Abstract
San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic nephropathy (DN) in clinic. However, the mechanisms of SHYS on DN remain unknown. In this study, we used a high-fat diet (HFD) combined with streptozotocin (STZ) injection to establish a DN rat model. Next, we used 16S rRNA sequencing and untargeted metabolomics to study the potential mechanisms of SHYS on DN. Our results showed that SHYS treatment alleviated the body weight loss, hyperglycemia, proteinuria, pathological changes in kidney in DN rats. SHYS could also inhibite the oxidative stress and inflammatory response in kidney. 16S rRNA sequencing analysis showed that SHYS affected the beta diversity of gut microbiota community in DN model rats. SHYX could also decrease the Firmicutes to Bacteroidetes (F to B) ratio in phylum level. In genus level, SHYX treatment affected the relative abundances of Lactobacillus, Ruminococcaceae UCG-005, Allobaculum, Anaerovibrio, Bacteroides and Candidatus_Saccharimonas. Untargeted metabolomics analysis showed that SHYX treatment altered the serum metabolic profile in DN model rats through affecting the levels of guanidineacetic acid, L-kynurenine, prostaglandin F1α, threonine, creatine, acetylcholine and other 21 kind of metabolites. These metabolites are mainly involved in glycerophospholipid metabolism, tryptophan metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, tricarboxylic acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and D-glutamine and D-glutamate metabolism pathways. Spearman correlation analysis showed that Lactobacillus, Candidatus_Saccharimonas, Ruminococcaceae UCG-005, Anaerovibrio, Bacteroides, and Christensenellaceae_R-7_group were closely correlated with most of physiological data and the differential metabolites following SHYS treatment. In conclusion, our study revealed multiple ameliorative effects of SHYS on DN including the alleviation of hyperglycemia and the improvement of renal function, pathological changes in kidney, oxidative stress, and the inflammatory response. The mechanism of SHYS on DN may be related to the improvement of gut microbiota which regulates arginine biosynthesis, TCA cycle, tyrosine metabolism, and arginine and proline metabolism.
Highlights
Diabetic nephropathy (DN), major complications of diabetes, is a contributing factor in late-stage renal failure (Wang et al, 2016)
We used a high-fat diet (HFD) combined with STZ injection to establish a rat model of diabetic nephropathy (DN)
Compared with the Control group, the rats in the Model group exhibited a significant increase in FBG levels and there were abnormal biochemical indicators related to renal function, as manifested in increased serum Cr and blood urea nitrogen (BUN) as well as a significant increase in 24-h urine protein levels
Summary
Diabetic nephropathy (DN), major complications of diabetes, is a contributing factor in late-stage renal failure (Wang et al, 2016). The current treatment for DN includes blood glucose control and regulation of lipid metabolism using anti-hypertension medicines (Mann et al, 2010; Pazdro and Burgess, 2010; Tone et al, 2005; Jin et al, 2014). These conventional treatments do not completely prevent the progression of DN (Tuttle et al, 2018). Numerous studies have shown that TCM has significant advantages for improving renal function, controlling blood glucose levels, and inhibiting the inflammatory response on DN (Zhong et al, 2015). Xian-Zhen decoction decreases the accumulation of glycosylated products in renal tissues of rats with DN (Tang et al, 2005)
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