A Novel Approach Based on Metabolomics Coupled With Intestinal Flora Analysis and Network Pharmacology to Explain the Mechanisms of Action of Bekhogainsam Decoction in the Improvement of Symptoms of Streptozotocin-Induced Diabetic Nephropathy in Mice

Abstract

Bekhogainsam decoction (BHID), a representative prescription for the treatment of diabetes mellitus (DM) and diabetic complications in both traditional Korean and Chinese medicine, was examined for its ability to ameliorate diabetic nephropathy (DN), and its mechanism of action was evaluated by metabolomics, gut microbiota, and network pharmacology. In this study, male specific pathogen-free C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ, 100 mg/kg) once per day for 3 days consecutively, and were then orally administered BHID at 100 and 500 mg/kg, and metformin at 250 mg/kg once per day for 4 weeks. Our results showed that the administration of BHID to mice with STZ-induced DN prevented physiological and serological changes, structural damage, and kidney dysfunction. Based on a metabolomics test with serum, the profoundly altered metabolites in the BHID treatment group were identified. Thirty-six BHID-related proteins and four signaling pathways, including valine, leucine, and isoleucine biosynthesis, nicotinate and nicotinamide metabolism, tryptophan metabolism, and alanine, aspartate, and glutamate metabolism pathways, were explored. Principal coordinates analysis (PCoA) of the gut microbiota revealed that BHID treatment significantly affected the flora composition. In addition, the network pharmacology analysis revealed that BHID acted through phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and MAPK-related protein targets. Our findings on the anti-DN effects of BHID and its mechanism of

Phillyrin ameliorates diabetic nephropathy through the PI3K/Akt/GSK-3β signalling pathway in streptozotocin-induced diabetic mice

“…After 1 week of acclimation, followed by fasting for 12 h, DN mouse models were induced by single intraperitoneal injection of 100 mg/kg STZ, [29][30][31][32] while the normal control mice were injected with the same amount of citrate buffer. Blood samples were obtained from the tails of the mice, and fasting blood glucose (FBG) levels were measured with a glucometer (Sinocare Inc., Hunan, China).…”

Recent advances of gut microbiota in chronic kidney disease patients

“…Therefore, the dysbiosis of gut microbiota has a critical effect on DKD. Increased evidence has demonstrated that a number of natural products could improve the dysbiosis of gut microbiota in DKD [68][69][70][71][72].…”

Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM)

“…In a recent study, Meng and colleagues proved that Bekhogainsam decoction (BHID) affected the intestinal flora of DN mice, acting through phosphatidylinositol-3-kinase/protein kinase B and other protein targets related to MAPK. It also prevented kidney dysfunction, making it a great support in the clinical treatment of diabetic patients [162]. Jowiseungki decoction (JSD) is another possible option for ameliorating DN symptoms.…”