LC-MS/MS metabolomics approach for chemical characterization of Beta vulgaris subspecies maritima extract through untargeted molecular networking, in correlation to its renoprotective activity in renal ischemia/reperfusion induced injury model in rats

This study evaluates the reno-protective effect of Beta vulgaris subspecies maritima lyophilized 70% ethanolic extract (BVLE) in renal ischemia/reperfusion (I/R) induced injury model in rats. Detailed investigation of the effects of its oral administration was checked. serum blood urea nitrogen (BUN), which was reduced to 0.7 ± 0.04 mmol/L at a dose of 200 mg/Kg of BVLE compared to 1.9 ± 0.08 mmol/L for the I/R group. And creatinine levels were reduced to 1.2 ± 0.06 nmol/L at a dose of 200 mg/Kg of BVLE compared to 4.7 ± 0.12 nmol/L for the I/R group. Oxidative stress biomarkers including MDA (reduced to 0.4 ± 0.03 compared to 1.7 ± 0.05 nmol/mg protein of I/R a dose of 200 mg/Kg) and GSH levels (increased to 1.3 ± 0.03 compared to 0.3 ± 0.02 nmol/mg protein of I/R a dose of 200 mg/Kg). Meanwhile, inflammatory mediators including TNF-α and IL-6 levels were lowered to 46.7 ± 0.60 and 32.1 ± 1.78 pg/mg protein, respectively. Oxidative stress genetic pathways including Nrf2/HO-1 signaling pathway via testing Nrf2 and its dependent HO-1 mRNA expression levels were studied as well. Metabolomic profiling of BVLE was achieved by UPLC-HR-ESIMS coupled with molecular networking. BVLE significantly improved renal inflammatory markers, oxidative stress biomarkers and renal functions test, in dose dependent manner. Thirty-nine compounds were tentatively identified in BVLE by UPLC-MS/MS. Mainly flavonoid glycosides, triterpenoidal saponins and fatty acids. Among identified saponins five unreported betavulgaroside derivatives were tentatively described for the first time.