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

To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg-1) and BUT-treated (1.75, 1.5 and 1.25 g kg-1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

A metabolomic approach to elucidate the inhibitory effects of baicalin in pulmonary fibrosis.

CONTEXT: Baicalin, a major flavonoid extracted from Scutellaria baicalensis Georgi (Lamiaceae), has been shown to exert therapeutic effects on pulmonary fibrosis (PF). OBJECTIVE: To use serum metabolomics combined with biochemical and histopathological analyses to clarify anti-PF mechanisms of baicalin on metabolic pathways and the levels of potential biomarkers. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly divided into the control, PF model, prednisolone acetate-treated (4.2 mg/kg/day) and baicalin-treated (25 and 100 mg/kg/day) groups. A rat model of PF was established using a tracheal injection of bleomycin, and the respective drugs were administered intragastrically for 4 weeks. Histomorphology of lung tissue was examined after H&E and Masson's trichrome staining. Biochemical indicators including SOD, MDA and HYP were measured. Serum-metabonomic analysis based on UPLC-Q-TOF/MS was used to clarify the changes in potential biomarkers among different groups of PF rats. RESULTS: Both doses of baicalin effectively alleviated bleomycin-induced pathological changes, and increased the levels of SOD (from 69.48 to 99.50 and 112.30, respectively), reduced the levels of MDA (from 10.91 to 5.0 and 7.53, respectively) and HYP (from 0.63 to 0.41 and 0.49, respectively). Forty-eight potential biomarkers associated with PF were identified. Meanwhile, the metabolic profiles and fluctuating metabolite levels were normalized or partially reversed after baicalin treatment. Furthermore, baicalin was found to improve PF potentially by the regulation of four key biomarkers involving taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism. CONCLUSIONS: These findings revealed the anti-fibrotic mechanisms of baicalin and it may be considered as an effective therapy for PF.

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 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.

Protective effects of Amygdalus mongolica on rats with renal fibrosis based on serum metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Renal fibrosis (RF) is a common outcome of various progressive chronic kidney diseases (CKDs) and, thus, seriously endangers human health. As the active ingredient of Amygdalus mongolica, amygdalin inhibits RF. Furthermore, our previous studies demonstrated that n-butanol extract (BUT) and petroleum ether extract (PET), which are effective components of A. mongolica, have an anti-renal fibrosis effect. However, their potential mechanisms of action are unclear and need further verification. AIMS OF THE STUDY: The aims of this study were to further investigate the effects and potential mechanisms of A. mongolica extracts in the treatment of RF. MATERIALS AND METHODS: The animals were divided into the control group, RF model group, PET group and BUT group. The RF rat model was established through unilateral ureteral obstruction (UUO). Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), and hydroxyproline (HYP, a routine marker of fibrosis), and the antioxidant index (including superoxide dismutase (SOD) and malondialdehyde (MDA)) were measured to evaluate the anti-RF effects of the extracts of A. mongolica. The histomorphology of renal tissue was observed and scored by HE and Masson staining. A serum metabonomic analysis based on UPLC-Q-TOF/MS was performed to assess the changes in the metabolic profile among the different groups. RESULTS: The results showed that PET and BUT significantly improved tubulointerstitial damage and fibrosis by reducing the levels of Scr, BUN, HYP, and MDA and increasing the level of SOD. Moreover, no significant differences in efficacy were observed between the BUT and PET groups. According to the metabolomics analysis, seventy-four potential biomarkers were identified, and eight crucial biomarkers were further selected. These key biomarkers significantly contributed to RF progression by participating in six metabolic pathways, including pathways involved in arginine and proline metabolism, histidine metabolism, nicotinamide metabolism, pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and amino sugar and nucleotide sugar metabolism. In addition, eight key biomarkers and six crucial biomarkers were restored to levels similar to those observed in controls following the treatment with PET and BUT, respectively. CONCLUSIONS: The outcomes of these studies demonstrate the renoprotective effects of A. mongolica extracts in rats with RF and revealed the mechanism underlying these antifibrotic effects on metabolic activity for the first time.

[The analysis of the content of bile acids in ox-bile powder and goat gall powder of Mongolian medicine].

The present study was to detect and compare the content of bile acids in ox bile powder and goat gall powder of Mongolia medicine by UV. Cholic acid with sulphuric acid were heated and dehydrated, and they produced conjugated double bond. The conjugated bond showed the same absorption peak in the ultraviolet range. The method of ultraviolet spectrophotometry can be used to detect and compare the content of bile acids in ox bile powder and goat gall powder. The result showed that the linear range was 0.003 3-0.016 7 mg x mL(-1) (r = 0.999 7). The average recovery (n = 5) of standard addition method of ox bile powder and goat gall powder was 98.48% (RSD = 1.79%) and 96.46% (RSD = 2.50%) respectively. The result of determination of five different samples showed that the content of bile acids in ox bile powder and goat gall powder was 40.85%-43.03% and 30.88%-32.64% respectively. The RSD of the analysis of ox bile powder and goat ball powder was 2.40% and 2.92% respectively, the RSD of stationary test of ox bile powder and goat ball powder in eight hours was 0.55% and 0.59% respectively, and the RSD of reproducibility of the analysis of ox bile powder and goat ball powder was 2.11% and 2.68% respectively. The method was simple, accurate, fast and easy to generalize and apply in many fields. It can be used to control the quality of ox bile powder and goat gall powder.