Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 μM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.

Myocardial hypertrophy is an independent risk factor of cardiovascular diseases and is closely associated with the incidence of heart failure. In the present study, we hypothesized that difluoromethylornithine (DFMO) could attenuate cardiac hypertrophy through mitochondria‑associated membranes (MAM) and autophagy. Cardiac hypertrophy was induced in male rats by intravenous administration of isoproterenol (ISO; 5 mg/kg/day) for 1, 3,7 and 14 days. For DFMO treatment group, rats were given ISO (5 mg/kg/day) for 14 days and 2% DFMO in their water for 4 weeks. The expression of atrial natriuretic peptide (ANP) mRNA,heart parameters, apoptosis rate, fibrotic area and protein expressions of cleaved caspase3/9, GRP75, Mfn2, CypD and VDAC1 were measured to confirm the development of cardiac hypertrophy, apoptosis and autophagy induced by ISO. ANP mRNA and MAM protein expression levels were assessed by reverse transcription‑quantitative PCR and western blotting to evaluate hypertrophy and the effects of DFMO oral administration. The results demonstrated that heart parameters, ANP mRNA levels, fibrotic area and apoptosis rate were significantly increased in the heart tissue for ISO 7 and 14 day groups compared with the control group. Furthermore, treatment with DFMO significantly inhibited these indicators, and DFMO downregulated the MAM signaling pathway and upregulated the autophagy pathway in heart tissue compared with the ISO 14 day group. Overall, all ISO‑induced changes analyzed in the present study were attenuated following treatment with DFMO. The findings form this study suggested that DFMO treatment may be considered as a potential strategy for preventing ISO‑induced cardiac hypertrophy.

Background. It is well‐known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose‐ (HG‐, 30 mM) treated VSMCs in vitro. Methods. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR‐182‐5p, and tribble 3 (TRIB3). Then, dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR‐182‐5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results. In HG‐induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR‐182‐5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR‐182‐5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR‐182‐5p, by directly sponging miR‐182‐5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR‐182‐5p inhibition. Conclusion. This study reveals that hsa_circRNA_0008028 can act as a sponge of miR‐182‐5p and promote HG‐induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.

Resveratrol (Res) serves a protective role in hepatic, cardiovascular and autoimmune hypertrophic disease. However, the mechanisms by which Res ameliorates cardiac hypertrophy have not yet been fully elucidated. In the present study, network pharmacology was used to construct a network and perform enrichment analysis to evaluate the effect of Res on cardiac hypertrophy. Experimental validation was performed using 40 Sprague‑Dawley rats administered intragastric 80 mg/kg/day Res and 20 mg/kg/day 3‑methyladenine (3‑MA) for 4 weeks. A total of 444 targets associated with cardiac hypertrophy and 229 potential disease‑associated targets of Res were identified, from which 8 overlapping genes were demonstrated. Gene Ontology function and ‘Kyoto Encyclopedia of Genes and Genomes’ pathway enrichment analysis demonstrated that Res affected STAT3 and was associated with autophagy signaling pathways, including ‘negative regulation of autophagy for hypertrophic cardiomyopathy’. Furthermore, Res ameliorated isoprenaline‑induced cardiac hypertrophy, significantly improving cardiac dysfunction in vivo experiment (echocardiography, the degree of ventricular hypertrophy, etc.); this effect may be associated with regulation of autophagy and apoptosis. The autophagy inhibitor 3‑MA markedly reversed the anti‑cardiac hypertrophy effects of Res. In conclusion, Res inhibited cardiac hypertrophy via downregulation of the apoptosis signaling pathway and upregulating the autophagy pathway.

Traditional Chinese Medicine (TCM) formulations serve as a multi-component pharmacological combination therapy with various potential targets and have collected extensive knowledge regarding the in vivo efficacy of treating cardiovascular disorders in clinical practice for thousands of years. However, the obscurity of the chemicals and the molecular mechanisms are impediments to their continued growth and globalization. Therefore, new modern medications based on the combination of beneficial TCM components with precise clinical efficacy are required. The goal of this study was to find the best combination of Achyranthes bidentata Blume (AB) and Paeonia lactiflora Pall. (PL) for hypertension with liver yang hyperactivity (HLYH). The integrated research consisting of principal component analysis (PCA), metabolomics, microbiology, and weighted correlation network analysis (WGCNA) were used to find the optimal combination of AB-PL combinations and reveal the mechanism of action. The result showed AB-PL (2:3) had a substantial protective impact on HLYH, as shown by lower blood pressure, improved liver yang hyperactivity, reduced cardiac remodeling and malondialdehyde (MDA), and increased NO content. Furthermore, the essential elements for AB-PL reducing hypertension may be related to 135 metabolites and 23 microorganisms. In conclusion, our findings support the efficacy of herbal remedies in the treatment of hypertension and provide some pharmacological evidence for the ongoing development of novel modern Chinese drugs for cardiovascular disorders.