Cabozantinib is a tyrosine kinase inhibitor with anti-tumor activity in kidney cancer. However, the efficacy of cabozantinib in other renal diseases has never been reported. Here, we focused on exploring the effect of cabozantinib on diabetic nephropathy (DN). The biofunctions of cabozantinib in human renal glomerular endothelial cells (hGECs) under high glucose conditions have been investigated. We found that cabozantinib ameliorated high glucose-induced oxidative stress in hGECs with decreased production of mitochondrial reactive oxygen species (ROS) and increased glutathione peroxidase (GSH-PX) activity. Cabozantinib ameliorated high glucose-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the production of nitric oxide (NO) in hGECs. It also suppressed the expression of pro-inflammatory mediators, interleukin-6 (IL-6) and monocyte chemokine protein 1 (MCP-1), against high glucose exposure in hGECs. Cabozantinib reduced the expression of early growth response-1 (Egr-1) in high glucose-treated hGECs, while Egr-1 overexpression abolished the protective effects of cabozantinib against high glucose in hGECs. In conclusion, cabozantinib protected hGECs from high glucose-induced oxidative stress, NO deficiency, and inflammation via regulating Egr-1. These findings suggest that cabozantinib might be used as an adjuvant to control DN.

Background Osteoporosis is a progressive bone disease, which is characterized by high bone resorption, and low bone density and mass. Osteoporosis elevates the risk of bone fragility and fracture, which leads to significant morbidity and poor life quality. Objectives The current study focuses to explore the anti-osteoporosis activity of cynaropicrin against the ovariectomized (OVX)-induced osteoporosis in rats. Methodology The OVX method was performed on the female rats to induce osteoporosis and then treated with 10 and 20 mg/kg of cynaropicrin, respectively, for 16 weeks. The uterus and femur tissues were excised from rats after the sacrification. The biomechanical properties of femur bones were analyzed to detect the stiffness, maximum load, young modulus, and energy absorption. The levels of acid phosphatase (ACP), bone-gla-protein (BGP), and estradiol (E2) in the serum were analyzed. The status of TNF-α, IL-6, IL-1β, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) was analyzed in the serum samples of experimental rats. The femur tissues were examined by histopathological analysis. Results The cynaropicrin treatment effectively increased the uterine and femoral weight in the OVX rats. The stiffness, maximum load, young modulus, energy, and femoral length were effectively increased by the cynaropicrin treatment. Cynaropicrin decreased the levels of BGP and ACP and increased the E2 level. The Cr, Ca, and P levels were appreciably increased and TNF-α, IL-6 and IL-1β levels were decreased by cynaropicrin on the OVX rats. The cynaropicrin treatment also increased the OPG and reduced the RANKL in the OVX rats. The histological findings revealed that cynaropicrin improved the femur trabecular bone microarchitecture in the OVX rats. Conclusion Our findings revealed that cynaropicrin increased the femoral weight and length, restored bone turnover markers and mineral profiles, and decreased inflammatory markers.