Coix lacryma-jobi peptide alleviated rat hypertension and hyperlipidemia based on the regulation of inflammatory reaction and lipid metabolism

The coincidence of hypertension and hyperlipidemia (HTN-HLP) is one major risk factor of cardiovascular disease with great morbidity and mortality. Seeds of Coix lacryma-jobi L. are commonly used to treat hypertension and hyperlipidemia in Traditional Chinese Medicine. In our previous research, a hexapeptide IALNRF was obtained from Coix . The goal of this research was to investigate the therapeutic efficacy of IALNRF on HTN-HLP and the underlying mechanism. Molecular docking revealed that IALNRF interacted with angiotensin-converting enzyme with IC 50 of 166.47 μmol/L. Then HTN-HLP rat model was generated by feeding high-fat diet. IALNRF treatment displayed significant decrease of blood pressure, prevention of the body weight gain, alleviation of hepatic fat accumulation and hemorheological indexes in rats. Echocardiography indicated significantly improved cardiac function. Serum biomarkers including angiotensin, Reactive oxygen species and NO have obviously improved. RNA-seq revealed 428 differentially expressed genes in kidney tissue that were primarily enriched in inflammatory and lipid metabolism pathways. The qRT-PCR confirmed the down-regulated expression of IL-6, IL-1β, and TNF-α in the kidney versus the up-regulated expression of PPARα and FABP1 in the liver. Immunohistochemistry analysis indicted that the expression of transcription factor c-Fos in the peptide treatment group was significantly decreased, and it was speculated that c-Fos maybe the key regulator for IALNRF alleviating HTN-HLP. • Obtained novel angiotensin-converting enzyme inhibitory peptide IALNRF from Coix. • Hypertension and hyperlipidemia (HTN-HLP) rat model was established. • IALNRF alleviated hypertension and liver lipid accumulation for HTN-HLP rats. • IALNRF improved blood rheology, serum biomarkers and cardiac function of the rats. • Differential expressed genes mainly related to inflammatory and lipid metabolism.