Icariside II improves myocardial fibrosis in spontaneously hypertensive rats by inhibiting collagen synthesis

OBJECTIVES: We aimed to investigate the effects of icariside II (ICS II) on myocardial fibrosis in spontaneously hypertensive rats (SHRs) and to explore the possible mechanisms. METHODS: We used SHRs as animal models, and we administered ICS II (4, 8 or 16 mg/kg) orally by gavage for 12 consecutive weeks (Fu et al., Biomed Pharmacother 2018; 100: 64). The left ventricular morphology of the rats was observed using haematoxylin-eosin (HE) staining. The occurrence of myocardial interstitial fibrosis was detected by Masson's trichrome staining. The protein levels of alpha smooth muscle actin (α-SMA), Collagen I, III, matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively), tissue inhibitor of metalloproteinase 1 (TIMP-1), transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), phospho-Smad3 (p-Smad3) and phospho-p38 (p-p38) were examined by Western blotting. KEY FINDINGS: The results suggested that ICS II improved myocardial interstitial and perivascular collagen deposition and decreased Collagen I/III and α-SMA expression. ICS II (8 and 16 mg/kg) downregulated the expression of MMP-2 and MMP9 and upregulated the expression of TIMP1. In addition, the protein levels of p-Smad2/3, TGF-β1 and p-p38 were decreased by ICS II treatment. CONCLUSIONS: The results suggest that ICS II can inhibit the expression of Collagen I and Collagen III through the MMP/TIMP-1 and TGF-β1/Smad2,3/p-p38 signalling pathways and that it has therapeutic effects on myocardial fibrosis.