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Suppression of TGF-β1/Smad signaling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats.

Zhao M, Zheng S, Yang J, Wu Y, Ren Y, Kong X, Li W, Xuan J - PLoS ONE (2015)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of sesamin on protein expression of SOD and p47phox.After supplementation with sesamin or captopril for 12 weeks, total protein were extracted from left ventricular tissues and subjected to western blot analysis as detailed in the Methods section. Levels of SOD and p47phox protein were normalized to that of tubulin. Data were presented as percentage of that in WKY rats (mean±SD, n = 4). a P <0.05, b P <0.01 vs. WKY group; c P <0.05, d P <0.01 vs. SHR group.
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pone.0121312.g007: Effect of sesamin on protein expression of SOD and p47phox.After supplementation with sesamin or captopril for 12 weeks, total protein were extracted from left ventricular tissues and subjected to western blot analysis as detailed in the Methods section. Levels of SOD and p47phox protein were normalized to that of tubulin. Data were presented as percentage of that in WKY rats (mean±SD, n = 4). a P <0.05, b P <0.01 vs. WKY group; c P <0.05, d P <0.01 vs. SHR group.

Mentions: As shown in Fig. 7, left ventricular level of SOD protein in SHR group was significantly decreased as compared to that in WKY group (56.8% ± 7.1% vs 100%, P <0.01), while the level of p47phox was increased markedly (188.1% ± 15.2% vs 100%, P <0.01). Supplementation with sesamin resulted in a significant up-regulation of SOD protein (76.5% ± 9.0%, 88.2% ± 6.3%, P <0.05 or P <0.01) and down-regulation of p47phox protein (155.0% ± 13.7%, 122.7% ± 13.6%, P <0.05 or P <0.01). Treatment with captopril also effectively increased SOD protein expression (83.4% ± 7.0%, P <0.01) and decreased p47phox protein expression (144.4% ± 16.3%, P <0.05). Both captopril and sesamin can only promote partial reversion of SOD and p47phox protein in SHRs as compared to those in WKY rats (P <0.05 or P <0.01).


Suppression of TGF-β1/Smad signaling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats.

Zhao M, Zheng S, Yang J, Wu Y, Ren Y, Kong X, Li W, Xuan J - PLoS ONE (2015)

Effect of sesamin on protein expression of SOD and p47phox.After supplementation with sesamin or captopril for 12 weeks, total protein were extracted from left ventricular tissues and subjected to western blot analysis as detailed in the Methods section. Levels of SOD and p47phox protein were normalized to that of tubulin. Data were presented as percentage of that in WKY rats (mean±SD, n = 4). a P <0.05, b P <0.01 vs. WKY group; c P <0.05, d P <0.01 vs. SHR group.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4368740&req=5

pone.0121312.g007: Effect of sesamin on protein expression of SOD and p47phox.After supplementation with sesamin or captopril for 12 weeks, total protein were extracted from left ventricular tissues and subjected to western blot analysis as detailed in the Methods section. Levels of SOD and p47phox protein were normalized to that of tubulin. Data were presented as percentage of that in WKY rats (mean±SD, n = 4). a P <0.05, b P <0.01 vs. WKY group; c P <0.05, d P <0.01 vs. SHR group.
Mentions: As shown in Fig. 7, left ventricular level of SOD protein in SHR group was significantly decreased as compared to that in WKY group (56.8% ± 7.1% vs 100%, P <0.01), while the level of p47phox was increased markedly (188.1% ± 15.2% vs 100%, P <0.01). Supplementation with sesamin resulted in a significant up-regulation of SOD protein (76.5% ± 9.0%, 88.2% ± 6.3%, P <0.05 or P <0.01) and down-regulation of p47phox protein (155.0% ± 13.7%, 122.7% ± 13.6%, P <0.05 or P <0.01). Treatment with captopril also effectively increased SOD protein expression (83.4% ± 7.0%, P <0.01) and decreased p47phox protein expression (144.4% ± 16.3%, P <0.05). Both captopril and sesamin can only promote partial reversion of SOD and p47phox protein in SHRs as compared to those in WKY rats (P <0.05 or P <0.01).

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China.

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.

No MeSH data available.


Related in: MedlinePlus