Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.
BackgroundIn the Chinese traditional medicine, plant of Agastache rugosa (Fisch. & C.A. Mey.) Kuntze (A. rugosa) has been used to treat nausea, vomiting and dispel damp. However, currently, few reports about the chemical constituents, especially the non-volatile components of A. rugosa are available.MethodsThrough separation with various column chromatographies to elucidate the chemical constituents of A. rugosa, the biological activities of the major constituents were investigated. The extracts and main constituents of A. rugosa were evaluated for their anticoagulant effects by assaying the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) in vitro.ResultsSeven known compounds (namely compounds 1–7) were isolated from the aerial parts of A. rugosa. They were identified as methyl hexadecanoate (1), β-sitosterol (2), acacetin (3), ursolic acid (4), apigenin (5), protocatechuic acid (6) and tilianin (7), respectively. Compounds 1 and 6 were isolated from the genus Agastache for the first time, and compound 4 was obtained from the plants for the first time. The results showed that the extract of A. rugosa had a significant procoagulant activity by shortening the time of PT (P < 0.001) and increasing FIB content (P < 0.001), as compared with Vitamin K1. While its major constituents acacetin and tilianin exhibited significant anticoagulant activities by prolonging the times of PT, APTT, TT and reducing FIB content (P < 0.001), as compared with blank control group.ConclusionsThe total extract of A. rugosa possessed significant procoagulant activity, while its main components, acacetin and tilianin possessed significant anticoagulant activities. Further investigation should be pursued to find out the bioactivity components responsible for the procoagulant action of the plant.
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