Oridonin Attenuates Lipopolysaccharide‐Induced ROS Accumulation and Inflammation in HK‐2 Cells
Jen-Hsuan Huang, Chou‐Chin Lan, Ya‐Ting Hsu, Cheng-Lin Tsai, I‐Shiang Tzeng, Po Wang, Chan‐Yen Kuo, Po‐Chun Hsieh
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‐ κ B 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.