Metabolomic Analysis of Stephania tetrandra-Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

被引:6
|
作者
Xu, Baiyang [1 ]
Yao, Mengxue [1 ]
Liu, Zilu [1 ]
Zhang, Shanshan [1 ]
Wang, Bin [1 ]
Han, Yanquan [2 ]
Gao, Jiarong [2 ]
Wu, Deling [1 ,3 ,4 ]
Wang, Xiaoli [1 ,3 ,4 ]
机构
[1] Anhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei 230031, Peoples R China
[2] Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230031, Peoples R China
[3] Anhui Prov Key Lab Tradit Chinese Med Decoct Piece, Bozhou 236800, Peoples R China
[4] Anhui Prov Key Lab Res & Dev Chinese Med, Hefei 230012, Peoples R China
关键词
Stephania tetrandra; Astragalus membranaceus; herbal pair; nephrotic syndrome; untargeted metabolomics; IL-13; STAT6 signal pathway; PERFORMANCE LIQUID-CHROMATOGRAPHY; FANGJI HUANGQI TANG; SYNDROME MECHANISMS; INJURY; HOMOCYSTEINE; INFLAMMATION; EXPRESSION; PLASMA;
D O I
10.3390/ph16010088
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The Stephania tetrandra-Astragalus membranaceus herbal pair (FH) is a classic herbal pair widely used in the treatment of nephrotic syndrome (NS). The effects of Stephania tetrandra (FJ) and Astragalus membranaceus (HQ) on NS have been reported, but the mechanism of their combination on the improvement of NS are still unclear. The NS model was established by injecting adriamycin into the tail vein. FH intervention reduced the levels of serum triglyceride, total cholesterol, interleukin-6 (IL-6), blood urea nitrogen (BUN), urinary protein, and the gene expression levels of aquaporin 2 (AQP2) and arginine vasopressin (AVP) in NS rats. In addition, FH improved kidney injury in NS rats by inhibiting the expression of interleukin 13 (IL-13), phospho-signal transducers, and activators of transcription 6 (p-STAT6), Bax, cleaved-caspase3, while promoting the expression of Bcl-2. By comprehensive comparison of multiple indexes, the effects of FH on lipid metabolism, glomerular filtration rate, and inflammation were superior to that of FJ and HQ. Metabonomic studies showed that, compared with FJ and HQ, FH intervention significantly regulated tricarboxylic acid (TCA) cycle, cysteine and methionine metabolism, and alanine, aspartic acid and glutamic acid metabolism. Pearson correlation analysis showed that succinic acid and L-aspartic acid were negatively correlated with urinary protein, cystatin C (Cys C) and BUN (p < 0.05). In summary, FH could reduce renal injury and improve NS through inhibiting the IL-13/STAT6 signal pathway, regulating endogenous metabolic pathways, such as TCA cycle, and inhibiting the expression of AQP2 and AVP genes. This study provides a comprehensive strategy to reveal the mechanism of FH on the treatment of NS, and also provides a reasonable way to clarify the compatibility of traditional Chinese medicine.
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页数:18
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