Identification of Antihypertensive Mechanisms ofFicus deltoidea kunstleri; in Spontaneously Hypertensive Rats Using Metabolomics

Abstract

Blood pressure lowering effect of Ficus deltoidea kunstleri (FDK) has been associated with changes in the Renin-Angiotensin-Aldosterone System (RAAS) and endothelial function in Spontaneously Hypertensive Rats (SHR). Whether it also involves other systems is unclear. This study therefore screened for other potential BP lowering mechanisms in FDK-treated SHR based on urine metabolite profile obtained using 1H-NMR spectrometry and multivariate data analysis. Male SHR were administered orally, either 0.5 mL of distilled water (control), or 1000 mg.kg-1 body weight of FDK or 10 mg.kg-1 body weight of losartan once daily for 4 weeks. BP was measured weekly and 24-hr urine was collected using metabolic chambers at the end of the 4th week. Animals were then euthanised and blood was collected for estimation of total anti-oxidant capacity TAC. Kidneys were harvested for antioxidant enzyme gene expression studies. BP in FDK- and losartan-treated SHR was significantly lower, whereas serum TAC was significantly higher than those in the controls. Orthogonal partial least square analysis indicated that FDK-treated SHR were separated from controls by the presence of a larger number of ketone body and amino acid metabolism intermediates. Superoxide dismutase-2, catalase and fork head box gene expressions were higher in kidneys of FDK-treated SHR than those in the controls. It appears that apart from RAAS, the BP lowering effect of standardized aqueous-ethanolic extract of leaves of FDK in SHR is also associated with increased TAC, antioxidant enzyme expressions and probably also involves multiple metabolic pathways, including those involving ketone bodies, amino acids and energy metabolism