Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Abstract

Background. Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats. Methods. Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n=8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot. Results. In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats. Conclusion. AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy

“…Nevertheless, effective treatments remain scarce. Previous studies have been demonstrated that AR and PN play a critical role in treating DN [ 12 – 14 , 50 ], suggesting AR-PN may be a potential herb pair for the treatment of DN. For all we know, this is the first study to perform a comprehensive analysis of network pharmacology combined with gene expression profiling to further explore the underlying pharmacological mechanisms and therapeutic targets of the AR-PN herb pair on DN.…”

“…AR - PN , a classic highly valued and widely used herb pair, is well known to possess functions with tonifying qi and activating blood circulation. Modern pharmacological research shows that AR treatment ameliorated the severity of DN by inhibiting inflammation-related gene IL-1 β and IL-18 expression and fibrosis indexes in DN rats [ 12 ]. Likewise, it has been confirmed that AR possesses antioxidative stress effects [ 13 ].…”

Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy

“…Fresh kidney tissue was homogenized in phosphate-buffered saline (PBS) and centrifuged. After total protein quantification, renal tissue samples were used for enzyme-linked immunosorbent assay (ELISA) measurement[ 27 ]. At the same time, cell culture supernatant was collected.…”

Network Pharmacology-Based Investigation into the Mechanisms of Qibangyishen Formula for the Treatment of Diabetic Kidney Disease

“…Speci cally, DI HUANG reduces blood sugar, serum triglycerides, uric acid, and the 24-hour urine albumin excretion rate, increases high density lipoprotein, interferes with in ammation, signi cantly 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][29][30]. SAN QI regulates sugar metabolism, has anti-brosis, antioxidation and anti-in ammatory effects, improves kidney function, and delays kidney damage [31,32].…”