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

Abstract

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.

Keywords

• emodin
• microbiome
• hypertension