shikonin and Diabetic-Nephropathies

In diabetes mellitus, diabetic nephropathy (DN) is a typical complication and pivotal cause of chronic kidney disease. The DN disease burden is among the highest in the world and is associated with high morbidity, mortality, and disease burden. Safe and effective medications are urgently needed for the treatment of DN. Interest has been increasing in Shikonin, extracted from the naphthoquinone plant, particularly in determining its renal protective effect.. In this study, we explored Shikonin's effects and potential mechanisms on a streptozotocin (STZ)-induced DN experimental model. An STZ-induced rat diabetic model was established, and the rats were treated with different doses of Shikonin (10/50 mg/kg) for 4 weeks. Blood, urine, and renal tissue samples were collected after the last administration. Renal tissues were examined to detect each group's physiologic, biochemical, histopathologic, and molecular changes.. The results showed that Shikonin administration could significantly alleviate the STZ-induced elevation of blood urea nitrogen, serum creatinine, urinary protein content, and renal pathologic injury. Furthermore, Shikonin significantly decreased oxidative stress, inflammation, and Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB expression levels in DN kidney tissues. Shikonin showed a dose-dependent effect, with the best outcome at 50 mg/kg.. Shikonin could effectively alleviate DN-related nephropathy damage and reveal the underlying pharmacologic mechanism. Based on the results, a Shikonin combination can be used in clinical treatment.

Topics: Albuminuria; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Urea Nitrogen; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Male; Naphthoquinones; Oxidative Stress; Rats; Rats, Sprague-Dawley; Streptozocin

Hyperglycemia-induced oxidative stress is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). Treating high-glucose (HG)-induced proximal tubule injury has become a patential therapeutic option to attenuate the onset and progression of DN. The present study aimed to investigate the renoprotective effect of shikonin, the chief active compound extracted from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on HG-induced cytotoxicity in NRK-52E cells. Treating cells with HG significantly reduce cell viability while also significantly increasing content of reactive oxygen species (ROS). Treating the cells with shikonin improved these changes induced by HG. Shikonin strongly stabilized mitochondrial membrane potential in HG-induced NRK-52E cells. In addition, treatment with shikonin upregulated antioxidant system in response to ROS by increasing levels of SOD and CAT. Furthermore, shikonin also strongly decreased the levels of activated caspase-3, Bax and p-GSK-3β while increased the p-AKT level. These findings provide that the renoprotective effects of shikonin against HG-induced cytotoxicity in NRK-52E cells may be mediated in inhibiting oxidative stress through activating of the AKT signalling pathway.

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Cell Line; Cell Survival; Diabetic Nephropathies; Epithelial Cells; Glucose; Glycogen Synthase Kinase 3 beta; Kidney Tubules, Proximal; Membrane Potential, Mitochondrial; Naphthoquinones; Oxidative Stress; Protective Agents; Rats; Reactive Oxygen Species; Signal Transduction