Breviscapine protects against cardiac hypertrophy through blocking PKC‐α‐dependent signaling

Abstract

Breviscapine is a mixture of flavonoid glycosides extracted from the Chinese herbs. Previous studies have shown that breviscapine possesses comprehensive pharmacological functions. However, very little is known about whether breviscapine have protective role on cardiac hypertrophy. The aim of the present study was to determine whether breviscapine attenuates cardiac hypertrophy induced by angiotensin II (Ang II) in cultured neonatal rat cardiac myocytes in vitro and pressure-overload-induced cardiac hypertrophy in mice in vivo. Our data demonstrated that breviscapine (2.5-15 microM) dose-dependently blocked cardiac hypertrophy induced by Ang II (1 microM) in vitro. The results further revealed that breviscapine (50 mg/kg/day) prevented cardiac hypertrophy induced by aortic banding as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. The inhibitory effect of breviscapine on cardiac hypertrophy is mediated by disrupting PKC-alpha-dependent ERK1/2 and PI3K/AKT signaling. Further studies showed that breviscapine inhibited inflammation by blocking NF-kappaB signaling, and attenuated fibrosis and collagen synthesis through abrogating Smad2/3 signaling. Therefore, these findings indicate that breviscapine, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis through suppression of PKC-alpha-dependent signaling.

Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway

“…Previous studies have demonstrated that breviscapine ameliorated cardiac hypertrophy that was induced by high glucose or angiotensin II. Studies have also reported that breviscapine had a protective effect against diabetic cardiomyopathy in diabetic rats [15][16][17] . However, little is known about whether breviscapine has a protective role in diabetic atherosclerosis, which is a common complication of diabetes mellitus that is independent of diabetic cardiomyopathy.…”

“…A number of reports have demonstrated that breviscapine possessed a strong inhibitory effect on PKC-α and PKC-β2 activation that contributed to its protective roles in cerebral ischemia, hepatic injury during brain death and cardiac hypertrophy [13,[15][16][17]33] . To investigate whether the protective effect of breviscapine on VSMCs is related to PKC, PKC-β2 activation was evaluated in VSMCs.…”

“…Breviscapine has been demonstrated to inhibit PKC and provide a protective effect against diabetic nephropathy in recent years [12][13][14] . Furthermore, it has been shown that the inhibitory effect of breviscapine on cardiac hypertrophy was mediated by disrupting PKC-α-dependent ERK1/2 and PI3K/AKT signaling [15] . Our previous studies have also indicated that breviscapine ameliorated the cardiac hypertrophy that was induced by high glucose in diabetic rats through inhibiting the PKC signaling pathway [16,17] .…”

Naringenin attenuates pressure overload-induced cardiac hypertrophy

“…Subsequently, the C57BL/6 mice were allocated at random into four groups: Sham + naringenin, AB + naringenin, sham + vehicle and AB + vehicle (n=15 per group). AB was performed as described previously (11). At 8 weeks after surgery, the animals were euthanized by cervical dislocation while anesthetized with 1.5% isoflurane, and the hearts were dissected and weighed to calculate the heart weight/body weight (HW/BW, in mg/g), heart weight/tibia length (HW/TL, in mg/mm) and lung weight/body weight (LW/BW, in mg/g) ratios in the naringenin-treated and vehicle-treated mice.…”

In Vivo and In Vitro Protective Effects of Pentamethylquercetin on Cardiac Hypertrophy

“…Then, hearts were cut transversely [20,21]. Sections were examined by light microscopy for lesions and changes in myofiber thickness or arrangement (H&E, ×200) and the myocyte cross sectional area was quantitatively analyzed with NIH Image 1.61 software as previously described (H&E, ×400) [6,18].…”