Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO‐1 signalling pathway

Abstract

Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK‐2. HK‐2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R‐stimulated HK‐2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R‐stimulated HK‐2 cells. In addition, AR also presented an anti‐inflammatory activity, as evidenced by decreased secretion of pro‐inflammatory cytokines including IL‐6, IL‐1β, and TNF‐α. Moreover, apoptotic rate was markedly decreased in HK‐2 cells pretreated with AR. The bax expression was decreased, while bcl‐2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R‐stimulated activation of the Nrf2/HO‐1 signalling pathway in HK‐2 cells. In conclusion, these findings indicated that AR protected HK‐2 cells from H/R‐induced cell injury via regulating the Nrf2/HO‐1 signalling pathway.

miR‑30a‑5p inhibits hypoxia/reoxygenation‑induced oxidative stress and apoptosis in HK‑2 renal tubular epithelial cells by targeting glutamate dehydrogenase 1 (GLUD1)

“…Acute kidney injury (AKI) is currently the main cause of high mortality in patients with acute disease ( 1 ). In recent years, the molecular and pathological mechanisms of AKI has been elucidated; however, most studies were focused on signaling pathways such as the PI3K/Akt ( 2 ), Nrf2/HO-1 ( 3 ), and TLR4/NF-κB ( 4 ) pathways. MicroRNAs (miRNAs) have been reported to play a vital regulatory role in many physiological pathways, including multiple acute tissue injury, for example the miR-30b-3p pathway, which is involved in acute lung injury ( 5 ) and the miR-30a-5p pathway, which can alleviate inflammatory responses and oxidative stress stimulated by spinal cord injury by targeting the Neurod 1/MAPK/ERK axis ( 6 ).…”

Effect of Circhipk3 on Polarization of Microglial Cells in Nerve Injury Caused by Heat Radiation

“…[14]. Previous studies have focused on inhibiting myocardial fibrosis and delaying myocardial remodeling [15], and high glycemic podocyte damage has confirmed that HO-1 is involved in upregulation of autophagy [16] and induction of renal tubular epithelial cells during renal injury [17]. We found that HO-1 in the HS 0.8 and HS 8 groups was significantly higher than that in the normal group, and HO-1 in the HS 24 group was significantly lower than that in the normal group.…”

Wan-Nian-Qing, a Herbal Composite Prescription, Suppresses the Progression of Liver Cancer in Mice by Regulating Immune Response

“…Activated Nrf2 can modulate cellular antioxidant regulators; it can upregulate the expression of HO-1, SOD-1, and other downstream genes in normal cells to maintain the intracellular redox balance and reduce tumorigenesis ( 39 ). Activated Nrf2 is involved in the regulation of immune factors ( 40 , 41 ), which it achieves by inducing T lymphocytes to produce ILs, interferons, and TNF ( 42 ). In our previous experiments, we showed that Antrodia cinnamomea polysaccharides (APCS) enhance immune functions in mice by upregulating the expression of Nrf2 ( 43 ).…”