Nano-Stevia Attenuates the Liver Injury in STZ-Induced Diabetes by Targeting Hepatic Glucose Transporter GLUT-2/GLUT-9

Better activity and safety of bioactive phytochemicals from medicinal plants make them excellent candidates for treatment of diabetes mellitus (DM). In order to improve bioavailability, functionality, and stability, we prepared stevia loaded in nano-niosomes (nano-stevia) to explore its protective effects against the liver injury caused by streptozotocin (STZ)-induced diabetes in rats. In order to induce STZ-induced diabetic model in male Wistar rats, a single dose of a freshly prepared solution of STZ (50 mg/kg body weight) was intraperitoneally injected. Real-time PCR was used to investigate the mRNA levels of pro-inflammatory cytokines and GLUT‐2/9 genes. Oxidative stress factors, liver damage, and hepatic fibrosis were assessed using ELISA assay, hematoxylin and eosin (H&E), and Masson trichrome staining. Our in vivo analysis revealed that STZ-induced diabetic rats exhibited elevated levels of pro-inflammatory cytokines including TNF-α (* P < 0.05) and IL-6 (*** P < 0.001) reduced SOD and CAT activities (*** P < 0.001), elevated MDA levels (* P < 0.01), live damage, and hepatic fibrosis (*** P < 0.001) that reversed by both stevia and nano-stevia. Moreover, both stevia and nano-stevia significantly increased the mRNA levels of GLUT‐2/9 genes ((## P < 0.01 and ### P < 0.001, respectively). Altogether, this study provides evidence of antidiabetic and anti-inflammatory activities of nano-stevia by targeting hepatic glucose transporter GLUT-2/ GLUT-9. Our findings demonstrate that nano-stevia can be considered an excellent candidate and alternative therapy to reduce the liver injury caused by STZ-induced diabetes in rats.