Abstract
BackgroundAstragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS).MethodsDN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro.ResultsTreatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment.ConclusionsThese novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.
Highlights
Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), the underlying mechanisms still remain unclear
Two weeks after STZ injection, diabetic rats showed a significant increase in fasting blood glucose levels when compared with the control rats
Compared to AS-IV-L rats, AS-IV-H rats showed a better beneficial effect on reduction of blood glucose, suggesting that the 10 mg kg− 1 d− 1 dose of AS-IV might be the better choice for DN treatment
Summary
Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), the underlying mechanisms still remain unclear. A variety of animal models have been established and utilized to investigate DN [2]. It was shown that NO produced by endothelial cells plays a vital role in DN, which led to endothelial dysfunction in diabetes mellitus by inhibiting eNOS and reducing the production and bioavailability of NO [4,5,6]. A clinical study has reported that low eNOS expression is closely related to the occurrence of DN [7] .insufficient eNOS was found to accelerate the occurrence of nephropathy in both type 1 and type 2 diabetic mouse models [8,9,10]. Fan et al BMC Complementary and Alternative Medicine (2019) 19:355
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