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

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 a...

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Main Authors: Chen Gao, Wan-fu Bai, Hong-bing Zhou, Hai-mei Hao, Ying-chun Bai, Quan-li Liu, Hong Chang, Song-li Shi
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Pharmaceutical Biology
Subjects:
Online Access:http://dx.doi.org/10.1080/13880209.2021.1920619
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author Chen Gao
Wan-fu Bai
Hong-bing Zhou
Hai-mei Hao
Ying-chun Bai
Quan-li Liu
Hong Chang
Song-li Shi
author_facet Chen Gao
Wan-fu Bai
Hong-bing Zhou
Hai-mei Hao
Ying-chun Bai
Quan-li Liu
Hong Chang
Song-li Shi
author_sort Chen Gao
collection DOAJ
description 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 LD50 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.
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spelling doaj.art-db63d466de4b4b5ca8423ab56bb2499d2022-12-21T22:55:12ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162021-01-0159156557410.1080/13880209.2021.19206191920619Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolicaChen Gao0Wan-fu Bai1Hong-bing Zhou2Hai-mei Hao3Ying-chun Bai4Quan-li Liu5Hong Chang6Song-li Shi7Department of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and TechnologyContext 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 LD50 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.http://dx.doi.org/10.1080/13880209.2021.1920619traditional chinese medicinerenal fibrosisbiomarkersmetabolic pathwaymechanism research
spellingShingle Chen Gao
Wan-fu Bai
Hong-bing Zhou
Hai-mei Hao
Ying-chun Bai
Quan-li Liu
Hong Chang
Song-li Shi
Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
Pharmaceutical Biology
traditional chinese medicine
renal fibrosis
biomarkers
metabolic pathway
mechanism research
title Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
title_full Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
title_fullStr Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
title_full_unstemmed Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
title_short Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica
title_sort metabolomic assessment of mechanisms underlying anti renal fibrosis properties of petroleum ether extract from amygdalus mongolica
topic traditional chinese medicine
renal fibrosis
biomarkers
metabolic pathway
mechanism research
url http://dx.doi.org/10.1080/13880209.2021.1920619
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