Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model

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.

Ethanolic Leaf Extract of Centella asiatica L. Possesses Nephroprotection in an Animal Model of Nephrotoxicity

“…CA reduced vascular remodelling, glomeruli injury by increasing antifibrotic factor activity, and inflammatory biomarkers restored renal injury in nephrectomy animals. [21][22][23] Different protective mechanisms could be responsible for Centella asiatica's nephroprotective effects. Previous research suggested that triterpenoid present in CA increased the activity of antioxidant enzymes and nuclear factor erythroid-2-related factor 2.…”

Research progress of natural active compounds on improving podocyte function to reduce proteinuria in diabetic kidney disease

“…Proteinuria is often accompanied by the shedding of podocytes from the basement membrane. Studies have shown that podocyteuria often precedes proteinuria in several renal diseases including DKD [ 19 ]. Therefore, detection of urine containing exfoliated podocytes plays a role in the early diagnosis of DKD [ 20 ].…”

Hubungan Status Demografi, Komorbid Dengan KIPI Post Vaksin COVID-19 Pada Tenaga Kesehatan

“…Salah satunya responden yang memiliki penyakit penyerta. Mereka yang memiliki penyakit komorbid harus dalam kondisi terkontrol, Hal ini disebabkan orang-orang yang memiliki penyakit tertentu tidak memiliki daya tahan yang baik untuk membuat antibodi (Setyaningsih et al, 2021). Setiap vaksin COVID-19 mempunyai keunggulan dan kelemahan, baik dalam efektifitas, keamanan dan penyimpanan (Pawankar et al, 2021).…”