Renoprotective Effect of Oridonin in a Mouse Model of Acute Kidney Injury <i>via</i> Suppression of Macrophage Involved Inflammation

Abstract

Ischemia-reperfusion injury (IRI) is the major cause of acute kidney injury (AKI). The previous studies demonstrated thatOridonin can protect kidney against IRI-induced AKI, but the underlying molecular mechanism is unclear. In this study, it showed that Oridonin significantly improved kidney damage, and inhibited the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and MCP-1, as well as macrophage marker F4/80 in kidney and the secretion of inflammatory cytokins in serum of AKI mice in vivo. In addition, Oridonin also effectively reduced the expression and secretion of lipopolysaccharide (LPS)-induced inflammatory factors in macrophage cell line RAW264.7 in vitro. Notably, Oridonin strongly downregulated Mincle and AKT/nuclear factor-kappaB (NF-κB) signaling both in vivo and in vitro, and the results of cellular recovery experiments of overexpression of Mincle in macrophage suggested that Oridonin suppressed inflammatory response of macrophage through inhibiting Mincle, which may be the underlying mechanism of Oridonin improving injury in kidney of AKI mice. In summary, the above results indicated that Oridonin can protect kidney from IRI-induced inflammation and injury by inhibiting the expression of Mincle in macrophage.

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

“…Increased infiltration of macrophages and CD4 + T cells was also alleviated by oridonin. Consistently, emerging evidence suggest that the beneficial action of oridonin on renal ischemia-reperfusion injury is associated with suppression of macrophage-mediated inflammation [ 10 , 11 ]. It has been also reported that oridonin can modulate the activation and proliferation of T cells to alleviate inflammatory diseases such as inflammatory bowel disease [ 46 , 47 ] and asthma [ 48 ].…”

“…Besides nephrotoxic medications, ischemia-reperfusion injury is also a major cause of AKI [ 24 ]. Recent studies have demonstrated the protective effect of oridonin on renal ischemia-reperfusion injury [ 10 , 11 ]. These findings suggest that the beneficial action of oridonin is not limited to cisplatin-induced AKI but may also be applied to other types of AKI.…”

“…All mice were sacrificed 72 hours after a single dose of cisplatin. The doses of oridonin and cisplatin were selected based on the results of previous studies [ 10 , 13 ]. All animal procedures were approved by the Institutional Animal Care and Use Committee of the Daegu Catholic University Medical Center (DCIAFCR-200626-12-Y).…”

“…Accumulating evidence suggest that oridonin has potent anticancer, antioxidative, and anti-inflammatory activities [ 7 – 9 ]. Although many studies have focused on elucidating the antitumor effect of oridonin [ 7 ], emerging evidence suggest that the compound inhibits renal ischemia-reperfusion injury in mice via suppressing inflammatory pathways [ 10 , 11 ]. Moreover, oridonin attenuated diabetes-associated renal inflammation and injury in rats [ 12 ], suggesting that the compound has a protective action against both acute and chronic kidney injury.…”

Oridonin Protects against Myocardial Ischemia–Reperfusion Injury by Inhibiting GSDMD-Mediated Pyroptosis

“…Currently, there is mounting evidence that oridonin can inhibit I/R injury, including injury to the myocardium, lower limbs, brain tissue, and kidney, by downregulating oxidative stress and NLRP3-mediated inflammatory pathways [ 9 , 23 , 24 ]. Although these studies have included metabolomics, exosomes, Mincle, and NF-κB, none of the mechanisms have clarified the key role of GSDMD-mediated pyroptosis [ 25 , 26 , 27 ]. In our study, treatment with H/R and oridonin did not alter the expression of GSDMD-FL.…”