Protective effect of hypoglycemic granule against diabetes‐induced liver injury by alleviating glycolipid metabolic disorder and oxidative stress

Abstract The current study was designed to explore the therapeutic effect and mechanism of different extraction, which came from hypoglycemic granule on diabetes‐induced liver injury. The ethanol fraction (HGEF) and aqueous fraction (HGAF) from hypoglycemic granule were prepared and administered p.o. to diabetic mice for 17 weeks after 6 weeks of constructing the model. Hematoxylin‐eosin (HE) staining and periodic acid‐Schiff (PAS) staining were individually applied to observe the morphological change and glycogen deposition. In addition, Oil Red O staining was adopted in lipid droplets detection. Western blot analysis was performed to evaluate the protein expression. The commercial biochemical kits were used to determine the fasting blood glucose value, enzyme activity, and some biochemical indicators. HGEF not only significantly decreased the levels of blood glucose, the content of triglycerides, total cholesterol, low‐density lipoprotein, and lipid droplet accumulation, but also remarkably enhanced the high‐density lipoprotein, glycogen synthesis, and further improved the hepatic function in diabetic mice. Moreover, HGEF increased the superoxide dismutase (SOD) activity and inhibited the malondialdehyde production, so did HGAF. HGAF performed potential to modulate lipid metabolism via decreasing TG and LDL levels. Further, the protein expressions of SOD, nuclear factor erythroid 2‐related factor 2 (Nrf2), and forkhead box O3 (Foxo3a) were increased by HGEF, whereas the receptor‐interacting serine‐threonine kinase 3 (RIP3), calcium/calmodulin‐dependent protein kinase II (CaMKII), and cytochrome c (Cyt c ) expressions were inhibited. Our present results suggest that HGEF has superiority in ameliorating oxidative stress via modulating hepatic glycolipid metabolism homeostasis in low‐dose streptozotocin‐induced liver tissue of diabetic mice.