Chaihu Shugan San promotes gastric motility in rats with functional dyspepsia by regulating Drp-1-mediated ICC mitophagy.

Context: Chaihu Shugan San (CHSGS) was effective in the treatment of functional dyspepsia (FD).

Objective: To investigate the mechanism of CHSGS in FD through dynamin-related protein 1 (Drp-1)-mediated interstitial cells of cajal (ICC) mitophagy.

Materials and methods: Forty Sprague-Dawley (SD) rats were randomly divided into control, model, mdivi-1, mdivi-1 + CHSGS and CHSGS groups. Tail-clamping stimulation was used to establish the FD model. Mdivi-1 + CHSGS and CHSGS groups were given CHSGS aqueous solution (4.8 g/kg) by gavage twice a day. Mdivi-1 (25 mg/kg) was injected intraperitoneally once every other week for 4 w. Mitochondrial damage was observed by corresponding kits and related protein expressions were assessed by Immunofluorescence and (or) Western Blot.

Results: Compared with the mean value of the control group, superoxide dismutase (SOD) and citrate synthase (CS) in the model group were decreased by 11% and 35%; malondialdehyde (MDA) and reactive oxygen species (ROS) were increased by 1.2- and 2.8-times; ckit fluorescence and protein expressions were decreased by 85% and 51%, co-localization expression of LC3 and voltage dependent anion channel 1 (VDAC1), Drp-1 and translocase of the outer mitochondrial membrane 20 (Tom20) were increased by 10.1- and 5.4-times; protein expressions of Drp-1, Beclin-1, and LC3 were increased by 0.5-, 1.4-, and 2.5-times whereas p62 was decreased by 43%. After mdivi-1 and (or) CHSGS intervention, the above situation has been improved.

Discussion and conclusion: CHSGS could improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp-1-mediated ICC mitophagy.