Imperatorin (
IMP) is an active
furocoumarin in the
traditional Chinese medicine Angelica dahurica and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of
IMP on blood pressure (BP) and
antioxidant effects in spontaneously hypertensive rats (SHR) and human embryonic kidney 293 cells. SHR were administered
IMP (6.25, 12.5, and 25 mg/kg/d) or
tempol (18 mg/kg/d) daily by gavage for 12 weeks.
Thiobarbituric acid-reactive substances,
proteinuria levels, and
superoxide dismutase activity were evaluated with commercial kits.
Nicotinamide adenine dinucleotide phosphate (
NADPH) oxidase subunits of the renal cortical tissues were determined by
reverse transcriptase polymerase chain reaction and Western blot. Twenty-four hour urinary 8-Iso-prostaglandin F2α was measured by
enzyme linked
immunosorbent assay. Systolic BP and diastolic BP were significantly reduced by treatment with
IMP (6.25, 12.5, and 25 mg/kg/d) in SHR. Meanwhile, we found that renal cortical
superoxide dismutase activities were significantly increased in
IMP-treated groups. Renal cortical and urinary
thiobarbituric acid-reactive substances' levels, the 24-hour urinary excretion of 8-Iso-prostaglandin F2α, and
proteinuria in the
IMP-treated group, were lower than SHR group. After that, we found the
messenger RNA expressions and
protein levels of
NADPH oxidase subunits were markedly reduced after
IMP treated in SHR.
IMP also reduced the phosphorylation of
protein kinase B, extracellular signal-regulated kinase1/2,
p38 mitogen-activated protein kinase (MAPK), and
c-Jun N-terminal kinase in renal cortical in SHR. In addition, H2O2-induced ROS production in human embryonic kidney 293 cells was markedly attenuated by
IMP. H2O2-induced activation of MAPK,
protein kinase B, and expression of
NADPH oxidase were also attenuated by pretreatment of
IMP. In summary,
IMP showed
antihypertensive effect via prevention of renal injury not only by reducing
NADPH oxidase but also by inhibiting of MAPK pathway.