RESUMO
The cellular defense pathway plays a key role in maintaining the homeostasis, tissues and organisms. Nuclear factor E2-related factor 2 (Nrf2), as a key cell signaling pathway, plays an important role in encoding detoxification enzymes and other stress response mediators. Recent studies have shown that it is closely related to the prevention and treatment of acute kidney injury (AKI). Therefore, this article reviews the protective effects of Nrf2-related signaling pathways on acute kidney injury, and summarizes the strategies of natural pharmaceutical ingredients such as flavonoids, alkaloids, terpenes, phenylpropionic acid, polyphenols, and polysaccharides to prevent and treat acute kidney injury. It is of great significance to further study the relationship between Nrf2 regulated signal pathway and kidney disease and the development of new medicines for acute kidney injury treatment. It can also provide new ideas and treatment strategies for clinical treatment of acute kidney injury. PRACTICAL APPLICATIONS: This article reviewed the mechanisms by which the active ingredients of natural medicines slow down acute kidney injury through the Nrf2 pathway. It will help us to understand the regulatory role of the Nrf2 pathway in AKI more comprehensively, and provide a theoretical basis for further exploring the mechanism of more natural drugs to reduce acute kidney injury.
Assuntos
Injúria Renal Aguda , Alcaloides , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Flavonoides , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de SinaisRESUMO
Acetaminophen (APAP)-induced acute kidney injury (AKI) has turned into a typical reason for clinic obtained renal disappointment. In any case, the advancement of prophylaxis procedures and endorsed treatments for APAP-AKI is restricted. Sika deer antler protein (SDAPR) has a protective effect on drug-induced AKI. The reason for this investigation was to clarify the material premise and atomic instrument of the defensive impact of SDAPR on APAP-induced AKI. We conducted column chromatography on SDAPR extracted with Sephadex G-100 and obtained proteins of 2 different components named sika deer antler protein 1 (SDAP1) and sika deer antler protein 2 (SDAP2), respectively. MTT assay and xCELLigence Real-Time Cell Analysis showed that SDAPR, SDAP1 and SDAP2 had protective effects on APAP-induced cytotoxicity in Human kidney tubular epithelial (HK-2) cells. Therefore, we conducted proteomic analysis on SDAPR, SDAP1 and SDAP2. What's more, we inspected them viability of avoiding renal damage in APAP mice and HK-2 cells model. Contrasted and saline, SDAPR, SDAP1 and SDAP2 pretreatment portion conditionally fundamentally constricted heights in kidney damage Markers and the histological changes of renal cylindrical wounds, diminished the quantity of apoptosis-positive rounded cells, initiated NF-E2 p45-related factor 2 (Nrf2), inhibition Forkhead box O 1 transcription factors (FoxO1) and brought down the degrees of renal oxidative stress and apoptosis prompted by APAP. The above security of SDAPR, SDAP1 and SDAP2 was nullified by the Phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) in HK-2 cells. In this manner, our outcomes exhibit that, SDAPR, SDAP1 and SDAP2 against APAP-induced oxidative stress and apoptosis by initiating Nrf2 and restraint FoxO1 through PI3K/Akt signaling.