Diabetic kidney disease (DKD) is a chronic disease caused by diabetes and has a complicated pathogenesis [1–3]. The clinical features include continuously increasing excretion of albuminuria and/or glomerular filtration rate (GFR) less than 60 ml/(min·1.73m2) for more than 3 months, which can eventually develop into end-stage renal disease (ESRD). Diabetic kidney disease leads to about 30–50% ESRD cases worldwide [4, 5] and is the leading cause of ESRD in middle-aged and elderly people in China [6, 7].
There are many clinical treatments for diabetic kidney disease [2, 8, 9], including life management [10, 11], blood sugar control [12, 13], blood pressure control [14, 15], blood lipid regulation [16, 17], uric acid control [18, 19], and proteinuria regulation [20]. These treatments have various degrees of efficacy, but many patients with DKD continue to progress to dialysis. Traditional Chinese medicine has also been widely used to treat diabetic kidney disease. Chinese medicine may improve kidney and immune function and elicit therapeutic effects [21–23]. Diabetic kidney disease has no precise definition in ancient Chinese medical literature, but according to etiology and pathogenesis, diabetic kidney disease can be attributed to "edema" and "guange" secondary to Xiaoke. Huang et al. [24] found that QufengTongluo Formula and YiqiHuayu Formula delay renal fibrosis and reduce urine protein in DKD rats, which may be related to enhanced PTEN expression, inhibition of PI3K/Akt signaling, and reduced transforming growth factor-β (TGF-β) expression. Hong et al. [25] showed that Jiangtang Formula reduces the level of advanced glycosylation products in KK-Ay mice and increases the phosphorylation of PI3K and Akt, which reduces inflammatory responses in DKD rats.
Qibangyishen Formula (QBYSF) is composed of DI HUANG (Rehmannia glutinosa Libosch.), HUANG QI (Astragalus membranaceus(Fisch.)Bge.), SAN QI (Panax notoginseng(Burk.)F. H. Chen), NIU BANG ZI (Arctium lappa L.), BAI SHAO (Paeonia lactiflora Pall.) and HEI DOU (Glycine max(L.)Merr.). QBYSF has been clinically used to treat diabetic kidney disease, and ingredients within QBYSF have been shown to have beneficial effects. Specifically, DI HUANG reduces blood sugar, serum triglycerides, uric acid, and the 24-hour urine albumin excretion rate, increases high density lipoprotein, interferes with inflammation, significantly improves serum creatinine and urea nitrogen, and protects patients' renal function [26, 27]. HUANG QI reduces blood sugar, uric acid, urea nitrogen, and blood creatinine, improves proteinuria, and has a protective effect on the kidneys [28–30]. SAN QI regulates sugar metabolism, has anti-fibrosis, anti-oxidation and anti-inflammatory effects, improves kidney function, and delays kidney damage [31, 32]. Previously, we found that HUANG QI combined with SAN QI reduces urinary protein excretion, decreases renal pathological changes, and improves apoptosis and shedding of kidney podocytes in DKD rats [33]. NIU BANG ZI extract reduces podocyte damage and proteinuria symptoms of DKD mice by enhancing PP2A activity in podocytes and protects kidney function [34].NIU BANG ZI extract also significantly reduces blood sugar in DKD mice and reduces the damage to the kidney [35]. Total glycosides is the main component of the BAI SHAO and reduces serum hs-CRP, TNF-α, and MCP-1 levels in patients with DKD, thereby protecting the kidneys [36]. Peony total glucosides prevent renal tubular interstitial damage in rats with diabetic nephropathy and delay the development of diabetic nephropathy [37]. HEI DOU reduces blood sugar, blood lipids, serum creatinine, and blood urea nitrogen in streptozotocin (STZ)-induced diabetic rats [38], and long-term low-dose HEI DOU protects diabetic renal insufficiency [39]. Although, the effects of individual components of QBYSF have been examined in diabetic murine models and in patients, the mechanism of QBYSF on diabetic kidney disease is not clear yet.
This study uses network pharmacology to screen the main active ingredients, targets, and pathways of QBYSF to analyze its mechanism on the treatment of diabetic kidney disease.