Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica

Abstract

Context:The petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF). Objective: To evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses. Materials and methods: Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety. Results: The PET LD 50 was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect. Conclusions: These findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application.

Metabolomics reveal the mechanism for anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica

“…Recent studies showed that BUT of A. mongolica was effective in the prevention of RF (5,(13)(14)(15)(16). However, the optimal dose and the mechanisms underlying the antifibrotic effects of BUT are still unclear.…”

“…Biochemical assays were performed to assess the effect of drug treatment on the kidney functions of rats. For positive control, we chose benazepril, an angiotensin II inhibitor that reduces plasma aldosterone levels, increases vasodilatation, lowers blood pressure, relieves oxidative stress, increases glomerular filtration rate and reduces proteinuria (5). As shown in Fig.…”

“…Currently, very few therapeutics are available for effective RF treatment. Traditional Chinese medicine (TCM) formulations are promising alternatives for the prevention and treatment of RF (5). Exploring RF treatment with TCM is gaining attention in the medical community.…”

“…Yu Li Ren is a TCM used in the adjuvant treatment of nephropathy and glomerulonephritis (10,11). Recent reports have shown that A. mongolica contains amygdalin, alkaloids and other pharmacological components (5). Previous studies showed that the content of amygdalin in the n-butanol extract (BUT) of A. mongolica was 47.72 %.…”

“…A recent study showed that A. mongolica total extract (TOT) had the effect of antirenal fibrosis in rats (13). In addition, the petroleum ether and BUT of A. mongolica were the effective active sites to prevent pulmonary fibrosis and RF (5,(14)(15)(16). However, the mechanisms underlying the antifibrotic effects of A. mongolica BUT are still unclear.…”