Platycodin D Reverses Pathological Cardiac Hypertrophy and Fibrosis in Spontaneously Hypertensive Rats

Abstract

Platycodin D (PD) is the main active saponin isolated from Platycodon grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti-inflammation and anti-obesity biological effects. The current study aims to evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling pathway. Significant increases in the cardiac functional indices of left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric hypertrophy markers, such as CaMKII[Formula: see text] and calcineurin; and expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously hypertensive groups. PD treatment reversed these increases in SHRs. In addition, an increase in the fibrosis markers FGF2, uPA, MMP2, MMP9, TGF[Formula: see text]-1 and CTGF during cardiac hypertrophy was detected by western blotting analyses. These results demonstrated that PD treatment considerably attenuates cardiac fibrosis. Histopathological examination revealed that PD treatment remarkably reduced collagen accumulation in contrast to spontaneously hypertensive groups. This study clearly suggests that PD provides myocardial protection by alleviating two damaging responses to hypertension, fibrosis and hypertrophy, in the heart.

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

“…DC., of the Campanulaceae family, which has traditionally been used to treat a variety of diseases in Korea, China, and Japan (Zhang et al 2015;Ji et al 2020). Recently, platycodin D has been shown to have multiple pharmacological properties, including anti-inflammatory (Fu et al 2018b;Ye et al 2019), immunostimulatory (Xie et al 2008), anti-cancer (Seo et al 2018;Huang et al 2019), antioxidant (Cho et al 2018;Wang et al 2018;Shi et al 2020), and inhibitory effects against various cardiovascular and metabolic diseases (Lin et al 2018;Liu et al 2020). The antioxidant activity of platycodin D has been primarily attributed to increased ROS scavenging activity and involves the activation of oxidative stress defense systems.…”

Eriobotrya japonica ameliorates cardiac hypertrophy in H9c2 cardiomyoblast and in spontaneously hypertensive rats

“…Studies from Molkentin et al, have explicitly demonstrated that pharmacological inhibition of this hypertrophic signaling pathway plays important for suppression of cardiac hypertrophy and heart failure . Additionally, recent report from our group has highlighted the attenuation of these signaling mediators for suppression of Ang‐II induced cardiac hypertrophy …”

Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts

“…Investigation of methods of interfering with fi broblast activation may thus provide novel therapeutic strategies for the treatment of pulmonary fi brosis. Reports have demonstrated previously that PD reverses pathological myocardial hypertrophy and fi brosis in spontaneous hypertension rats (16). Additionally, PD improves liver fi brosis and activates hepatic stellate cells by regulating JNK/c-JUN signal pathway (17).…”

“…To date, PD has received extensive attention due to its reported anti-infl ammatory, antiviral, antifi brosis and anti-cancer roles (12)(13)(14)(15). It has been well reported that PD reverses pathological myocardial hypertrophy and fi brosis in spontaneous hypertension rats (16). A study mentioned that by regulating JNK/c-JUN signal pathway, PD improves liver fi brosis and activates hepatic stellate cells (17).…”