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Malaysian Journal of Medical Sciences 2019-Sep

Ethanol Extract of Centella asiatica (Gotu Kola) Attenuates Tubular Injury Through Inhibition of Inflammatory Cytokines and Enhancement of Anti-Fibrotic Factor in Mice with 5/6 Subtotal Nephrectomy.

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Nur Arfian
Wiwit Setyaningsih
Nungki Anggorowati
Muhammad Romi
Dwi Sari

Keywords

Abstract

Background
Chronic kidney disease (CKD) leads to inflammation, fibrosis and destruction of the renal architecture. Centella asiatica (CeA) is an herbaceous plant with anti-inflammatory effects. We aimed to elucidate the effect of CeA on inflammation, fibrosis, vascular remodelling and antifibrotic substances in a 5/6 subtotal nephrectomy (SN) model in mice.

Methods
Mice were divided into three groups: sham operation (SO, n = 6), 5/6 SN for seven days (SN7, n = 7) and SN7 with oral CeA treatment (SN7-CeA, n = 7). At day 7, mice were euthanised, kidneys were harvested and stained with periodic-acid Schiff (for tubular injury and glomerulosclerosis) and sirius red (for fibrosis and vascular remodeling) staining. mRNA expression of prepro-endothelin-1, nephrin, E-cadherin, bone morphogenic protein-7 (BMP-7), toll-like receptor 4 (TLR4), tumour necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) were quantified using reverse transcriptase-PCR.

Results
SN group demonstrated significant higher interstitial fibrosis, vascular remodeling, tubular injury and glomerulosclerosis (P < 0.01) compared to SO group. Meanwhile, in SN7-CeA demonstrated attenuation of vascular remodeling as shown by significant higher lumen area with lower Wall/Lumen area ratio compared to SN7. RT-PCR analysis showed up-regulation of nephrin, BMP-7 and E-cadherin mRNA expression (P < 0.05) and down-regulation of ppET-1 in SN7-CeA group compared to SN7 group (P < 0.05).

Conclusion
CeA may ameliorate renal injury in the SN model in mice.

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