scutellarein and Ischemia

Acute kidney injury (AKI) is a clinical syndrome that usually caused by ischemia/reperfusion (I/R). Previous studies have revealed the protection of scutellarein against ischemia in nervous system. This study aimed to demonstrate the potential of scutellarein in ischemic AKI.. Animal model of ischemic AKI was established by clamping bilateral kidney pedicles in Sprague-Dawley rats. HK-2 cells were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) to induce a cell model of AKI. The effects of scutellarein pre-treatment were detected by H&E staining, TUNEL, ELISA, CCK-8, LDH activity assay, ROS generation, flow cytometry, qRT-PCR and western blotting. Bioinformatic analysis was performed to probe the targets of scutellarein.. The blood urea nitrogen (BUN) and serum creatinine (SCr) levels in rats treated with scutellarein were lower than that in model groups. Scutellarein suppressed the pathological injury of kidney, and dose-dependently inhibited the apoptosis and pro-inflammatory cytokines release (IL-1β, IL-6 and IL-18). Scutellarein prevented OGD/R-induced HK-2 cell loss and cytotoxicity. ROS generation, apoptosis, and inflammation induced by OGD/R were all inhibited by scutellarein. By searching on the TCMSP and Symmap databases, COX-2 was screened out as a target of scutellarein. Scutellarein has no significant impacts on COX-2 mRNA expression, but could inhibit its protein level. Scutellarein promoted COX-2 protein degradation via enhancing autophagy. Furthermore, overexpression of COX-2 partly eliminated the renal protection of scutellarein in HK-2 cells.. Scutellarein was suggested as a renal protective agent against ischemia-induced damage in AKI. The protective properties of scutellarein may be through inhibition of COX-2.

Topics: Acute Kidney Injury; Animals; Apigenin; Cell Death; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Inflammation; Ischemia; Kidney Tubules, Proximal; Male; Rats; Rats, Sprague-Dawley

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, it is very difficult to obtain scutellarein in nature compared with scutellarin. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. The in vitro antioxidant activities of scutellarein were evaluated by measuring its scavenging capacities toward DPPH, ABTS(+•), (•)OH free radicals and its protective effect on H(2)O(2)-induced cytotoxicity in PC12 cells using MTT assay method. The results showed that essential point to the synthesis was the implementation of H(2)SO(4) in 90% ethanol in N(2) atmosphere; scutellarein had stronger antioxidant activity than scutellarin. The results have laid the foundation for further research and the development of scutellarein as a promising candidate for ischemic cerebrovascular disease.

Topics: Animals; Apigenin; Benzothiazoles; Biphenyl Compounds; Cell Survival; Cerebrovascular Disorders; Free Radical Scavengers; Glucuronates; Hydrogen Peroxide; Ischemia; PC12 Cells; Picrates; Rats; Sulfonic Acids