Emodin Inhibited Pathological Cardiac Hypertrophy in Response to Angiotensin-Induced Hypertension and Altered the Gut Microbiome.

OBJECTIVE: Evidence suggests that food bioactives affect the epigenome to prevent pathological cardiac hypertrophy. Recently, we showed that emodin, an anthraquinone, attenuated pathological cardiac hypertrophy and histone deacetylase (HDAC) activity. However, we only examined the cardioprotective effects of emodin's parent compound and not those of emodin metabolites or of emodin-gut microbiome interactions. The microbiome has emerged as a key player in chronic diseases such as metabolic and cardiac disease. Thus, we hypothesized that emodin could reverse hypertension-induced changes in microbial communities. METHODS: Normo- and hypertensive (angiotensin II) C57/BL6 female mice were randomly assigned to receive a vehicle (Veh; DMSO:PEG 1:1) or emodin (Emod; 30 mg/kg) for 14 days. Body weights were collected pre- and post-treatment, and blood pressure was assessed via tail cuff. At the study's end, the mice were euthanized and assessed for their heart weights. In addition, stool samples and cecal contents were collected to elucidate changes in the microbial populations using 16S rRNA sequencing. Lastly, the tissue was lysed, and RNA was isolated for qPCR. One-way ANOVA with Tukey's post hoc test was performed unless otherwise specified, and p < 0.05 was considered significant. RESULTS: Emodin significantly attenuated cardiac hypertrophy in the female mice. No significant changes were observed in body weight or systolic blood pressure in response to hypertension or emodin. Lastly, analysis suggests that hypertension altered the microbiome in the cecum and cecal content, with additional evidence to support that emodin affects gut microbiota in the feces and colon. CONCLUSIONS: Our data demonstrate that emodin attenuates pathological hypertrophy in female mice. Future research is needed to dissect if changes in the microbiome contributes to emodin-mediated attenuation in cardiac remodeling.

Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy.

Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e., phytochemicals, are credited with protecting the heart. However, the mechanistic actions of phytochemicals, which prevent clinical endpoints, such as pathological cardiac hypertrophy, are still being elucidated. We sought to characterize the overlapping and divergent mechanisms by which 18 selected phytochemicals prevent phenylephrine- and phorbol 12-myristate 13-acetate-mediated cardiomyocyte enlargement. Of the tested 18 compounds, six attenuated PE- and PMA-mediated enlargement of neonatal rat ventricular myocytes. Cell viability assays showed that apigenin, baicalein, berberine hydrochloride, emodin, luteolin and quercetin dihydrate did not reduce cell size through cytotoxicity. Four of the six phytochemicals, apigenin, baicalein, berberine hydrochloride and emodin, robustly inhibited stress-induced hypertrophy and were analyzed further against intracellular signaling and genome-wide changes in mRNA expression. The four phytochemicals differentially regulated mitogen-activated protein kinases and protein kinase D. RNA-sequencing further showed divergence in gene regulation, while pathway analysis demonstrated overlap in the regulation of inflammatory pathways. Combined, this study provided a comprehensive analysis of cardioprotective phytochemicals. These data highlight two defining observations: (1) that these compounds predominantly target divergent gene pathways within cardiac myocytes and (2) that regulation of overlapping signaling and gene pathways may be of particular importance for the anti-hypertrophic actions of these phytochemicals. Despite these new findings, future works investigating rodent models of heart failure are still needed to understand the roles for these compounds in the heart.