Mechanisms of Chinese Medicine Xinmailong’s protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes

Abstract

Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML’s effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3β and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3β, subsequently inhibiting protein expression of GATA4 in nucleus (P < 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3β, and GATA4 signaling pathway.

Gentisic acid attenuates pressure overload‐induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway

“…This activation of ERK1/2 is consistent with reports showing that TAC triggers ERK1/2 phosphorylation. [36][37][38] The inhibitory effect of gentisic acid on ERK1/2 activation was almost the same as that noted following administration of bisoprolol or dilti- that employed in our animal experiments was very high (70 times greater), possibly explaining the stronger reduction in TAC-associated cardiac fibrosis noted using this drug. In contrast, the diltiazem dose used in our investigation was three times higher than that given to patients (90 mg twice daily).…”

“…However, p38 and JNK1/2 activation was not clearly observed in hearts following 5 weeks of TAC. This activation of ERK1/2 is consistent with reports showing that TAC triggers ERK1/2 phosphorylation . The inhibitory effect of gentisic acid on ERK1/2 activation was almost the same as that noted following administration of bisoprolol or diltiazem.…”

Periplaneta Americana Extract May Attenuate Renal Fibrosis through Inhibiting Janus Tyrosine Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway

“…Previous studies have demonstrated that PAE has many medicinal values and has been explored as an alternative remedy for many diseases, such as heart disease, cancer, burn wounds, gastric ulcer, and so on [2, 3]. Other researches have also found that PAE could suppress liver fibrosis [4].…”

“…Importantly, periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases, such as heart disease, cancer, burn wounds, gastric ulcer, and so on [1-3]. Interestingly, PAE also has the effect of anti-liver fibrosis.…”

Signature‐oriented investigation of the efficacy of multicomponent drugs against heart failure

“…Multicomponent drugs represented by traditional Chinese medicine (TCM) have drawn increasing attention in HF treatment (7)(8)(9)(10)(11)(12)(13). Potentially relevant TCM characteristics include its multiconstituent and multitarget features (12); in addition, TCM has fewer adverse effects in some cases than in controls or with Western medication in some studies (11).…”