Study on the mechanism of acteoside in the treatment of pediatric chronic glomerulonephritis based on non-targeted metabolomics and lipidomics techniques

This study investigated the effects of acteoside (ACT) on serum metabolites in purinomycin aminonucleoside (PAN)-induced chronic glomerulonephritis (CGN) in young rats using non-targeted metabolomics and lipidomics, and initially explored its potential mechanism of efficacy. The experiment was approved by the Animal Welfare Ethics Committee of Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2022B152). Firstly, ELISA kits were used to detect serum cytokines including IP-10, IL-6, IL-1β, and TNF-α in rats of each group to evaluate the efficacy of ACT. Non-targeted metabolomics and lipidomics techniques were used to determine metabolites and lipids in serum, and integrated analysis was conducted to reveal the mechanism. The results showed that compared with the model group, the levels of IP-10, IL-6, IL-1β, and TNF-α in the serum of the ACT groups were significantly reduced, indicating a significant pharmacological effect of ACT. Non-targeted metabolomics results revealed that 23 different metabolites were identified between the control and model groups, involving pathways such as biosynthesis of unsaturated fatty acids, biosynthesis and degradation of valine, leucine, and isoleucine, and linoleic acid metabolism. Between the ACT and model groups, 25 different metabolites were identified, involving pathways such as biosynthesis of unsaturated fatty acids, the TCA cycle, and linoleic acid metabolism. Lipidomics results showed that 68 significantly different lipids were identified between the control and model groups, involving pathways such as omega-3/omega-6 fatty acid synthesis, T-cell receptor and costimulatory signaling, and G-protein-coupled receptor activation of PKC. After ACT treatment, significant changes were observed in 67 differential lipids, with notable reversal in the aforementioned pathways. It also regulated PPARα modulation of lipid metabolism and related pathways such as α-linolenic acid and linoleic acid metabolism. Correlation analysis of differential metabolites and lipids indicated that metabolites such as homovanillic acid, palmitic acid, indoxyl sulfate, as well as triglycerides and phosphatidylcholines were critical. The commonly regulated pathways by non-targeted metabolomics and lipidomics were biosynthesis of unsaturated fatty acids and linoleic acid metabolism. In conclusion, ACT primarily treats CGN in young rats by regulating the biosynthesis of unsaturated fatty acids and linoleic acid metabolism pathways through differential lipids such as triglycerides and some phosphatidylcholines, and differential metabolites such as homovanillic acid, palmitic acid, and indoxyl sulfate. This study initially elucidated the intervention mechanism of ACT in the treatment of pediatric chronic glomerulonephritis from the perspective of serum metabolism, laying a solid foundation for the rational clinical application of ACT in children with CGN.