This study investigated the effect of
sesamin on myocardial
fibrosis in spontaneously hypertensive rats (SHRs) and the possible mechanisms involved. Twenty-eight male SHRs were randomly allocated to SHR group, Ses160 group (
sesamin 160 mg/kg), Ses80 group (
sesamin 80 mg/kg) and Cap30 group (
captopril 30 mg/kg). Seven male WKY rats were used as control.
Sesamin and
captopril were administered intragastrically for 12 weeks.
Captopril significantly reduced systolic blood pressure and
angiotensin II (Ang II) levels in SHRs, accompanied by a marked attenuation of
left ventricular hypertrophy (LVH) and
collagen deposition (P <0.05 or P <0.01). Though
sesamin had no significant influence on Ang II levels, and the hypotensive effect was also significantly inferior to that of
captopril (P <0.05 or P <0.01), however, the improvement of LVH and
collagen deposition was similar to that in
captopril group.
Sesamin markedly reduced transforming growth factor-β1 (TGF-β1) content in cardiac tissues, with Smad3 phosphorylation decreased and
Smad7 protein expression increased notably (P <0.05 or P <0.01).
Protein expression of
type I collagen and
type III collagen, target genes of Smad3, was down-regulated markedly by
sesamin (P <0.05 or P <0.01). In addition,
sesamin significantly increased total
antioxidant capacity and
superoxide dismutase protein in cardiac tissues (P <0.05 or P <0.01), while the expression of
NADPH oxidase subunit p47phox and
malondialdehyde content were reduced markedly (P <0.05 or P <0.01). In vitro studies also demonstrated that
sesamin was able to suppress Ang II induced phosphorylation of Smad3 and secretion of TGF-β1 and type I and
type III collagen in cultured rat cardiac fibroblasts. These data suggest that
sesamin is capable of attenuating hypertensive myocardial
fibrosis through, at least partly, suppression of TGF-β1/Smad signaling pathway.