Icariside II attenuates myocardial fibrosis by inhibiting nuclear factor-kB and the TGF-β1/Smad2 signalling pathway in spontaneously hypertensive rats

Studies have demonstrated that icariin plays important roles in preventing hypertension and improving myocardial hypertrophy, inflammatory and infiltration. Icariside (ICS II) is the main metabolite of icariin, which has anti-inflammatory and anti-oxidant activities and protects against ischaemic brain injury. Whether ICS II improves myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the related mechanism remain unknown. Some studies have suggested that TGF-beta and the nuclear factor kappa B signalling pathway play a key role in the progression of myocardial fibrosis. Therefore, in the current study, we aimed to evaluate the effects of ICS II on induced myocardial fibrosis in SHRs and explore the mechanism underlying this activity. The SHRs were treated with ICS II (4, 8, and 16 mg/kg) via daily gavage for 12 weeks. Left ventricular function was detected using the Vevo2100 system, and the collagen area was measured by Masson staining. The results indicated that ICS II markedly improved left ventricular function and decreased the left ventricular myocardial collagen area compared with the SHR group. To further investigate the mechanism underlying this activity, we measured the protein expression of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta 1), Smad2, inhibitory kappa B (I kappa B), and nuclear factor kappa B (NF-kappa B) p65 by Western blot. The results showed that ICS II inhibited NF-kappa B p65 expression and the TGF-beta 1/Smad2 signalling pathways. In conclusion, the present results suggest that ICS II suppresses myocardial fibrosis in SHRs, and this effect might be at least partially mediated through suppression of NF-kappa B signalling and the TGF-beta 1/Smad2 signalling pathway.