Akebia Saponin D ameliorated kidney injury and exerted anti-inflammatory and anti-apoptotic effects in diabetic nephropathy by activation of NRF2/HO-1 and inhibition of NF-KB pathway

• Published in: International immunopharmacology Vol. 84; p. 106467
• Main Authors: Lu, Congcong, Fan, Guoxia, Wang, Dianyun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2020; Elsevier BV
• Subjects: Activation; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Akebia; Akebia Saponin D; Animals; Anti-apoptosis; Anti-inflammation; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Blood; Blood glucose; Cell Line; Clear cell-type renal cell carcinoma; Creatinine; Damage prevention; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetic Nephropathies - chemically induced; Diabetic Nephropathies - drug therapy; Diabetic nephropathy; Epithelial Cells - metabolism; Humans; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Insulin; Kidney - drug effects; Kidney injury; Kidneys; Male; Mice; Mice, Inbred C57BL; Microvasculature; Morbidity; Nephropathy; NF-E2-Related Factor 2 - metabolism; NF-kappa B - antagonists & inhibitors; NF-KB; NF-κB protein; NRF2/HO-1; Oxidative stress; Oxidative Stress - drug effects; Renal function; Saponins; Saponins - pharmacology; Saponins - therapeutic use; Signal Transduction - drug effects; Urea; NRF2/HO-1; Akebia Saponin D; NF-KB; Diabetic nephropathy; Anti-apoptosis; Kidney injury; Anti-inflammation
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2020.106467

•ASD suppress TNF-α, IL-1β and COX-2 in brain by activating NF-κB pathway.•Aqueous extract of Dipsaci Radix exerts anti-inflammatory, anti-oxidative effects.•NF-κB and NRF2/HO-1 pathways can adjust inflammation and oxidative stress. Diabetic nephropathy (DN), a common microvascular complication of type 2 diabetes mellitus (T2DM), causes increasing mortality and morbidity due to its high prevalence and severe consequences. Hence, it is urgent to search for effective agents that provide new insights into novel molecular therapeutic targets for DN. This study was designed to investigate the critical role of Akebia saponin D (ASD) in kidney damage, inflammation and apoptosis of renal tubular cells in DN. To probe the protective effects of ASD on DN in vivo, diabetes mellitus model was established by intraperitoneal (ip) injection of STZ (60 mg/kg) for 5 days consecutively. Besides, HG-induced human renal tubular cells (HK-2) were used to analyze the defined effects and underlying mechanism of ASD on DN in vitro. Blood glucose, insulin, serum creatinine (Scr), blood urea nitrogen (BUN), renal injury, inflammation, oxidative stress and apoptosis of renal tubular cells were respectively measured and evaluated. ASD prevented kidney damage, improved renal function and inflammatory reaction, ameliorated oxidative stress and inhibited apoptosis of renal tubular cells in DN mice via activation of NRF2/HO-1 pathway and inhibition of NF-KB pathway.