Protective effect of Hachimi-jio-gan against the development of pancreatic fibrosis and oxidative damage in Otsuka Long-Evans Tokushima Fatty rats

In our previous study, the polyherbal drug Hachimi-jio-gan was reported to possess a protective effect against the progression of diabetic nephropathy by attenuating glucose toxicity and renal damage with a type 2 diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Based on these findings, this study was undertaken to reveal the effect of Hachimi-jio-gan on pancreatic damage focusing on fibrosis and oxidative stress in type 2 diabetes. OLETF rats were orally administered Hachimi-jio-gan for 32 weeks, and we assessed the changes in the serum glucose level every 8 weeks, as well as those of body weight, and food and water consumption every 4 weeks. In addition, pancreatic wet weight, insulin content, and Western blot analyses of transforming growth factor-β1, fibronectin, and nuclear factor-κB-related inflammatory enzymes, such as inducible nitric oxide synthesis and cyclooxygenase-2, were also performed in the pancreas. As a consequence, long-term treatment with Hachimi-jio-gan had a hypoglycemic effect, reducing pancreatic atrophy and fibrosis, and ameliorating the oxidative status. Therefore, this may provide evidence that Hachimi-jio-gan is a therapeutic target for preventing the development of pancreatic damage concomitant with hyperglycemia in type 2 diabetes.