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

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.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.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.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.