DHAP or simvastatin. At weeks 12, all the animals were sacrificed. Plasma lipids and ALT were measured using the enzymatic endpoint method. Plasma TNF-α was measured using enzyme-linked immuno sorbent assay (ELISA). Liver lipids concentrations were estimated using commercial kits. The expression of VCAM-1 was measured using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Histological analysis was used to evaluate the pathologic changes of rabbit aortas. The results showed that 3,4-DHAP markedly lowered plasma and liver lipids, lowered plasma ALT and TNF-α levels compared with the positive control group. VCAM-1 mRNA and protein were markedly inhibited by 3,4-DHAP. Decreased aortic plaque instability was evident in 3,4-DHAP-treated rabbits, as demonstrated by a thickened elastic layer, increased vascular smooth muscle cells (VSMCs) accumulation in the plaques, less neointima hyperplasia and macrophages recruitment. 3,4-DHAP may attenuate the progression of atherosclerotic lesions and stabilize plaques by lowering plasma lipids, the number of macrophages and the expression of VCAM-1, while increasing the number of VSMCs in the atherosclerotic plaques.