Nano-Stevia reduces the liver injury caused by streptozotocin (STZ)-induced diabetes in rats by targeting PEPCK/GCK genes, INSR pathway and apoptosis.

OBJECTIVES: Extensive application of stevia in the treatment of type 2 diabetes mellitus (DM) has been proven by a large number of previous studies. We prepared stevia loaded in nanoniosomes (nanostevia) to improve its bioavailability, functionality, and stability and explore its protective effects and underlying mechanisms in the liver of STZ-induced diabetic rats.

METHODS: Single-dose intraperitoneal injection of STZ (50 mg/kg body weight) was used to establish diabetic model. The mRNA levels of PEPCK and GCK genes and the protein level of INSR were evaluated by Real time-PCR and Western blot assays, respectively. TUNEL assay was used to detect apoptotic cell death in the liver tissue.

RESULTS: Diabetic rats exhibited significantly reduced levels of INSR (*** P < 0.001) as well as elevated levels of PEPCK (*** P < 0.001). Both stevia and nano-stevia were capable of increasing levels of GCK and INSR and reducing levels of PEPCK (## P < 0.01 and ### P < 0.001, respectively). In addition, significantly increased number of apoptotic cell death was seen in the liver tissue of diabetic rats (*** P < 0.001) which was markedly mitigated by treatment with both Stevia and nano-Stevia (#P < 0.05 and ## P < 0.01, respectively).

CONCLUSION: Both stevia and nano-stevia demonstrates potent anti-apoptotic activity in the liver tissue of diabetic rats by targeting PEPCK/GCK genes and INSR pathway. These finding show that nano-stevia has more potential to reduce the liver injury caused by STZ-induced diabetes in rats and hence can be considered a valid agent and alternative therapy for attenuating complications of type 2 DM.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01278-2.