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. 2022 Dec 8;8(12):e12126.
doi: 10.1016/j.heliyon.2022.e12126. eCollection 2022 Dec.

An integrative exploration of loquat leaf total sesquiterpene glycosides in treating insulin-resistant mice by serum and urine untargeted metabolomics analysis

Yanan Gai  1 , Jiawei Li  1 , Tunyu Jian  1 , Xiaoqin Ding  1 , Han Lyu  1 , Yan Liu  1 , Jing Li  2 , Bingru Ren  1 , Jian Chen  1   2 , Weilin Li  1   2
Affiliations

An integrative exploration of loquat leaf total sesquiterpene glycosides in treating insulin-resistant mice by serum and urine untargeted metabolomics analysis

Yanan Gai et al. Heliyon. .

Abstract

Loquat leaf is approved to be beneficial in the treatment of diabetes. Total sesquiterpene glycosides (TSG), a major chemical component cluster, has potential ability to improve insulin-resistant diabetes syndrome. Its therapeutic mechanism using metabolomics in vivo is worth to be investigated. This study aimed to reveal the underlying therapeutic mechanism of TSG on insulin-resistant mice by untargeted metabolomics, and to explore the lipid metabolism differences in vivo. High-fat diet was used to induce insulin-resistant mice model. Biochemical indicators were applied to evaluate the model validity and related treatment effect. Ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry was utilized to accomplish serum and urine untargeted metabolomics. Oral administration of TSG had a therapeutic effect on high-fat diet induced insulin-resistant mice. Four hundred forty-two metabolites in serum and 1732 metabolites in urine were annotated. Principal component analysis screened 324 differential metabolic signatures in serum sample and 1408 in urine sample. The pathway mainly involved purine metabolism and biosynthesis of unsaturated fatty acids. Lipidomic analysis of urine and serum confirmed that most lipid metabolites were fatty acyls, sterol lipids and polyketides.

Keywords: Insulin resistance; Lipid metabolism; Loquat leaf; Metabolic pathway; Total sesquiterpene glycosides; Untargeted metabolomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Image 1
Graphical abstract
Figure 1
Figure 1
Chemical structures of chain sesquiterpene glycosides, single cyclic sesquiterpene glycosides, and ionone sesquiterpene glycosides.
Figure 2
Figure 2
Effects of TSG on diets induced IR mice (A) Body weight of IR mice during 18 weeks. Control (n = 10 mice), Model (n = 10 mice), TSH (100 mg/kg, n = 9 mice) and TSL (25 mg/kg, n = 19 mice). Quantitation of (B) TC, (C) TG, (D) LDL-C and (E) HDL-C. Quantitation of (F) blood glucose, (G) OGTT, (H) blood insulin, and (I) ITT. All data were presented as mean ± SEM. ##P < 0.01, ###P < 0.001, significant difference compared with Control group. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, significant difference compared with Model group. Statistical differences between group means were determined by one-way ANOVA.
Figure 3
Figure 3
Volcanic plot of differential (A) serum and (B) urine metabolites with the comparison of model groups. Venn diagram of differential (C) serum and (D) urine metabolites.
Figure 4
Figure 4
Pathways with most regulated metabolites annotated in serum and urine separately (A) Purine metabolism (B) Biosynthesis of unsaturated fatty acids.
Figure 5
Figure 5
Function of lipid metabolites in (A) serum and (B) urine after TSG treatment detected in positive mode (the upper diagram) and negative mode (the lower diagram).
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