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Abstract
As for traditional Chinese medicine (TCM) prescription, what puzzled researchers most was how to select proper chemical markers to represent the whole pharmacological action system. In this paper, an integrated metabolomic method was presented for a systematic discovery of potential active components in Fangji Huangqi Tang (FHT), a well-known TCM prescription for nephrotic syndrome treatment, based on “correlations between chemical and metabolic profiles.” Firstly, a metabolomics study was carried out to select representative biomarkers of nephrotic syndrome. Then, after drug administration, the dynamic process of serum composition was investigated by the ultra-high performance liquid chromatography coupled with electrospray ionization–quadrupole–time of flight–mass spectrometry (UHPLC-ESI-Q-TOF-MS) technique to detect the prototypes and related metabolites of relative components from FHT. Pearson correlation analysis was finally used to find out the correlations between the endogenous metabolic spectrums and the chemical serum spectrums. As a result, 17 biomarkers for nephrotic syndrome indication were identified, and the main metabolic pathways of their concern included linoleic acid metabolism; cyanoamino acid metabolism; alpha-linolenic acid metabolism; glycine, serine, and threonine metabolism; arachidonic acid metabolism; and glycerophospholipid metabolism. Meanwhile, active components in FHT for nephrotic syndrome treatment were screened out, including (+)-tetrandrine demethylation, fenfangjine G hydrogenation, tetrandrine, N-methylfangchinoline, tetrandrine demethylation, fangchinoline, glycyrrhetic acid, astragaloside II alcohol dehydration, atractylenolide III demethylation + hydrogenation, atractylenolide III demethylation + hydrogenation, and licoricone-N-acetylcysteine conjugation. This study demonstrated a promising way to elucidate the active chemical material basis of TCM prescription.
Highlights
Nephrotic syndrome is a common disease of the urinary system, which could be divided into primary and secondary types, with clinical manifestations such as proteinuria, hypoalbuminemia, edema, and hyperlipidemia
Nephrotic Syndrome Modeling The biomedical indexes of rats for nephrotic syndrome indication in the normal and model groups, such as urinary protein, Total cholesterol (TC), TG, blood urea nitrogen (BUN), and cystatin C (Cys C), were investigated firstly to determine whether the nephrotic syndrome model was constructed successfully
The results are shown in Supplementary Table 1. Compared with those in the normal group, 24 h urine protein, TC, TG, BUN, and Cys C levels in the model group were obviously elevated, which indicated that the nephrotic syndrome model was successfully induced
Summary
Nephrotic syndrome is a common disease of the urinary system, which could be divided into primary and secondary types, with clinical manifestations such as proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Traditional Chinese medicine (TCM) had some special advantages in treating nephrotic syndrome, especially in the aspects of reducing proteinuria and side effects of immunosuppressive drugs, as well as alleviating the complications of hypercoagulability or gastrointestinal mucosa edema (Wang and Wang, 2004; Nie, 2008; Wu et al, 2014). Compared with hormone, TCM application to treatment of nephrotic syndrome is a good way to avoid side effects and to reduce high recurrence rate of disease. Underlying active components and modern therapeutic mechanisms of FHT for nephrotic syndrome are still unclear
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