Atractylenolide-1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/c-kit signaling pathway

Abstract

Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in Sprague-Dawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide-1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peri- stalsis and gastric blood flow. Compared with the DGP group, atractylenolide-1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZ-induced group compared with the vehicle control group. Moreover, the STZ-induced group displayed downregulated expression levels of the DGP indicator KIT proto-oncogene, receptor tyrosine kinase (c-kit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stress-related markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide-1 significantly coun- teracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZ-induced DGP model rats. Further research indicated that atractylenolide-1 regulated oxidative stress reactions and improved gastric function by activating the SCF/c-kit signaling pathway. Collectively, the results of the present study suggested that atractylenolide-1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/c-kit signaling pathway, providing novel insights for the treatment of DGP.