title: Suppression of TGF-β1/Smad signaling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats.
abstract: 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.
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Mengqiu
authors: M
authors: Zhao
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Shuguo
authors: S
authors: Zheng
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Jieren
authors: J
authors: Yang
authors: Department of Basic Theory of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230038, China.
authors: Yuanjie
authors: Y
authors: Wu
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Younan
authors: Y
authors: Ren
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Xiang
authors: X
authors: Kong
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Wei
authors: W
authors: Li
authors: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.
authors: Jiali
authors: J
authors: Xuan
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019255:NADPH Oxidases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism*; D051906:Smad7 Protein / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D024061:Collagen Type III; D004149:Dioxoles; D017705:Lignans; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C054125:sesamin