baohuoside-i and Hypertension

Reducing endoplasmic reticulum stress (ERS)-induced cardiomyocyte apoptosis is a key strategy for preventing hypertensive heart disease. In our previous study, Icariside II can improve left ventricular remodelling in spontaneously hypertensive rats (SHRs). This study aims to determine whether Icariside II can exert its effect by inhibiting ERS-induced cardiomyocyte apoptosis via the PERK/ATF-4/CHOP signalling pathway.. Spontaneously hypertensive rats were randomly divided into model group and Icariside II groups. The rats in the Icariside II groups were intragastrically administrated with Icariside II 4, 8 and 16 mg/kg from 14 to 26 week-age, respectively. The left ventricular function was measured at the 18, 22 and 26 week-age by small animal ultrasound. At the end of the 26th week, cardiomyocyte apoptosis was analysed and the levels of GRP78, PERK, ATF-4 and CHOP gene and protein were detected.. The function of left ventricular became declined with age in SHRs, but improved in Icariside II groups. Myocardial apoptosis was aggravated in SHRs, but alleviated in Icariside II groups. Icariside II could reduce the levels of GRP78, PERK, ATF-4, CHOP gene and protein that increased in SHRs.. Icariside II prevents hypertensive heart disease by alleviating ERS-induced cardiomyocyte apoptosis, and its mechanism is related to the impediment of the PERK/ATF-4/CHOP signalling pathway.

Topics: Activating Transcription Factor 4; Animals; eIF-2 Kinase; Endoplasmic Reticulum Stress; Flavonoids; Heart Diseases; Hypertension; Myocardium; Rats; Rats, Inbred SHR; Signal Transduction; Transcription Factor CHOP

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-β and the nuclear factor κB 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-1β (IL-1β), tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), Smad2, inhibitory κB (IκB), and nuclear factor κB (NF-κB) p65 by Western blot. The results showed that ICS II inhibited NF-κB p65 expression and the TGF-β1/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-kB signalling and the TGF-β1/Smad2 signalling pathway.

Topics: Animals; Blood Pressure; Drugs, Chinese Herbal; Fibrosis; Flavonoids; Hypertension; Male; Myocardium; NF-kappa B; Rats, Inbred SHR; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta1