TY - JOUR
T1 - Puerarin suppresses macrophage activation via antioxidant mechanisms in a CaPO4-induced mouse model of aneurysm
AU - Tanaka, Teruyoshi
AU - Moriyama, Tatsuya
AU - Kawamura, Yukio
AU - Yamanouchi, Dai
N1 - Publisher Copyright:
© 2016, Center for Academic Publications Japan. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Aneurysm is characterized by balloon-like expansion of the arterial wall and eventual rupture of the aorta. The pathogenesis of aneurysm is associated with the degradation of matrix proteins by matrix metalloproteinases (MMPs) produced by activated macrophages. Although aneurysm is associated with significant mortality and morbidity, surgical intervention is the only proven treatment strategy. Therefore, development of therapeutic agents for aneurysm is greatly anticipated. Here, we demonstrated the protective effects of the major isoflavone puerarin, which is found in kudzu roots and vines. Aneurysms were surgically induced in ten-wk-old male mice using CaPO4. Subsequently, animals were intra-peritoneally injected daily with puerarin at 2.5 mg/kg body weight or with vehicle alone for 2 wk. CaPO4-induced aneurysm was significantly suppressed by puerarin administration. In subsequent macrophage activation assays using Tumor necrosis factor (TNF) and CaPO4 crystals in vitro, puerarin decreased Mmp9 mRNA expression and secreted protein levels. Moreover, induction of IB, ERK, and p38 phosphorylation by TNFα and CaPO4 in macrophages was suppressed by puerarin treatments. Finally, puerarin attenuated reactive oxygen species production, following induction by TNF and CaPO4. Taken together, the present data demonstrate that puerarin suppresses macrophage activation by inhibiting IB, ERK, and p38 activity and reactive oxygen species production in a CaPO4-induced mouse model of aneurysm.
AB - Aneurysm is characterized by balloon-like expansion of the arterial wall and eventual rupture of the aorta. The pathogenesis of aneurysm is associated with the degradation of matrix proteins by matrix metalloproteinases (MMPs) produced by activated macrophages. Although aneurysm is associated with significant mortality and morbidity, surgical intervention is the only proven treatment strategy. Therefore, development of therapeutic agents for aneurysm is greatly anticipated. Here, we demonstrated the protective effects of the major isoflavone puerarin, which is found in kudzu roots and vines. Aneurysms were surgically induced in ten-wk-old male mice using CaPO4. Subsequently, animals were intra-peritoneally injected daily with puerarin at 2.5 mg/kg body weight or with vehicle alone for 2 wk. CaPO4-induced aneurysm was significantly suppressed by puerarin administration. In subsequent macrophage activation assays using Tumor necrosis factor (TNF) and CaPO4 crystals in vitro, puerarin decreased Mmp9 mRNA expression and secreted protein levels. Moreover, induction of IB, ERK, and p38 phosphorylation by TNFα and CaPO4 in macrophages was suppressed by puerarin treatments. Finally, puerarin attenuated reactive oxygen species production, following induction by TNF and CaPO4. Taken together, the present data demonstrate that puerarin suppresses macrophage activation by inhibiting IB, ERK, and p38 activity and reactive oxygen species production in a CaPO4-induced mouse model of aneurysm.
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U2 - 10.3177/jnsv.62.425
DO - 10.3177/jnsv.62.425
M3 - Article
C2 - 28202848
AN - SCOPUS:85012985990
SN - 0301-4800
VL - 62
SP - 425
EP - 431
JO - Journal of Nutritional Science and Vitaminology
JF - Journal of Nutritional Science and Vitaminology
IS - 6
ER -