Abstract
Previous studies have demonstrated that TWA, a Chinese herbal medicine, could significantly improve the symptoms of patients with diabetic gastrointestinal dysfunction. However, the specific mechanism of regulating intestinal peristalsis has not been found. This study aimed to discover TWA's therapeutic mechanism for regulating intestinal motility. The intestinal propulsion rate of diabetic rats was significantly increased after treatment with TWA for 8 weeks. Aiming at the mechanical structure, biomechanical testing indicated that TWA can significantly decrease the no-load intestinal wall thickness, cross-sectional area, and angular spread in a zero-stress state. Notably, intestinal stress-strain curve shifted to the right, which indicated TWA can inhibit intestinal hyperplasia and hardening and improve biomechanical remodeling. Further study of the mechanism revealed that TWA significantly inhibited the expression of AGE in the villi, crypt, and muscle and RAGE in crypt and upregulated the expression of nerve regulator (PSD95, C-kit and SCF). Radioimmunoassay showed TWA treatment decreased levels of serum somatostatin and vasoactive intestinal peptide. Moreover, associations were found between the intestinal propulsion rate with the morphologic and biomechanical remodeling parameters, changes of nerve factors, and endocrine hormones. Morphologic and biomechanical remodeling of the intestinal wall are the pathologic basis of gastrointestinal dysfunction. TWA can benefit intestinal motility by improving biomechanical and morphologic remodeling and by regulating expression of neuroendocrine factors. The results showed that the effect of TWA was dose-dependent, the higher the dose, the greater is the improvement. Thus, traditional Chinese medicine might be a valuable tool for treating diabetic gastrointestinal dysfunction.