Oridonin Attenuates Lipopolysaccharide‐Induced ROS Accumulation and Inflammation in HK‐2 Cells

Abstract

Renal tubulointerstitial inflammation plays an important role in chronic kidney disease (CKD). Inflammation reduction is a good strategy to combat CKD. Oridonin, an ent-kaurane diterpenoid isolated from Rabdosia rubescens (Donglingcao), is considered as an effective natural candidate for the treatment of anti-inflammatory, antiviral, and antibacterial activities, including liver fibrosis and many tumors; however, no study has demonstrated its effect on lipopolysaccharide- (LPS-) induced renal inflammation. To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells (HK-2 cells), the expression levels of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) were evaluated by Western blot analysis and 2′,7′-dichlorofluorescein diacetate (DCF-DA) staining, respectively. The level of intracellular ROS increased in a dose-dependent manner following LPS treatment, whereas oridonin inhibited this effect, suggestive of its ability to prevent ROS accumulation. As the mitogen-activated protein kinase (MAPK) family of enzymes plays an important role in physiological responses, we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation. Oridonin also attenuated RAW 264.7 cell chemotaxis towards LPS-treated HK-2 cells. Taken together, oridonin protected against LPS-induced inflammation including ROS accumulation, JNK activation, NF-κB nuclear translocation in HK-2 cells, and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells. Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells.

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

“…Therefore, further study on the mechanism of renal immunity and in ammation and search for drugs to inhibit immune in ammatory response may nd new targets for DN anti-in ammatory therapy. Natural antiin ammatory products are a safe alternative to traditional methods for regulating in ammatory diseases [25][26][27][28] .…”

Loss of Function of von Hippel‐Lindau Trigger Lipocalin 2‐Dependent Inflammatory Responses in Cultured and Primary Renal Tubular Cells

“…The analysis of the measurement of intracellular ROS generation was according to our previous studies with some modifications [ 23 ]. The cells were washed with phosphate-buffered saline (PBS) and incubated with 10 μ M dihydroethidium (DHE; Santa Cruz, Dallas, TX, USA) in Hank's balanced salt solution at 37°C for 30 minutes in the dark.…”

“…The chemotaxis analysis was according to our previous studies with some modifications [ 23 ]. Nuclear fractions were extracted from the HK-2 or mRTC cells.…”

“…Chemotaxis Assay. The chemotaxis analysis was according to our previous studies with some modifications [23]. A 24-well Transwell plate (8 μm pore size, Corning, NY, USA) was used to measure the chemotactic ability of the RAW274.7 cells.…”

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity

“…These specific manifestations includes reducing lung injury scores, releasing of cytokines, neutrophil infiltration, exudating volume and the exudate protein concentration, decreasing the levels of oxidative stress markers ( Yang et al, 2020 ). Recently, researcher relies on the fact that oridonin itself can act as a protective agent against LPS-induced inflammatory response, which the specific mechanisms involve in ROS accumulation, JNK activation, nuclear translocation of NF- κ B ( Huang et al, 2020 ). Oridonin also inhibits autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes ( He et al, 2020 ).…”