Abstract
Ischemia-reperfusion injury is one of the major causes of acute kidney injury (AKI), which is increasingly prevalent in clinical settings. Glaucocalxin A (GLA), a biologically ent-kauranoid diterpenoid, has various pharmacological effects like antioxidation, immune regulation, and antiatherosclerosis. In this study, the effect of GLA on AKI and its mechanism were studied in vitro. HK-2 human renal tubular epithelial cells were exposed to hypoxia/reoxygenation (H/R), which were established as an in vitro AKI model. Subsequently, the mRNA expressions of inflammatory and antioxidant factors were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production and cell death were detected by fluorescence-activated cell sorting. GLA pre-treatment improved the cell viability of HK-2 cells exposed to H/R. GLA suppressed the H/R-induced ROS production in HK-2 cells. GLA also elevated the activities of superoxide dismutase of HK-2 cells exposed to H/R. Moreover, GLA prevented H/R-induced cell death in HK-2 cells. Furthermore, GLA ameliorated the activation of the protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in HK-2 cells exposed to H/R. Our findings suggested that GLA protected HK-2 cells from H/R-induced oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. These results indicate that GLA may serve as a promising therapeutic drug for AKI.
Highlights
Published: 31 December 2021Glaucocalyxin A (GLA) is a natural diterpenoid compound isolated from Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, which is widely distributed in EastAsia
We assessed the cytotoxic effects of Glaucocalxin A (GLA) on HK-2 cells using an lactic dehydrogenase (LDH) leakage assay
Exposure significantly decreased viability of HK-2 cells compared with control, which ameliorated by pre-incubation with GLA 5 μM
Summary
Published: 31 December 2021Glaucocalyxin A (GLA) is a natural diterpenoid compound isolated from Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, which is widely distributed in EastAsia. GLA has been used from a long time ago as a traditional medicine for gastrointestinal disorders and inflammation [1]. It has been reported that GLA inhibits various pharmacological effects. GLA exhibits anti-cancer [2], antioxidative [3], anti-inflammatory [4], and anti-fibrotic [5] effects. GLA has been shown a possible potential therapeutic agent for microglia-mediated neuroinflammatory diseases via inhibition of the NF-κB and p38 signaling pathways [4]. GLA has been shown to reduce lipopolysaccharide-induced septic shock and inflammation via suppressing the activation of NLRP3 and NLRC4 inflammasomes. There are a few reports about the ameliorating effects of GLA on kidney injuries
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