Effects of 3,4-dihydroxyacetophenone on the hypercholesterolemia-induced atherosclerotic rabbits.

Abstract

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.

• Authors: Daijuan Zhang, Jiangyue Liu, Lin Wang, Jianying Wang, Wentao Li, Baoxiang Zhuang, Jianping Hou, Tongmei Liu
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 36 Issue 5 Pg. 733-40 ( 2013) ISSN: 1347-5215 [Electronic] Japan
• PMID: 23412669 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Anti-Inflammatory Agents
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• 3,4-dihydroxyacetophenone
• Alanine Transaminase

Topics

• Acetophenones (pharmacology)
• Alanine Transaminase (blood)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Aorta (pathology)
• Atherosclerosis (etiology, metabolism, pathology)
• Hypercholesterolemia (complications, metabolism, pathology)
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Muscle, Smooth, Vascular (pathology)
• RNA, Messenger (metabolism)
• Rabbits
• Tumor Necrosis Factor-alpha (blood)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)