Notoginsenoside Fc ameliorates renal tubular injury and mitochondrial damage in acetaminophen-induced acute kidney injury partly by regulating SIRT3/SOD2 pathway

Abstract

IntroductionMitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied.MethodsIn this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI.ResultsOur results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP.ConclusionIn summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.

Mitigating Acetaminophen-Induced Kidney Injury: The Protective Role of Grape Seed and Peanut Skin Extracts through the iNOS/CYP2E1 Pathway

“…This dramatic rise in creatinine and urea levels demonstrated, in this investigation, that APAP overdose-induced renal dysfunction and nephrotoxicity as nitrogen wastes in serum were in harmony with many studies that suggested increased oxidative stress and inflammation outputs as main and intermediate promoters. 2,55 In renal diseases, urea, and creatinine accumulate in serum not because of intensified production but because of a decreased clearance rate, indicating a defect in renal function. 56 Kidney damage from acetaminophen (APAP) toxicity involves multiple pathways.…”

Untargeted Metabolomics Approach for the Differentiation between Panax vietnamensis var. vietnamensis and Panax vietnamensis var. fuscidiscus

“…Nonetheless, the distinct ginsenoside levels suggested that using ginsenosides alone could still be sufficient to classify PVV and PVF (Figure 6). Among the markers, OT-type saponins such as M-R2 and V-R2 have been known mainly for their anti-inflammatory effects [25], while other PPD-type saponins such as G-Rd, G-Rb1, G-Rb2, N-Fa, N-Fc and PPT-type saponins such as N-R1 have been reported with various pharmacological activities, including anti-amnestic and anti-aging [26], neuroprotective [27], reduction of renal tubular injury and mitochondrial dysfunction [28], anti-hyperlipidemic activities [29], anti-coagulation [30], etc. Usually, the differences in the metabolite composition of the herbal medicine are directly related to the differences in their clinical efficacy.…”

Optimization of Extraction and Separation Process of Notoginsenoside Fc from Panax notoginseng Leaves

“…It was reported that it could attenuate HG-induced vascular endothelial cell injury, partly through the upregulation of PPARγ [5]. Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of the SIRT3/SOD2 pathway [6]. Fc can accelerate reendothelialization and alleviate excessive neointimal formation following carotid artery injury in diabetic Sprague-Dawley rats in vivo [7].…”