Abstract

Background Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. Methods The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. Results The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. Conclusions Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.

Highlights

  • Diabetic nephropathy (DN) is one of the late complications of the diabetes mellitus (DM) and results in end-stage renal disease (ESRD) [1, 2]

  • We demonstrated that streptozotocin injection consistently elevated glucose level compared to the control group (p ≤ 0.001), and it lowered when the Centella asiatica (CeA) was administered. e CeA treatment at the early stage of DM (DMC2) significantly reduced glucose level compared to the DM2 (p 0.009)

  • The DM1C1 did not show any significant reduction of glucose level compared to DM groups. e proteinuria was obviously seen in the DM2 group compared to the control group (p ≤ 0.001) and DM1 group (p ≤ 0.001). e CeA treatment groups, either DMC2 or DM1C1, demonstrated a significant reduction of the proteinuria compared to the DM2 (p ≤ 0.001)

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Summary

Introduction

Diabetic nephropathy (DN) is one of the late complications of the diabetes mellitus (DM) and results in end-stage renal disease (ESRD) [1, 2]. Podocyte injury occurs since the early stage of DM and it dramatically worsens with the progressivity of diabetes. At the early stage of glomerular injury, the urinary expression of nephrin can be detected before the proteinuria [13, 14]. Several studies suggested that the treatment of high glucose increases TRPC6 in both the glomerulus and the heart which associated with ROS production and the renin-angiotensin system (RAS) activation [14, 19]. Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD).

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