Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload-induced heart failure mice.

Cardiac remodeling is a commonly observed pathophysiological phenomenon associated with the progression of heart failure in various cardiovascular disorders. Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti-inflammatory, antioxidant, and anti-apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC-induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II-induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti-inflammatory, anti-oxidative, and anti-apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1/PI3K/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti-inflammatory, anti-oxidative, and anti-apoptotic effects mediated by Sirt1/PI3K/AKT signaling pathways, thereby alleviating heart failure and VF.

Astilbin protects from sepsis-induced cardiac injury through the NRF2/HO-1 and TLR4/NF-κB pathway.

Cardiac dysfunction and arrhythmia are severe complications of sepsis-induced cardiomyopathy and are associated with an increased risk of morbidity and mortality. Currently, the precise mechanism for sepsis-induced myocardial damage remains unclear. Astilbin, a flavonoid, is reported to have anti-inflammatory, antioxidative, and antiapoptotic properties. However, the effects of astilbin on sepsis-induced cardiomyopathy have not been studied so far. This study aims to investigate the effect of astilbin in sepsis-induced myocardial injury and elucidate the underlying mechanism. In vivo and in vitro sepsis models were created using lipopolysaccharide (LPS) as an inducer in H9C2 cardiomyocytes and C57BL/6 mice, respectively. Our results demonstrated that astilbin reduced myocardial injury and improved cardiac function. Moreover, astilbin prolonged the QT and corrected QT intervals, attenuated myocardial electrical remodeling, and promoted gap junction protein (Cx43) and ion channels expression, thereby reducing the susceptibility of ventricular fibrillation. In addition, astilbin alleviated LPS-induced inflammation, oxidative stress, and apoptosis. Astilbin suppressed the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in vivo and in vitro models. Astilbin remarkedly upregulated the nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1) expression. The in vitro treatment with an NRF2 inhibitor reversed the inhibition of the TLR4/NF-κB pathway and antioxidant properties of astilbin. Astilbin attenuated LPS-induced myocardial injury, cardiac dysfunction, susceptibility to VF, inflammation, oxidative stress, and apoptosis by activating the NRF2/HO-1 pathway and inhibiting TLR4/ NF-κB pathway. These results suggest that astilbin could be an effective and promising therapeutics target for the treatment of sepsis-induced cardiomyopathy.

Germacrone mitigates cardiac remodeling by regulating PI3K/AKT-mediated oxidative stress, inflammation, and apoptosis.

Cardiac remodeling is a common consequence of cardiovascular diseases and is closely associated with oxidative stress, inflammation, and apoptosis. Germacrone, a bioactive compound present in Rhizoma curcuma, has been shown to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the protective effect of germacrone against cardiac remodeling. Here, C57BL/6 mice were subcutaneous injection with isoproterenol (ISO) once daily for two weeks and were concurrent intragastric injection of germacrone. In vitro, neonatal rat cardiomyocytes (NRCMs) were used to verify the protective effect of germacrone on ISO-induced cardiac injury. Our findings indicated that ISO induce oxidative stress, inflammation, and apoptosis in vivo and in vitro, while germacrone treatment significantly attenuates these effects, thereby attenuating myocardium remodeling and cardiac dysfunction. Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling.

Curcumol alleviates cardiac remodeling via the AKT/NF-κB pathway.

Cardiac remodeling is the final stage of almost all cardiovascular diseases, leading to heart failure and arrhythmias. However, the pathogenesis of cardiac remodeling is not fully understood, and specific treatment schemes are currently unavailable. Curcumol is a bioactive sesquiterpenoid that has anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. This study aimed to investigate the protective effect of curcumol on cardiac remodeling and elucidate its relevant underlying mechanism. Curcumol significantly attenuated cardiac dysfunction, myocardial fibrosis, and hypertrophy in the animal model of isoproterenol (ISO)-induced cardiac remodeling. Curcumol also alleviated cardiac electrical remodeling, thereby reducing the risk of ventricular fibrillation (VF) after heart failure. Inflammation and apoptosis are critical pathological processes involved in cardiac remodeling. Curcumol inhibited the inflammation and apoptosis induced by ISO and TGF-ß1 in mouse myocardium and neonatal rat cardiomyocytes (NRCMs). Furthermore, the protective effects of curcumol were found to be mediated through the inhibition of the protein kinase B (AKT)/nuclear factor-kappa B (NF-κB) pathway. The administration of an AKT agonist reversed the anti-fibrotic, anti-inflammatory, and anti-apoptotic effects of curcumol and restored the inhibition of NF-κB nuclear translocation in TGF-ß1-induced NRCMs. Our study suggests that curcumol is a potential therapeutic agent for the treatment of cardiac remodeling.

Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge.

Previous studies suggest that autonomic dysfunction is associated with disease severity in acute phase in patients with coronavirus disease 2019 (COVID-19). However, the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 is unknown. We conducted a prospective study to investigate the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 discharged for 6 months. We included 40 eligible participants and collected the following indicators: heart rate variability (HRV), pulmonary function tests (PFTs), lung X-ray computed tomography (CT), routine blood parameters, liver function parameters, and lymphocyte subsets. We found that at 6 months post-discharge, HRV still had a tight correlation with pulmonary fibrosis. There was a significant difference in HRV between patients with and without diffusion dysfunction, but HRV did not differ between patients with or without ventilatory dysfunction. Diffusion dysfunction and pulmonary fibrosis were tightly associated, and HRV index changes in patients with diffusion dysfunction had the same trend as that of patients with pulmonary fibrosis. They had a lower standard deviation of NN intervals (SDNN), the standard deviation of the average NN intervals (SDANN), and the triangular index, but a higher ratio between LF and HF power (LF/HF). In addition, WBC, neutrophils, and CD4/CD8 were correlated with pulmonary fibrosis and HRV. We concluded that autonomic dysfunction is closely associated with pulmonary fibrosis and diffusion dysfunction, and immune mechanisms may potentially contribute to this process.