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The protective effects of Berberine and Hesperidin on inflammatory factor-stimulating cardiac fibroblasts.

Abstract：

OBJECTIVE:The previous work has shown that Berberine and Hesperidin have beneficial effects on cardiovascular diseases. However, the underlying mechanisms remain unknown. This study aimed to investigate the effect of Berberine and Hesperidin on inflammatory cytokine secretion, proliferation, differentiation, and collagen synthesis of cardiac fibroblasts stimulated by the transforming growth factor-β1 (TGF-β1), and the potential of these drugs to regulate the Notch1 signaling pathway. PATIENTS AND METHODS:Neonatal rat primary cardiac fibroblasts were stimulated with 5 ng/mL TGF-β1 as model (TGF) group. In the Berberine (TGF+B) group cells were given TGF-β1, along with 1.25/2.5/5/10 mg/L Berberine, while the Hesperidin (TGF+H) group was treated with TGF-β1 and 12.5/25/50/100 µmmol/L Hesperidin. Cellular proliferation, differentiation, and collagen synthesis were evaluated. The role of the Notch1 signaling pathway in the protective effects of Berberine and Hesperidin was analyzed by using γ-secretase inhibitor (DAPT) to block the Notch1 pathway. RESULTS:5/10 mg/L Berberine intervention could noticeably decrease both TGF-β1 and IL-1β levels, 25/50/100 µmol/L Hesperidin could reduce IL-1β secretion from TGF-β1 stimulated cardiac fibroblasts. Both Berberine and Hesperidin decreased the expression of α-SMA and cell viability in a concentration-dependent manner; however, the apoptosis of cardiac fibroblasts was not influenced. 10 mg/L Berberine or at least 50 µmol/L Hesperidin could noticeably decrease MMP-1 expression, and at least 5 mg/L Berberine or 100 µmol/L Hesperidin could markedly reduce MMP-9 expression. Using DAPT to block Notch1 signaling could reverse the protective effects of Berberine and Hesperidin. CONCLUSIONS:Berberine and Hesperidin can reduce the secretion of inflammatory cytokines, differentiation, and proliferation, and increase the collagen synthesis of cardiac fibroblasts stimulated by TGF-β1 via the Notch1 signaling pathway.

journal_name

Eur Rev Med Pharmacol Sci

journal_title

European review for medical and pharmacological sciences

authors

Yu XH,Wang YF,Dai FY,Zhao JH,Li P

doi

10.26355/eurrev_201906_18216

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

5468-5476

issue

12

eissn

1128-3602

issn

2284-0729

journal_volume

23

pub_type

杂志文章

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