Abstract
BackgroundBupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD). However, the mechanism of action of BYF has not been fully elucidated.MethodTo investigate the variation in the metabolic profile in response to BYF treatment in a rat model of 5/6 nephrectomy (Nx), rats in the treatment groups received low- or high-dose BYF. At the end of the study, serum and kidney samples were collected for biochemical, pathological, and western blotting analysis. Metabolic changes in serum were analyzed by liquid chromatography-tandem mass spectrometry.ResultsThe results showed that BYF treatment could reduce kidney injury, inhibit inflammation and improve renal function in a dose-dependent manner. In total, 405 and 195 metabolites were identified in negative and positive ion modes, respectively. Metabolic pathway enrichment analysis of differential metabolites based on the Kyoto Encyclopedia of Genes and Genomes database identified 35 metabolic pathways, 3 of which were related to tryptophan metabolism. High-dose BYF reduced the level of kynurenic acid (KA) by more than 50%, while increasing melatonin 25-fold and indole-3-acetic acid twofold. Expression levels of aryl hydrocarbon receptor (AhR), Cyp1A1, and CyP1B1 were significantly reduced in the kidney tissue of rats with high-dose BYF, compared to 5/6 Nx rats.ConclusionBYF has a reno-protective effect against 5/6 Nx-induced CKD, which may be mediated via inhibition of the tryptophan-KA-AhR pathway.
Highlights
Bupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD)
BYF has a reno-protective effect against 5/6 Nx-induced CKD, which may be mediated via inhibition of the tryptophan-kynurenic acid (KA)-aryl hydrocarbon receptor (AhR) pathway
quality control (QC) of BYF High-performance liquid chromatography (HPLC) indicated that the major components in BYF were similar between this study and the previous study, as shown in Suppl
Summary
Bupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD). Bupi Yishen Formula (BYF) is a patent TCM formulation modified from the historical TCM prescription, Si-jun-zi Decoction It was developed based on the results of text mining of medical records from Guangdong Provincial Hospital of Chinese Medicine, a tertiary hospital in southern China. BYF contains nine herbal medicines, including Astragalus mongholicus (Huangqi), Codonopsis pilosula (Dangshen), Atractylodes macrocephala (Baizhu), Poria cocos (Fuling), Dioscorea opposita (Shanyao), Coici semen (Yiyiren), Polygonum multiflorum (Heshouwu), Cuscuta Chinensis (Tusizi), and Salvia miltiorrhiza (Danshen). Astragalus mongholicus (Huangqi) and Salvia miltiorrhiza (Danshen), a commonly used drug pair for clinical treatment of CKD in traditional Chinese medicine with good efficacy, markedly reduced serum creatinine and urea nitrogen, and ameliorated tubular atrophy and interstitial fibrosis in CKD rats [7]. The underlying mechanism of the effect of BYF on CKD is unclear
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